WorldWideScience

Sample records for automatic target selection

  1. Physics of Automatic Target Recognition

    CERN Document Server

    Sadjadi, Firooz

    2007-01-01

    Physics of Automatic Target Recognition addresses the fundamental physical bases of sensing, and information extraction in the state-of-the art automatic target recognition field. It explores both passive and active multispectral sensing, polarimetric diversity, complex signature exploitation, sensor and processing adaptation, transformation of electromagnetic and acoustic waves in their interactions with targets, background clutter, transmission media, and sensing elements. The general inverse scattering, and advanced signal processing techniques and scientific evaluation methodologies being used in this multi disciplinary field will be part of this exposition. The issues of modeling of target signatures in various spectral modalities, LADAR, IR, SAR, high resolution radar, acoustic, seismic, visible, hyperspectral, in diverse geometric aspects will be addressed. The methods for signal processing and classification will cover concepts such as sensor adaptive and artificial neural networks, time reversal filt...

  2. Unification of automatic target tracking and automatic target recognition

    Science.gov (United States)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  3. The Automatic Measurement of Targets

    DEFF Research Database (Denmark)

    Höhle, Joachim

    1997-01-01

    The automatic measurement of targets is demonstrated by means of a theoretical example and by an interactive measuring program for real imagery from a réseau camera. The used strategy is a combination of two methods: the maximum correlation coefficient and the correlation in the subpixel range. F...... interactive software is also part of a computer-assisted learning program on digital photogrammetry....

  4. Research on Automatic Target Tracking Based on PTZ System

    Directory of Open Access Journals (Sweden)

    Ni Zhang

    2012-11-01

    Full Text Available This paper studies an algorithm of automatic target tracking based on PTZ system. Select the tracking target and set up the target motion trajectory in the video screen. Along the motion trajectory, the system controls the PTZ rotation automatically to track the target real-timely. At the same time, it adjusts the zoom to enlarge or reduce to make sure the target can display on the video screen center clearly at the suitable size. By testing on groups of video, verify the effectiveness of the automatic target tracking algorithm.

  5. Self-assessing target with automatic feedback

    Science.gov (United States)

    Larkin, Stephen W.; Kramer, Robert L.

    2004-03-02

    A self assessing target with four quadrants and a method of use thereof. Each quadrant containing possible causes for why shots are going into that particular quadrant rather than the center mass of the target. Each possible cause is followed by a solution intended to help the marksman correct the problem causing the marksman to shoot in that particular area. In addition, the self assessing target contains possible causes for general shooting errors and solutions to the causes of the general shooting error. The automatic feedback with instant suggestions and corrections enables the shooter to improve their marksmanship.

  6. Automatic target tracking in FLIR image sequences

    Science.gov (United States)

    Bal, Abdullah; Alam, Mohammad S.

    2004-09-01

    Moving target tracking is a challenging task and is increasingly becoming important for various applications. In this paper, we have presented target detection and tracking algorithm based on target intensity feature relative to surrounding background, and shape information of target. Proposed automatic target tracking algorithm includes two techniques: intensity variation function (IVF) and template modeling (TM). The intensity variation function is formulated by using target intensity feature while template modeling is based on target shape information. The IVF technique produces the maximum peak value whereas the reference target intensity variation is similar to the candidate target intensity variation. When IVF technique fails, due to background clutter, non-target object or other artifacts, the second technique, template modeling, is triggered by control module. By evaluating the outputs from the IVF and TM techniques, the tracker determines the real coordinates of the target. Performance of the proposed ATT is tested using real life forward-looking infrared (FLIR) image sequences taken from an airborne, moving platform.

  7. Automatic Algorithm Selection for Complex Simulation Problems

    CERN Document Server

    Ewald, Roland

    2012-01-01

    To select the most suitable simulation algorithm for a given task is often difficult. This is due to intricate interactions between model features, implementation details, and runtime environment, which may strongly affect the overall performance. An automated selection of simulation algorithms supports users in setting up simulation experiments without demanding expert knowledge on simulation. Roland Ewald analyzes and discusses existing approaches to solve the algorithm selection problem in the context of simulation. He introduces a framework for automatic simulation algorithm selection and

  8. Robust automatic target recognition in FLIR imagery

    Science.gov (United States)

    Soyman, Yusuf

    2012-05-01

    In this paper, a robust automatic target recognition algorithm in FLIR imagery is proposed. Target is first segmented out from the background using wavelet transform. Segmentation process is accomplished by parametric Gabor wavelet transformation. Invariant features that belong to the target, which is segmented out from the background, are then extracted via moments. Higher-order moments, while providing better quality for identifying the image, are more sensitive to noise. A trade-off study is then performed on a few moments that provide effective performance. Bayes method is used for classification, using Mahalanobis distance as the Bayes' classifier. Results are assessed based on false alarm rates. The proposed method is shown to be robust against rotations, translations and scale effects. Moreover, it is shown to effectively perform under low-contrast objects in FLIR images. Performance comparisons are also performed on both GPU and CPU. Results indicate that GPU has superior performance over CPU.

  9. SETI target selection.

    Science.gov (United States)

    Latham, D. W.; Soderblom, D. R.

    1995-06-01

    The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. The authors propose strategies for target selection with two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar-type stars, and to minimize the chances of missing signals from unexpected sites.

  10. Towards Automatic Decentralized Control Structure Selection

    DEFF Research Database (Denmark)

    Jørgensen, John Bagterp; Jørgensen, Sten Bay

    2000-01-01

    A subtask in integration of design and control of chemical processes is the selection of a control structure. Automating the selection of the control structure enables sequential integration of process and control design. As soon as the process is specified or computed, a structure for...... decentralized control is determined automatically, and the resulting decentralized control structure is automatically tuned using standard techniques. Dynamic simulation of the resulting process system gives immediate feedback to the process design engineer regarding practical operability of the process. The...... control structure selection problem is formulated as a special MILP employing cost coefficients which are computed using Parseval's theorem combined with RGA and IMC concepts. This approach enables selection and tuning of large-scale plant-wide decentralized controllers through efficient combination of...

  11. Towards Automatic Decentralized Control Structure Selection

    DEFF Research Database (Denmark)

    A subtask in integration of design and control of chemical processes is the selection of a control structure. Automating the selection of the control structure enables sequential integration of process and controld esign. As soon as the process is specified or computed, a structure for...... decentralized control is determined automatically, and the resulting decentralized control structure is automatically tuned using standard techniques. Dynamic simulation of the resulting process system gives immediate feedback to the process design engineer regarding practical operability of the process. The...... control structure selection problem is formulated as a special MILP employing cost coefficients which are computed using Parseval's theorem combined with RGA and IMC concepts. This approach enables selection and tuning of large-scale plant-wide decentralized controllers through efficient combination of...

  12. Channel selection for automatic seizure detection

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Kjaer, Troels Wesenberg; Madsen, Rasmus Elsborg; Remvig, Line Sofie; Thomsen, Carsten Eckhart; Sørensen, Helge Bjarup Dissing

    2012-01-01

    Objective: To investigate the performance of epileptic seizure detection using only a few of the recorded EEG channels and the ability of software to select these channels compared with a neurophysiologist. Methods: Fifty-nine seizures and 1419 h of interictal EEG are used for training and testing...... of an automatic channel selection method. The characteristics of the seizures are extracted by the use of a wavelet analysis and classified by a support vector machine. The best channel selection method is based upon maximum variance during the seizure. Results: Using only three channels, a seizure...... recorded directly on the epileptic focus. Conclusions: Based on our dataset, automatic seizure detection can be done using only three EEG channels without loss of performance. These channels should be selected based on maximum variance and not, as often done, using the focal channels. Significance: With...

  13. Automatic target recognition apparatus and method

    Energy Technology Data Exchange (ETDEWEB)

    Baumgart, Chris W. (Santa Fe, NM); Ciarcia, Christopher A. (Los Alamos, NM)

    2000-01-01

    An automatic target recognition apparatus (10) is provided, having a video camera/digitizer (12) for producing a digitized image signal (20) representing an image containing therein objects which objects are to be recognized if they meet predefined criteria. The digitized image signal (20) is processed within a video analysis subroutine (22) residing in a computer (14) in a plurality of parallel analysis chains such that the objects are presumed to be lighter in shading than the background in the image in three of the chains and further such that the objects are presumed to be darker than the background in the other three chains. In two of the chains the objects are defined by surface texture analysis using texture filter operations. In another two of the chains the objects are defined by background subtraction operations. In yet another two of the chains the objects are defined by edge enhancement processes. In each of the analysis chains a calculation operation independently determines an error factor relating to the probability that the objects are of the type which should be recognized, and a probability calculation operation combines the results of the analysis chains.

  14. Automatic learning-based beam angle selection for thoracic IMRT

    Energy Technology Data Exchange (ETDEWEB)

    Amit, Guy; Marshall, Andrea [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2M9 (Canada); Purdie, Thomas G., E-mail: tom.purdie@rmp.uhn.ca; Jaffray, David A. [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2M9 (Canada); Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5S 3E2 (Canada); Techna Institute, University Health Network, Toronto, Ontario M5G 1P5 (Canada); Levinshtein, Alex [Department of Computer Science, University of Toronto, Toronto, Ontario M5S 3G4 (Canada); Hope, Andrew J.; Lindsay, Patricia [Radiation Medicine Program, Princess Margaret Cancer Centre, Toronto, Ontario M5G 2M9, Canada and Department of Radiation Oncology, University of Toronto, Toronto, Ontario M5S 3E2 (Canada); Pekar, Vladimir [Philips Healthcare, Markham, Ontario L6C 2S3 (Canada)

    2015-04-15

    Purpose: The treatment of thoracic cancer using external beam radiation requires an optimal selection of the radiation beam directions to ensure effective coverage of the target volume and to avoid unnecessary treatment of normal healthy tissues. Intensity modulated radiation therapy (IMRT) planning is a lengthy process, which requires the planner to iterate between choosing beam angles, specifying dose–volume objectives and executing IMRT optimization. In thorax treatment planning, where there are no class solutions for beam placement, beam angle selection is performed manually, based on the planner’s clinical experience. The purpose of this work is to propose and study a computationally efficient framework that utilizes machine learning to automatically select treatment beam angles. Such a framework may be helpful for reducing the overall planning workload. Methods: The authors introduce an automated beam selection method, based on learning the relationships between beam angles and anatomical features. Using a large set of clinically approved IMRT plans, a random forest regression algorithm is trained to map a multitude of anatomical features into an individual beam score. An optimization scheme is then built to select and adjust the beam angles, considering the learned interbeam dependencies. The validity and quality of the automatically selected beams evaluated using the manually selected beams from the corresponding clinical plans as the ground truth. Results: The analysis included 149 clinically approved thoracic IMRT plans. For a randomly selected test subset of 27 plans, IMRT plans were generated using automatically selected beams and compared to the clinical plans. The comparison of the predicted and the clinical beam angles demonstrated a good average correspondence between the two (angular distance 16.8° ± 10°, correlation 0.75 ± 0.2). The dose distributions of the semiautomatic and clinical plans were equivalent in terms of primary target volume

  15. Automatic learning-based beam angle selection for thoracic IMRT

    International Nuclear Information System (INIS)

    Purpose: The treatment of thoracic cancer using external beam radiation requires an optimal selection of the radiation beam directions to ensure effective coverage of the target volume and to avoid unnecessary treatment of normal healthy tissues. Intensity modulated radiation therapy (IMRT) planning is a lengthy process, which requires the planner to iterate between choosing beam angles, specifying dose–volume objectives and executing IMRT optimization. In thorax treatment planning, where there are no class solutions for beam placement, beam angle selection is performed manually, based on the planner’s clinical experience. The purpose of this work is to propose and study a computationally efficient framework that utilizes machine learning to automatically select treatment beam angles. Such a framework may be helpful for reducing the overall planning workload. Methods: The authors introduce an automated beam selection method, based on learning the relationships between beam angles and anatomical features. Using a large set of clinically approved IMRT plans, a random forest regression algorithm is trained to map a multitude of anatomical features into an individual beam score. An optimization scheme is then built to select and adjust the beam angles, considering the learned interbeam dependencies. The validity and quality of the automatically selected beams evaluated using the manually selected beams from the corresponding clinical plans as the ground truth. Results: The analysis included 149 clinically approved thoracic IMRT plans. For a randomly selected test subset of 27 plans, IMRT plans were generated using automatically selected beams and compared to the clinical plans. The comparison of the predicted and the clinical beam angles demonstrated a good average correspondence between the two (angular distance 16.8° ± 10°, correlation 0.75 ± 0.2). The dose distributions of the semiautomatic and clinical plans were equivalent in terms of primary target volume

  16. Automatic target validation based on neuroscientific literature mining for tractography

    Directory of Open Access Journals (Sweden)

    Xavier Vasques

    2015-05-01

    Full Text Available Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so that they can be used for anatomical connection studies and more specifically for tractography. We applied text-mining models to three structures: two well studied structures, since validated deep brain stimulation targets, the internal globus pallidus and the subthalamic nucleus and, the nucleus accumbens, an exploratory target for treating psychiatric disorders. We performed a systematic review of the literature to document the projections of the three selected structures and compared it with the targets proposed by text-mining models, both in rat and primate (including human. We ran probabilistic tractography on the nucleus accumbens and compared the output with the results of the text-mining models and literature review. Overall, text-mining the literature could find three times as many targets as two man-weeks of curation could. The overall efficiency of the text-mining against literature review in our study was 98% recall (at 36% precision, meaning that over all the targets for the three selected seeds, only one target has been missed by text-mining. We demonstrate that connectivity for a structure of interest can be extracted from a very large amount of publications and abstracts. We believe this tool will be useful in helping the neuroscience community to facilitate connectivity studies of particular brain regions. The text mining tools used for the study are part of the HBP Neuroinformatics Platform, publicly available at http://connectivity-brainer.rhcloud.com/.

  17. Automatic Target Detection by Optimal Morphological Filters

    Institute of Scientific and Technical Information of China (English)

    YU Nong(余农); WU Hao(吴昊); WU ChangYong(吴常泳); LI YuShu(李予蜀)

    2003-01-01

    It is widely accepted that the design of morphological filters, which are optimal in some sense, is a difficult task. In this paper a novel method for optimal learning of morphological filtering parameters (Genetic training algorithm for morphological filters, GTAMF) is presented.GTAMF adopts new crossover and mutation operators called the curved cylinder crossover and master-slave mutation to achieve optimal filtering parameters in a global searching. Experimental results show that this method is practical, easy to extend, and markedly improves the performances of morphological filters. The operation of a morphological filter can be divided into two basic problems including morphological operation and structuring element (SE) selection. The rules for morphological operations are predefined so that the filter's properties depend merely on the selection of SE. By means of adaptive optimization training, structuring elements possess the shape and structural characteristics of image targets, and give specific information to SE. Morphological filters formed in this way become certainly intelligent and can provide good filtering results and robust adaptability to image targets with clutter background.

  18. Automatic target extraction in complicated background for camera calibration

    Science.gov (United States)

    Guo, Xichao; Wang, Cheng; Wen, Chenglu; Cheng, Ming

    2016-03-01

    In order to perform high precise calibration of camera in complex background, a novel design of planar composite target and the corresponding automatic extraction algorithm are presented. Unlike other commonly used target designs, the proposed target contains the information of feature point coordinate and feature point serial number simultaneously. Then based on the original target, templates are prepared by three geometric transformations and used as the input of template matching based on shape context. Finally, parity check and region growing methods are used to extract the target as final result. The experimental results show that the proposed method for automatic extraction and recognition of the proposed target is effective, accurate and reliable.

  19. Gaussian process classification using automatic relevance determination for SAR target recognition

    Science.gov (United States)

    Zhang, Xiangrong; Gou, Limin; Hou, Biao; Jiao, Licheng

    2010-10-01

    In this paper, a Synthetic Aperture Radar Automatic Target Recognition approach based on Gaussian process (GP) classification is proposed. It adopts kernel principal component analysis to extract sample features and implements target recognition by using GP classification with automatic relevance determination (ARD) function. Compared with k-Nearest Neighbor, Naïve Bayes classifier and Support Vector Machine, GP with ARD has the advantage of automatic model selection and hyper-parameter optimization. The experiments on UCI datasets and MSTAR database show that our algorithm is self-tuning and has better recognition accuracy as well.

  20. Automatic targeting of plasma spray gun

    International Nuclear Information System (INIS)

    A means for monitoring the material portion in the flame of a plasma spray gun during spraying operations is described. A collimated detector, sensitive to certain wavelengths of light emission, is used to locate the centroid of the material with each pass of the gun. The response from the detector is then relayed to the gun controller to be used to automatically realign the gun

  1. Automatic targeting of plasma spray gun

    Science.gov (United States)

    Abbatiello, Leonard A.; Neal, Richard E.

    1978-01-01

    A means for monitoring the material portion in the flame of a plasma spray gun during spraying operations is provided. A collimated detector, sensitive to certain wavelengths of light emission, is used to locate the centroid of the material with each pass of the gun. The response from the detector is then relayed to the gun controller to be used to automatically realign the gun.

  2. Automatic target validation based on neuroscientific literature mining for tractography

    OpenAIRE

    Xavier Vasques; Renaud Richardet; Etienne Pralong; LAURA CIF

    2015-01-01

    Target identification for tractography studies requires solid anatomical knowledge validated by an extensive literature review across species for each seed structure to be studied. Manual literature review to identify targets for a given seed region is tedious and potentially subjective. Therefore, complementary approaches would be useful. We propose to use text-mining models to automatically suggest potential targets from the neuroscientific literature, full-text articles and abstracts, so t...

  3. High Range Resolution Profile Automatic Target Recognition Using Sparse Representation

    Institute of Scientific and Technical Information of China (English)

    Zhou Nuo; Chen Wei

    2010-01-01

    Sparse representation is a new signal analysis method which is receiving increasing attention in recent years.In this article,a novel scheme solving high range resolution profile automatic target recognition for ground moving targets is proposed.The sparse representation theory is applied to analyzing the components of high range resolution profiles and sparse coefficients are used to describe their features.Numerous experiments with the target type number ranging from 2 to 6 have been implemented.Results show that the proposed scheme not only provides higher recognition preciseness in real time,but also achieves more robust performance as the target type number increases.

  4. System for automatic x-ray-image analysis, measurement, and sorting of laser fusion targets

    International Nuclear Information System (INIS)

    This paper describes the Automatic X-Ray Image Analysis and Sorting (AXIAS) system which is designed to analyze and measure x-ray images of opaque hollow microspheres used as laser fusion targets. The x-ray images are first recorded on a high resolution film plate. The AXIAS system then digitizes and processes the images to accurately measure the target parameters and defects. The primary goals of the AXIAS system are: to provide extremely accurate and rapid measurements, to engineer a practical system for a routine production environment and to furnish the capability of automatically measuring an array of images for sorting and selection

  5. Automatic Parameters Selection for SVM Based on PSO

    Institute of Scientific and Technical Information of China (English)

    ZHANG Mingfeng; ZHU Yinghua; ZHENG Xu; LIU Yu

    2007-01-01

    Motivated by the fact that automatic parameters selection for Support Vector Machine (SVM) is an important issue to make SVM practically useful and the common used Leave-One-Out (LOO) method is complex calculation and time consuming,an effective strategy for automatic parameters selection for SVM is proposed by using the Particle Swarm Optimization (PSO) in this paper.Simulation results of practice data model demonstrate the effectiveness and high efficiency of the proposed approach.

  6. Radar automatic target recognition (ATR) and non-cooperative target recognition (NCTR)

    CERN Document Server

    Blacknell, David

    2013-01-01

    The ability to detect and locate targets by day or night, over wide areas, regardless of weather conditions has long made radar a key sensor in many military and civil applications. However, the ability to automatically and reliably distinguish different targets represents a difficult challenge. Radar Automatic Target Recognition (ATR) and Non-Cooperative Target Recognition (NCTR) captures material presented in the NATO SET-172 lecture series to provide an overview of the state-of-the-art and continuing challenges of radar target recognition. Topics covered include the problem as applied to th

  7. Feature detection with automatic scale selection

    OpenAIRE

    Lindeberg, Tony

    1998-01-01

    The fact that objects in the world appear in different ways depending on the scale of observation has important implications if one aims at describing them. It shows that the notion of scale is of utmost importance when processing unknown measurement data by automatic methods. Whereas scale-space representation provides a well-founded framework for dealing with this issue by representing image structures at different scales, traditional scale-space theory does not address the problem of how t...

  8. Advanced automatic target recognition for police helicopter missions

    Science.gov (United States)

    Stahl, Christoph; Schoppmann, Paul

    2000-08-01

    The results of a case study about the application of an advanced method for automatic target recognition to infrared imagery taken from police helicopter missions are presented. The method consists of the following steps: preprocessing, classification, fusion, postprocessing and tracking, and combines the three paradigms image pyramids, neural networks and bayesian nets. The technology has been developed using a variety of different scenes typical for military aircraft missions. Infrared cameras have been in use for several years at the Bavarian police helicopter forces and are highly valuable for night missions. Several object classes like 'persons' or 'vehicles' are tested and the possible discrimination between persons and animals is shown. The analysis of complex scenes with hidden objects and clutter shows the potentials and limitations of automatic target recognition for real-world tasks. Several display concepts illustrate the achievable improvement of the situation awareness. The similarities and differences between various mission types concerning object variability, time constraints, consequences of false alarms, etc. are discussed. Typical police actions like searching for missing persons or runaway criminals illustrate the advantages of automatic target recognition. The results demonstrate the possible operational benefits for the helicopter crew. Future work will include performance evaluation issues and a system integration concept for the target platform.

  9. Size-based protocol optimization using automatic tube current modulation and automatic kV selection in computed tomography.

    Science.gov (United States)

    MacDougall, Robert D; Kleinman, Patricia L; Callahan, Michael J

    2016-01-01

    Size-based diagnostic reference ranges (DRRs) for contrast-enhanced pediatric abdominal computed tomography (CT) have been published in order to establish practical upper and lower limits of CTDI, DLP, and SSDE. Based on these DRRs, guidelines for establishing size-based SSDE target levels from the SSDE of a standard adult by applying a linear correction factor have been published and provide a great reference for dose optimization initiatives. The necessary step of designing manufacturer-specific CT protocols to achieve established SSDE targets is the responsibility of the Qualified Medical Physicist. The task is straightforward if fixed-mA protocols are used, however, more difficult when automatic exposure control (AEC) and automatic kV selection are considered. In such cases, the physicist must deduce the operation of AEC algorithms from technical documentation or through testing, using a wide range of phantom sizes. Our study presents the results of such testing using anthropomorphic phantoms ranging in size from the newborn to the obese adult. The effect of each user-controlled parameter was modeled for a single-manufacturer AEC algorithm (Siemens CARE Dose4D) and automatic kV selection algorithm (Siemens CARE kV). Based on the results presented in this study, a process for designing mA-modulated, pediatric abdominal CT protocols that achieve user-defined SSDE and kV targets is described. PMID:26894344

  10. Automatic radar target recognition of objects falling on railway tracks

    International Nuclear Information System (INIS)

    This paper presents an automatic radar target recognition procedure based on complex resonances using the signals provided by ultra-wideband radar. This procedure is dedicated to detection and identification of objects lying on railway tracks. For an efficient complex resonance extraction, a comparison between several pole extraction methods is illustrated. Therefore, preprocessing methods are presented aiming to remove most of the erroneous poles interfering with the discrimination scheme. Once physical poles are determined, a specific discrimination technique is introduced based on the Euclidean distances. Both simulation and experimental results are depicted showing an efficient discrimination of different targets including guided transport passengers

  11. Strategies for SETI target selection

    Science.gov (United States)

    Latham, David W.; Soderblom, David R.

    1993-08-01

    The NASA High Resolution Microwave Survey consists of two complementary elements: a Sky Survey of the entire sky to a moderate level of sensitivity; and a Targeted Search of nearby stars, one at a time, to a much deeper level of sensitivity. In this paper we present a strategy for target selection and observing. The strategy has two goals: to improve the chances of successful detection of signals from technical civilizations that inhabit planets around solar- type stars, and to minimize the chances of missing signals from unexpected sites. For the main Targeted Search survey of approximately 1000 nearby solar-type stars, we argue that the selection criteria should be heavily biased by what we know about the origin and evolution of life here on earth. We propose that observations of stars with stellar companions orbiting near the habitable zone should be de-emphasized, because such companions would prevent the formation of habitable planets. We also propose that observations of stars younger than about three billion years should be de-emphasized in favor of older stars, because our own technical civilization took longer than three billion years to evolve here on earth.

  12. Gaussian-weighted moving-window robust automatic threshold selection

    NARCIS (Netherlands)

    Wilkinson, Michael H.F.; Petkov, N; Westenberg, MA

    2003-01-01

    A multi-scale, moving-window method for local thresholding based on Robust Automatic Threshold Selection (RATS) is developed. Using a model for the noise response of the optimal edge detector in this context, the reliability of thresholds computed at different scales is determined. The threshold com

  13. Morphological self-organizing feature map neural network with applications to automatic target recognition

    Institute of Scientific and Technical Information of China (English)

    Shijun Zhang; Zhongliang Jing; Jianxun Li

    2005-01-01

    @@ The rotation invariant feature of the target is obtained using the multi-direction feature extraction property of the steerable filter. Combining the morphological operation top-hat transform with the self-organizing feature map neural network, the adaptive topological region is selected. Using the erosion operation, the topological region shrinkage is achieved. The steerable filter based morphological self-organizing feature map neural network is applied to automatic target recognition of binary standard patterns and realworld infrared sequence images. Compared with Hamming network and morphological shared-weight networks respectively, the higher recognition correct rate, robust adaptability, quick training, and better generalization of the proposed method are achieved.

  14. Deep transfer learning for automatic target classification: MWIR to LWIR

    Science.gov (United States)

    Ding, Zhengming; Nasrabadi, Nasser; Fu, Yun

    2016-05-01

    Publisher's Note: This paper, originally published on 5/12/2016, was replaced with a corrected/revised version on 5/18/2016. If you downloaded the original PDF but are unable to access the revision, please contact SPIE Digital Library Customer Service for assistance. When dealing with sparse or no labeled data in the target domain, transfer learning shows its appealing performance by borrowing the supervised knowledge from external domains. Recently deep structure learning has been exploited in transfer learning due to its attractive power in extracting effective knowledge through multi-layer strategy, so that deep transfer learning is promising to address the cross-domain mismatch. In general, cross-domain disparity can be resulted from the difference between source and target distributions or different modalities, e.g., Midwave IR (MWIR) and Longwave IR (LWIR). In this paper, we propose a Weighted Deep Transfer Learning framework for automatic target classification through a task-driven fashion. Specifically, deep features and classifier parameters are obtained simultaneously for optimal classification performance. In this way, the proposed deep structures can extract more effective features with the guidance of the classifier performance; on the other hand, the classifier performance is further improved since it is optimized on more discriminative features. Furthermore, we build a weighted scheme to couple source and target output by assigning pseudo labels to target data, therefore we can transfer knowledge from source (i.e., MWIR) to target (i.e., LWIR). Experimental results on real databases demonstrate the superiority of the proposed algorithm by comparing with others.

  15. Efficient planar camera calibration via automatic image selection

    OpenAIRE

    Byrne, Brendan P.; Mallon, John; Whelan, Paul F.

    2009-01-01

    This paper details a novel approach to automatically selecting images which improve camera calibration results. An algorithm is presented which identifies calibration images that inherently improve camera parameter estimates based on their geometric configuration or image network geometry. Analysing images in a more intuitive geometric framework allows image networks to be formed based on the relationship between their world to image homographies. Geometrically, it is equivalent to enforcing ma...

  16. Automatic target recognition performance losses in the presence of atmospheric and camera effects

    Science.gov (United States)

    Chen, Xiaohan; Schmid, Natalia A.

    2010-04-01

    The importance of networked automatic target recognition systems for surveillance applications is continuously increasing. Because of the requirement of a low cost and limited payload, these networks are traditionally equipped with lightweight, low-cost sensors such as electro-optical (EO) or infrared sensors. The quality of imagery acquired by these sensors critically depends on the environmental conditions, type and characteristics of sensors, and absence of occluding or concealing objects. In the past, a large number of efficient detection, tracking, and recognition algorithms have been designed to operate on imagery of good quality. However, detection and recognition limits under nonideal environmental and/or sensor-based distortions have not been carefully evaluated. We introduce a fully automatic target recognition system that involves a Haar-based detector to select potential regions of interest within images, performs adjustment of detected regions, segments potential targets using a region-based approach, identifies targets using Bessel K form-based encoding, and performs clutter rejection. We investigate the effects of environmental and camera conditions on target detection and recognition performance. Two databases are involved. One is a simulated database generated using a 3-D tool. The other database is formed by imaging 10 die-cast models of military vehicles from different elevation and orientation angles. The database contains imagery acquired both indoors and outdoors. The indoors data set is composed of clear and distorted images. The distortions include defocus blur, sided illumination, low contrast, shadows, and occlusions. All images in this database, however, have a uniform (blue) background. The indoors database is applied to evaluate the degradations of recognition performance due to camera and illumination effects. The database collected outdoors includes a real background and is much more complex to process. The numerical results

  17. Automatic Dissection Position Selection for Cleavage-Stage Embryo Biopsy.

    Science.gov (United States)

    Wang, Zenan; Ang, Wei Tech

    2016-03-01

    Embryo biopsies are routinely performed for preimplantation genetic diagnosis (PGD). In order to avoid blastomere membrane rupture and cell lysis, correct selection of a suitable dissection position on the zona pellucida (ZP) is necessary. Although, the technology for automated cell manipulation has advanced greatly over the past decade, fully automated embryo biopsy in PGD has not been realized yet. Automated PGD may ultimately set a new clinical standard that improves the consistency of outcomes, increases cell survival rates, flattens the learning curve of the manual procedure, and reduces the effects of human fatigue. In this paper, we present the first approach to automatically select a suitable ZP dissection position prior to embryo biopsy from a single focused embryo image based on edge detection. The proposed method consists of a technique that estimates the elliptical ZP boundaries and another two techniques that select the suitable position for ZP dissection. These techniques achieved success rates of 96%, 94%, and 94% respectively. In addition, the proposed ZP boundary estimation technique has the potential to perform ZP thickness variation (ZPTV) test and other ZP morphology measurements with further improvement in the future. Our methods provide a starting point for fast position selection prior to automatic embryo biopsy. PMID:26259216

  18. Automatic Peak Selection by a Benjamini-Hochberg-Based Algorithm

    KAUST Repository

    Abbas, Ahmed

    2013-01-07

    A common issue in bioinformatics is that computational methods often generate a large number of predictions sorted according to certain confidence scores. A key problem is then determining how many predictions must be selected to include most of the true predictions while maintaining reasonably high precision. In nuclear magnetic resonance (NMR)-based protein structure determination, for instance, computational peak picking methods are becoming more and more common, although expert-knowledge remains the method of choice to determine how many peaks among thousands of candidate peaks should be taken into consideration to capture the true peaks. Here, we propose a Benjamini-Hochberg (B-H)-based approach that automatically selects the number of peaks. We formulate the peak selection problem as a multiple testing problem. Given a candidate peak list sorted by either volumes or intensities, we first convert the peaks into p-values and then apply the B-H-based algorithm to automatically select the number of peaks. The proposed approach is tested on the state-of-the-art peak picking methods, including WaVPeak [1] and PICKY [2]. Compared with the traditional fixed number-based approach, our approach returns significantly more true peaks. For instance, by combining WaVPeak or PICKY with the proposed method, the missing peak rates are on average reduced by 20% and 26%, respectively, in a benchmark set of 32 spectra extracted from eight proteins. The consensus of the B-H-selected peaks from both WaVPeak and PICKY achieves 88% recall and 83% precision, which significantly outperforms each individual method and the consensus method without using the B-H algorithm. The proposed method can be used as a standard procedure for any peak picking method and straightforwardly applied to some other prediction selection problems in bioinformatics. The source code, documentation and example data of the proposed method is available at http://sfb.kaust.edu.sa/pages/software.aspx. © 2013

  19. Feature Extraction and Selection Strategies for Automated Target Recognition

    Science.gov (United States)

    Greene, W. Nicholas; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

    2010-01-01

    Several feature extraction and selection methods for an existing automatic target recognition (ATR) system using JPLs Grayscale Optical Correlator (GOC) and Optimal Trade-Off Maximum Average Correlation Height (OT-MACH) filter were tested using MATLAB. The ATR system is composed of three stages: a cursory region of-interest (ROI) search using the GOC and OT-MACH filter, a feature extraction and selection stage, and a final classification stage. Feature extraction and selection concerns transforming potential target data into more useful forms as well as selecting important subsets of that data which may aide in detection and classification. The strategies tested were built around two popular extraction methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). Performance was measured based on the classification accuracy and free-response receiver operating characteristic (FROC) output of a support vector machine(SVM) and a neural net (NN) classifier.

  20. Morphometric Atlas Selection for Automatic Brachial Plexus Segmentation

    International Nuclear Information System (INIS)

    Purpose: The purpose of this study was to determine the effects of atlas selection based on different morphometric parameters, on the accuracy of automatic brachial plexus (BP) segmentation for radiation therapy planning. The segmentation accuracy was measured by comparing all of the generated automatic segmentations with anatomically validated gold standard atlases developed using cadavers. Methods and Materials: Twelve cadaver computed tomography (CT) atlases (3 males, 9 females; mean age: 73 years) were included in the study. One atlas was selected to serve as a patient, and the other 11 atlases were registered separately onto this “patient” using deformable image registration. This procedure was repeated for every atlas as a patient. Next, the Dice and Jaccard similarity indices and inclusion index were calculated for every registered BP with the original gold standard BP. In parallel, differences in several morphometric parameters that may influence the BP segmentation accuracy were measured for the different atlases. Specific brachial plexus-related CT-visible bony points were used to define the morphometric parameters. Subsequently, correlations between the similarity indices and morphometric parameters were calculated. Results: A clear negative correlation between difference in protraction-retraction distance and the similarity indices was observed (mean Pearson correlation coefficient = −0.546). All of the other investigated Pearson correlation coefficients were weak. Conclusions: Differences in the shoulder protraction-retraction position between the atlas and the patient during planning CT influence the BP autosegmentation accuracy. A greater difference in the protraction-retraction distance between the atlas and the patient reduces the accuracy of the BP automatic segmentation result

  1. Morphometric Atlas Selection for Automatic Brachial Plexus Segmentation

    Energy Technology Data Exchange (ETDEWEB)

    Van de Velde, Joris, E-mail: joris.vandevelde@ugent.be [Department of Anatomy, Ghent University, Ghent (Belgium); Department of Radiotherapy, Ghent University, Ghent (Belgium); Wouters, Johan [Department of Anatomy, Ghent University, Ghent (Belgium); Vercauteren, Tom; De Gersem, Werner; Duprez, Fréderic; De Neve, Wilfried [Department of Radiotherapy, Ghent University, Ghent (Belgium); Van Hoof, Tom [Department of Anatomy, Ghent University, Ghent (Belgium)

    2015-07-01

    Purpose: The purpose of this study was to determine the effects of atlas selection based on different morphometric parameters, on the accuracy of automatic brachial plexus (BP) segmentation for radiation therapy planning. The segmentation accuracy was measured by comparing all of the generated automatic segmentations with anatomically validated gold standard atlases developed using cadavers. Methods and Materials: Twelve cadaver computed tomography (CT) atlases (3 males, 9 females; mean age: 73 years) were included in the study. One atlas was selected to serve as a patient, and the other 11 atlases were registered separately onto this “patient” using deformable image registration. This procedure was repeated for every atlas as a patient. Next, the Dice and Jaccard similarity indices and inclusion index were calculated for every registered BP with the original gold standard BP. In parallel, differences in several morphometric parameters that may influence the BP segmentation accuracy were measured for the different atlases. Specific brachial plexus-related CT-visible bony points were used to define the morphometric parameters. Subsequently, correlations between the similarity indices and morphometric parameters were calculated. Results: A clear negative correlation between difference in protraction-retraction distance and the similarity indices was observed (mean Pearson correlation coefficient = −0.546). All of the other investigated Pearson correlation coefficients were weak. Conclusions: Differences in the shoulder protraction-retraction position between the atlas and the patient during planning CT influence the BP autosegmentation accuracy. A greater difference in the protraction-retraction distance between the atlas and the patient reduces the accuracy of the BP automatic segmentation result.

  2. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    OpenAIRE

    Robertson, Scott P.; Weiss, Elisabeth; Hugo, Geoffrey D.

    2011-01-01

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy.

  3. Target selection for direct marketing.

    NARCIS (Netherlands)

    Bult, Jan Roelf

    1993-01-01

    In this thesis we concentrated on the use ol direct mail for targeting potential buyers. The major characteristics that influences the success of a plomotional direct mail campaign are the of-fbr,the communication elements, the timing or sequence of these communication elements, and the list of cus

  4. Automatic selection of tube potential for radiation dose reduction in CT: A general strategy

    International Nuclear Information System (INIS)

    Purpose: To optimize radiation dose efficiency in CT while maintaining image quality, it is important to select the optimal tube potential. The selection of optimal tube potential, however, is highly dependent on patient size and diagnostic task. The purpose of this work was to develop a general strategy that allows for automatic tube potential selection for each individual patient and each diagnostic task. Methods: The authors propose a general strategy that allows automatic adaptation of the tube potential as a function of patient size and diagnostic task, using a novel index of image quality, ''iodine contrast to noise ratio with a noise constraint (iCNRNC),'' to characterize the different image quality requirements by various clinical applications. The relative dose factor (RDF) at each tube potential to achieve a target image quality was then determined as a function of patient size and the noise constraint parameter. A workflow was developed to automatically identify the optimal tube potential that is both dose efficient and practically feasible, incorporating patient size and diagnostic task. An experimental study using a series of semianthropomorphic thoracic phantoms was used to demonstrate how the proposed general strategy can be implemented and how the radiation dose reduction achievable by the tube potential selection depends on phantom sizes and noise constraint parameters. Results: The proposed strategy provides a flexible and quantitative way to select the optimal tube potential based on the patient size and diagnostic task. The noise constraint parameter α can be adapted for different clinical applications. For example, α=1 for noncontrast routine exams; α=1.1-1.25 for contrast-enhanced routine exams; and α=1.5-2.0 for CT angiography. For the five thoracic phantoms in the experiment, when α=1, the optimal tube potentials were 80, 100, 100, 120, 120, respectively. The corresponding RDFs (relative to 120 kV) were 78.0%, 90.9%, 95.2%, 100%, and

  5. Automatic Attraction of Visual Attention by Supraletter Features of Former Target Strings

    DEFF Research Database (Denmark)

    Kyllingsbæk, Søren; Van Lommel, Sven; Sørensen, Thomas Alrik;

    2014-01-01

    Observers were trained to search for a particular horizontal string of 3 capital letters presented among similar strings consisting of exactly the same letters in different orders. The training was followed by a test in which the observers searched for a new target that was identical to one of the...... circumference of an imaginary circle around the fixation point. The training phase of Experiment 2 was similar, but in the test phase of the experiment, the strings were located in a vertical array centered on fixation, and in target-present arrays, the target always appeared at fixation. In both experiments......, performance (d’) degraded on trials in which former targets were present, suggesting that the former targets automatically drew processing resources away from the current targets. Apparently, the two experiments showed automatic attraction of visual attention by supraletter features of former target strings....

  6. Automatic target recognition of moving target based on empirical mode decomposition and genetic algorithm support vector machine

    Institute of Scientific and Technical Information of China (English)

    张军; 欧建平; 占荣辉

    2015-01-01

    In order to improve measurement accuracy of moving target signals, an automatic target recognition model of moving target signals was established based on empirical mode decomposition (EMD) and support vector machine (SVM). Automatic target recognition process on the nonlinear and non-stationary of Doppler signals of military target by using automatic target recognition model can be expressed as follows. Firstly, the nonlinearity and non-stationary of Doppler signals were decomposed into a set of intrinsic mode functions (IMFs) using EMD. After the Hilbert transform of IMF, the energy ratio of each IMF to the total IMFs can be extracted as the features of military target. Then, the SVM was trained through using the energy ratio to classify the military targets, and genetic algorithm (GA) was used to optimize SVM parameters in the solution space. The experimental results show that this algorithm can achieve the recognition accuracies of 86.15%, 87.93%, and 82.28%for tank, vehicle and soldier, respectively.

  7. Automatic Detection and Decoding of Photogrammetric Coded Targets

    OpenAIRE

    Wijenayake, Udaya; Choi, Sung-In; Park, Soon-Yong

    2016-01-01

    Close-range Photogrammetry is widely used in many industries because of the cost effectiveness and efficiency of the technique. In this research, we introduce an automated coded target detection method which can be used to enhance the efficiency of the Photogrammetry.

  8. Automatic target recognition in SAR images using multilinear analysis

    OpenAIRE

    Porgès, Tristan; Favier, Gérard

    2011-01-01

    International audience Multilinear analysis provides a powerful mathematical framework for analyzing synthetic aperture radar (SAR) images resulting from the interaction of multiple factors like sky luminosity and viewing angles, while preserving their original shape. In this paper, we propose a multilinear principal component analysis (MPCA) algorithm for target recognition in SAR images. First, we form a high order tensor with the training image set and we apply the higher-order singular...

  9. Automatic target recognition in synthetic aperture sonar images for autonomous mine hunting

    NARCIS (Netherlands)

    Quesson, B.A.J.; Sabel, J.C.; Bouma, H.; Dekker, R.J.; Lengrand-Lambert, J.

    2010-01-01

    The future of Mine Countermeasures (MCM) operations lies with unmanned platforms where Automatic Target Recognition (ATR) is an essential step in making the mine hunting process autonomous. At TNO, a new ATR method is currently being developed for use on an Autonomous Underwater Vehicle (AUV), using

  10. MaNGA: Target selection and Optimization

    Science.gov (United States)

    Wake, David

    2016-01-01

    The 6-year SDSS-IV MaNGA survey will measure spatially resolved spectroscopy for 10,000 nearby galaxies using the Sloan 2.5m telescope and the BOSS spectrographs with a new fiber arrangement consisting of 17 individually deployable IFUs. We present the simultaneous design of the target selection and IFU size distribution to optimally meet our targeting requirements. The requirements for the main samples were to use simple cuts in redshift and magnitude to produce an approximately flat number density of targets as a function of stellar mass, ranging from 1x109 to 1x1011 M⊙, and radial coverage to either 1.5 (Primary sample) or 2.5 (Secondary sample) effective radii, while maximizing S/N and spatial resolution. In addition we constructed a "Color-Enhanced" sample where we required 25% of the targets to have an approximately flat number density in the color and mass plane. We show how these requirements are met using simple absolute magnitude (and color) dependent redshift cuts applied to an extended version of the NASA Sloan Atlas (NSA), how this determines the distribution of IFU sizes and the resulting properties of the MaNGA sample.

  11. Automatic target recognition on land using three dimensional (3D laser radar and artificial neural networks

    Directory of Open Access Journals (Sweden)

    Göztepe, K.

    2013-05-01

    Full Text Available During combat, measuring the dimensions of targets is extremely important for knowing when to fire on the enemy. The importance of identifying a known target on land emphasizes the importance of techniques devoted to automatic target recognition. Although a number of object-recognition techniques have been developed in the past, none of them have provided the desired specifics for unidentified target recognition. Studies on target recognition are largely based on images that assume that images of a known target can be readily viewed under any circumstance. But this is not true for military operations conducted on various terrains under specific circumstances. Usually it is not possible to capture images of unidentified objects because of weather, inadequate equipment, or concealment. In this study, a new approach that integrates neural networks and laser radar has been developed for automatic target recognition in order to reduce the above-mentioned problems. Unlike current studies, the proposed model uses the geometric dimensions of unidentified targets in order to detect and recognise them under severe weather conditions.

  12. Evaluating PcGets and RETINA as Automatic Model Selection Algorithms.

    OpenAIRE

    Jennifer L. Castle

    2005-01-01

    The paper describes two automatic model selection algorithms, RETINA and PcGets, briefly discussing how the algorithms work and what their performance claims are. RETINA's Matlab implementation of the code is explained, then the program is compared with PcGets on the data in Perez-Amaral, Gallo and White (2005, Econometric Theory, Vol. 21, pp. 262-277), "A Comparison of Complementary Automatic Modelling Methods: RETINA and PcGets", and Hoover and Perez (1999, Econometrics Journal, Vol. 2, pp....

  13. Pseudo-Zernike Based Multi-Pass Automatic Target Recognition From Multi-Channel SAR

    OpenAIRE

    Carmine CLEMENTE; Pallotta, Luca; Proudler, Ian; De Maio, Antonio; John J. Soraghan; Farina, Alfonso

    2014-01-01

    The capability to exploit multiple sources of information is of fundamental importance in a battlefield scenario. Information obtained from different sources, and separated in space and time, provide the opportunity to exploit diversities in order to mitigate uncertainty. For the specific challenge of Automatic Target Recognition (ATR) from radar platforms, both channel (e.g. polarization) and spatial diversity can provide useful information for such a specific and critical task. In this pape...

  14. Automatic Trading Agent. RMT Based Portfolio Theory and Portfolio Selection

    Science.gov (United States)

    Snarska, M.; Krzych, J.

    2006-11-01

    Portfolio theory is a very powerful tool in the modern investment theory. It is helpful in estimating risk of an investor's portfolio, arosen from lack of information, uncertainty and incomplete knowledge of reality, which forbids a perfect prediction of future price changes. Despite of many advantages this tool is not known and not widely used among investors on Warsaw Stock Exchange. The main reason for abandoning this method is a high level of complexity and immense calculations. The aim of this paper is to introduce an automatic decision-making system, which allows a single investor to use complex methods of Modern Portfolio Theory (MPT). The key tool in MPT is an analysis of an empirical covariance matrix. This matrix, obtained from historical data, biased by such a high amount of statistical uncertainty, that it can be seen as random. By bringing into practice the ideas of Random Matrix Theory (RMT), the noise is removed or significantly reduced, so the future risk and return are better estimated and controlled. These concepts are applied to the Warsaw Stock Exchange Simulator {http://gra.onet.pl}. The result of the simulation is 18% level of gains in comparison with respective 10% loss of the Warsaw Stock Exchange main index WIG.

  15. Automatic Trading Agent. RMT based Portfolio Theory and Portfolio Selection

    CERN Document Server

    Snarska, M; Snarska, Malgorzata; Krzych, Jakub

    2006-01-01

    Portfolio theory is a very powerful tool in the modern investment theory. It is helpful in estimating risk of an investor's portfolio, which arises from our lack of information, uncertainty and incomplete knowledge of reality, which forbids a perfect prediction of future price changes. Despite of many advantages this tool is not known and is not widely used among investors on Warsaw Stock Exchange. The main reason for abandoning this method is a high level of complexity and immense calculations. The aim of this paper is to introduce an automatic decision - making system, which allows a single investor to use such complex methods of Modern Portfolio Theory (MPT). The key tool in MPT is an analysis of an empirical covariance matrix. This matrix, obtained from historical data is biased by such a high amount of statistical uncertainty, that it can be seen as random. By bringing into practice the ideas of Random Matrix Theory (RMT), the noise is removed or significantly reduced, so the future risk and return are b...

  16. Coronary CT angiography: automatic cardiac-phase selection for image reconstruction

    Energy Technology Data Exchange (ETDEWEB)

    Ruzsics, Balazs; Brothers, Robin L.; Costello, Philip [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Gebregziabher, Mulugeta [Medical University of South Carolina, Department of Biostatistics, Bioinformatics, and Epidemiology, Charleston, SC (United States); Lee, Heon [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Seoul Medical Center, Department of Radiology, Seoul (Korea); Allmendinger, Thomas; Vogt, Sebastian [Siemens Medical Solutions, Division CT, Forchheim (Germany); Schoepf, U.J. [Medical University of South Carolina, Department of Radiology and Radiological Science, Charleston, SC (United States); Medical University of South Carolina, Division of Cardiology, Charleston, SC (United States)

    2009-08-15

    We evaluated an algorithm for automatic selection of the cardiac phase with the least motion for image reconstruction at coronary computed tomography (CT) angiography (CCTA). We analyzed data of 100 patients (49 female, mean age 59 years) who had undergone retrospectively ECG-gated CCTA. Two experienced observers visually identified the most suitable end-systolic and end-diastolic phases using a series of image reconstructions in 5% increments across the RR cycle. The same data were then reconstructed using an automatic phase finding algorithm based on a 4D weighting function of cardiac motion. On average, the algorithm determined the most suitable systolic reconstruction phase at 40.11{+-}6.29% RR compared with 40.07{+-}5.58% RR by the human observers (p=NS). The most suitable diastolic phase was found at 72.71{+-}7.37% RR by the automatic algorithm, compared with 76.43{+-}6.35% RR by the observers (p<0.05). No statistically significant difference was found between automatically and visually determined reconstruction phases regarding motion and stair-step artifacts in either systole or diastole (p>0.05). Thus, there appears to be no relevant difference between an automatic phase finding algorithm and visual selection by experienced observers for determining the phase with the least cardiac motion for CCTA image reconstruction. The use of automatic phase finding may therefore facilitate the performance of cardiac CT and reduce human error. (orig.)

  17. Automatic Selection of Suitable Sentences for Language Learning Exercises

    Science.gov (United States)

    Pilán, Ildikó; Volodina, Elena; Johansson, Richard

    2013-01-01

    In our study we investigated second and foreign language (L2) sentence readability, an area little explored so far in the case of several languages, including Swedish. The outcome of our research consists of two methods for sentence selection from native language corpora based on Natural Language Processing (NLP) and machine learning (ML)…

  18. Using locality-constrained linear coding in automatic target detection of HRS images

    Science.gov (United States)

    Rezaee, M.; Mirikharaji, Z.; Zhang, Y.

    2016-04-01

    Automatic target detection with complicated shapes in high spatial resolution images is an ongoing challenge in remote sensing image processing. This is because most methods use spectral or texture information, which are not sufficient for detecting complex shapes. In this paper, a new detection framework, based on Spatial Pyramid Matching (SPM) and Locality- constraint Linear Coding (LLC), is proposed to solve this problem, and exemplified using airplane shapes. The process starts with partitioning the image into sub-regions and generating a unique histogram for local features of each sub-region. Then, linear Support Vector Machines (SVMs) are used to detect objects based on a pyramid-matching kernel, which analyses the descriptors inside patches in different resolution. In order to generate the histogram, first a point feature detector (e.g. SIFT) is applied on the patches, and then a quantization process is used to select local features. In this step, the k-mean method is used in conjunction with the locality-constrained linear coding method. The LLC forces the coefficient matrix in the quantization process to be local and sparse as well. As a result, the speed of the method improves around 24 times in comparison to using sparse coding for quantization. Quantitative analysis also shows improvement in comparison to just using k-mean, but the accuracy in comparison to using sparse coding is similar. Rotation and shift of the desired object has no effect on the obtained results. The speed and accuracy of this algorithm for high spatial resolution images make it capable for use in real-world applications.

  19. MAXIMUM A POSTERIORI-BASED AUTOMATIC TARGET DETECTION IN SAR IMAGES

    Institute of Scientific and Technical Information of China (English)

    Wang Yimin; An Jinwen

    2005-01-01

    The paper presents an algorithm of automatic target detection in Synthetic Aperture Radar(SAR) images based on Maximum A Posteriori(MAP). The algorithm is divided into three steps. First, it employs Gaussian mixture distribution to approximate and estimate multi-modal histogram of SAR image. Then, based on the principle of MAP, when a priori probability is both unknown and learned respectively, the sample pixels are classified into different classes c = {target,shadow, background}. Last, it compares the results of two different target detections. Simulation results preferably indicate that the presented algorithm is fast and robust, with the learned a priori probability, an approach to target detection is reliable and promising.

  20. Automatic Selection of the Optimal Local Feature Detector

    OpenAIRE

    Ferrarini, Bruno; Ehsan, Shoaib; Rehman, Naveed ur; Leonardis, Ales; McDonald-Maier, Klaus D.

    2016-01-01

    A large number of different feature detectors has been proposed so far. Any existing approach presents strengths and weaknesses, which make a detector optimal only for a limited range of applications. A tool capable of selecting the optimal feature detector in relation to the operating conditions is presented in this paper. The input images are quickly analyzed to determine what type of image transformation is applied to them and at which amount. Finally, the detector that is expected to obta...

  1. Study of an automatized experimental device for the irradiation of a radioactive target

    International Nuclear Information System (INIS)

    In order to solve the enigma of solar neutrinos, a team of physicians of the nuclear research center of Bordeaux-Gradignan and of the center of nuclear spectroscopy and mass spectroscopy of Orsay (France) decided to measure again the cross section of the beryllium-proton nuclear reaction at the lowest possible energies. This measurement requires the design of an automatized experimental device to irradiate in a specific way a beryllium target with an accelerated proton beam. The aim of this work is the study of such a device for an energy range of 800 to 300 KeV. This device comprises a particle multi-detector and a shutter for the irradiation of the target and the counting of the reaction products according to a programmable time sequence. The advantage of this setup is to allow an important bombardment of the target and to ensure its cooling. This device is automatically controlled thanks to a micro-controller, actuators (step motors and electrostatic deflector). It includes some beam diagnosis elements controlled by step motors and a target temperature monitoring system controlling a safety valve. The management of the experiment cell vacuum has led to the design of a vacuum monitor allowing the precise follow up of the vacuum and the control of the safety valves of the device. The nuclear instrumentation necessary to be implemented for this measurement is also presented. (J.S.)

  2. Computer-assisted microballoon selection for inertial confinement fusion targets

    International Nuclear Information System (INIS)

    Current inertial confinement fusion experiments require large numbers of well-characterized microballoon targets. Microballoons are batch-produced, and balloons of target quality are selected based on several parameters: outside diameter, wall thickness, and wall concentricity. Selection and characterization of these targets is a labor intensive process. We have developed a computer-controlled microballoon selection system that allows us to select microballoons five times faster than our previous methods with less operator fatigue and with less emphasis on operator skill

  3. Automatic selection of resting-state networks with functional magnetic resonance imaging

    Directory of Open Access Journals (Sweden)

    Silvia Francesca eStorti

    2013-05-01

    Full Text Available Functional magnetic resonance imaging (fMRI during a resting-state condition can reveal the co-activation of specific brain regions in distributed networks, called resting-state networks, which are selected by independent component analysis (ICA of the fMRI data. One of the major difficulties with component analysis is the automatic selection of the ICA features related to brain activity. In this study we describe a method designed to automatically select networks of potential functional relevance, specifically, those regions known to be involved in motor function, visual processing, executive functioning, auditory processing, memory, and the default-mode network. To do this, image analysis was based on probabilistic ICA as implemented in FSL software. After decomposition, the optimal number of components was selected by applying a novel algorithm which takes into account, for each component, Pearson's median coefficient of skewness of the spatial maps generated by FSL, followed by clustering, segmentation, and spectral analysis. To evaluate the performance of the approach, we investigated the resting-state networks in 25 subjects. For each subject, three resting-state scans were obtained with a Siemens Allegra 3 T scanner (NYU data set. Comparison of the visually and the automatically identified neuronal networks showed that the algorithm had high accuracy (first scan: 95%, second scan: 95%, third scan: 93% and precision (90%, 90%, 84%. The reproducibility of the networks for visual and automatic selection was very close: it was highly consistent in each subject for the default-mode network (≥ 92% and the occipital network, which includes the medial visual cortical areas (≥ 94%, and consistent for the attention network (≥ 80%, the right and/or left lateralized frontoparietal attention networks, and the temporal-motor network (≥ 80%. The automatic selection method may be used to detect neural networks and reduce subjectivity in ICA

  4. Blood Vessel Segmentation Using Moving-Window Robust Automatic Threshold Selection

    NARCIS (Netherlands)

    Wilkinson, Michael H.F.; Wijbenga, Tsjipke; Vries, Gijs de; Westenberg, Michel A.

    2003-01-01

    Two moving-window methods, using either flat or Gaussian weighted windows, for local thresholding with Robust Automatic Threshold Selection are developed. The results show that fast segmentation of blood vessels against a varying background and noise is possible at modest computational cost. Volumes

  5. Automatic training sample selection for a multi-evidence based crop classification approach

    DEFF Research Database (Denmark)

    Chellasamy, Menaka; Ferre, Ty; Greve, Mogens Humlekrog

    three Multi-Layer Perceptron (MLP) neural networks trained separately with spectral, texture and vegetation indices; classification labels were then assigned based on Endorsement Theory. The present study proposes an approach to feed this ensemble classifier with automatically selected training samples...

  6. Automatic geolocation of targets tracked by aerial imaging platforms using satellite imagery

    Science.gov (United States)

    Shukla, P. K.; Goel, S.; Singh, P.; Lohani, B.

    2014-11-01

    Tracking of targets from aerial platforms is an important activity in several applications, especially surveillance. Knowled ge of geolocation of these targets adds additional significant and useful information to the application. This paper determines the geolocation of a target being tracked from an aerial platform using the technique of image registration. Current approaches utilize a POS to determine the location of the aerial platform and then use the same for geolocation of the targets using the principle of photogrammetry. The constraints of cost and low-payload restrict the applicability of this approach using UAV platforms. This paper proposes a methodology for determining the geolocation of a target tracked from an aerial platform in a partially GPS devoid environment. The method utilises automatic feature based registration technique of a georeferenced satellite image with an ae rial image which is already stored in UAV's database to retrieve the geolocation of the target. Since it is easier to register subsequent aerial images due to similar viewing parameters, the subsequent overlapping images are registered together sequentially thus resulting in the registration of each of the images with georeferenced satellite image thus leading to geolocation of the target under interest. Using the proposed approach, the target can be tracked in all the frames in which it is visible. The proposed concept is verified experimentally and the results are found satisfactory. Using the proposed method, a user can obtain location of target of interest as well features on ground without requiring any POS on-board the aerial platform. The proposed approach has applications in surveillance for target tracking, target geolocation as well as in disaster management projects like search and rescue operations.

  7. Automatic detection of sea-sky horizon line and small targets in maritime infrared imagery

    Science.gov (United States)

    Kong, Xiangyu; Liu, Lei; Qian, Yunsheng; Cui, Minjie

    2016-05-01

    It is usually difficult but important to extract distant targets from sea clutters and clouds since the targets are small compared to the pixel field of view. In this paper, an algorithm based on wavelet transformation is proposed for automatic detection of small targets under the maritime background. We recognize that the distant small targets generally appear near the sea-sky horizon line and noises lie along the direction of sea-sky horizon line. So the sea-sky horizon is located firstly by examining the approximate image of a Haar wavelet decomposition of the original image. And the equation of the sea-sky horizon is set up, no matter whether the sea-sky horizon is horizontal or not. Since the sea-sky horizon is located, not only the potential area but also the strip direction of noise is got. Then the modified mutual wavelet energy combination algorithm is applied to extract targets with targets being marked by red windows. Computer simulations are shown to validate the great adaptability of the sea-sky horizon line detection and the accuracy of the small targets detection. The algorithm should be useful to engineers and scientists to design precise guidance or maritime monitoring system.

  8. Reference spectral signature selection using density-based cluster for automatic oil spill detection in hyperspectral images.

    Science.gov (United States)

    Liu, Delian; Zhang, Jianqi; Wang, Xiaorui

    2016-04-01

    Reference spectral signature selection is a fundamental work for automatic oil spill detection. To address this issue, a new approach is proposed here, which employs the density-based cluster to select a specific spectral signature from a hyperspectral image. This paper first introduces the framework of oil spill detection from hyperspectral images, indicating that detecting oil spill requires a reference spectral signature of oil spill, parameters of background, and a target detection algorithm. Based on the framework, we give the new reference spectral signature selection approach in details. Then, we demonstrate the estimation of background parameters according to the reflectance of seawater in the infrared bands. Next, the conventional adaptive cosine estimator (ACE) algorithm is employed to achieve oil spill detection. Finally, the proposed approach is tested via several practical hyperspectral images that are collected during the Horizon Deep water oil spill. The experimental results show that this new approach can automatically select the reference spectral signature of oil spills from hyperspectral images and has high detection performance. PMID:27137031

  9. Tuning target selection algorithms to improve galaxy redshift estimates

    CERN Document Server

    Hoyle, Ben; Rau, Markus Michael; Seitz, Stella; Weller, Jochen

    2015-01-01

    We showcase machine learning (ML) inspired target selection algorithms to determine which of all potential targets should be selected first for spectroscopic follow up. Efficient target selection can improve the ML redshift uncertainties as calculated on an independent sample, while requiring less targets to be observed. We compare the ML targeting algorithms with the Sloan Digital Sky Survey (SDSS) target order, and with a random targeting algorithm. The ML inspired algorithms are constructed iteratively by estimating which of the remaining target galaxies will be most difficult for the machine learning methods to accurately estimate redshifts using the previously observed data. This is performed by predicting the expected redshift error and redshift offset (or bias) of all of the remaining target galaxies. We find that the predicted values of bias and error are accurate to better than 10-30% of the true values, even with only limited training sample sizes. We construct a hypothetical follow-up survey and fi...

  10. Analgorithmic Framework for Automatic Detection and Tracking Moving Point Targets in IR Image Sequences

    Directory of Open Access Journals (Sweden)

    R. Anand Raji

    2015-05-01

    Full Text Available Imaging sensors operating in infrared (IR region of electromagnetic spectrum are gaining importance in airborne automatic target recognition (ATR applications due to their passive nature of operation. IR imaging sensors exploit the unintended IR radiation emitted by the targets of interest for detection. The ATR systems based on the passive IR imaging sensors employ a set of signal processing algorithms for processing the image information in real-time. The real-time execution of signal processing algorithms provides the sufficient reaction time to the platform carrying ATR system to react upon the target of interest. These set of algorithms include detection, tracking, and classification of low-contrast, small sized-targets. Paper explained a signal processing framework developed to detect and track moving point targets from the acquired IR image sequences in real-time.Defence Science Journal, Vol. 65, No. 3, May 2015, pp.208-213, DOI: http://dx.doi.org/10.14429/dsj.65.8164

  11. Automatic determination of the number of targets present when using the time reversal operator.

    Science.gov (United States)

    Quinlan, Angela; Barbot, Jean-Pierre; Larzabal, Pascal

    2006-04-01

    Acoustical time reversal mirrors have been shown to provide a highly accurate means of studying and focusing on acoustical sources. The DORT method is a derivation of the time reversal process, which allows for focusing on multiple targets. An important step in this process is the determination of the number of targets or sources present. This is achieved by examining the eigenvalues of the time reversal operator (TRO). The number of significant eigenvalues is then chosen as the number of sources present. However, as mentioned in [N. Mordant, C. Prada, and M. Fink, J. Acoust. Soc. Am. 105, 2634-2642 (1999) and C. Prada, M. Tanter, and M. Fink, in Proceedings of the IEEE Symposium, 1997, pp. 679-683], factors such as low signal to noise ratio (SNR), small data sample, array configuration and the target location may result in the eigenvalues corresponding to the targets no longer being distinguishable from the background noise eigenvalues. This paper proposes a robust method of automatically determining the number of targets even in the presence of a small number of snapshots. For white Gaussian noise, the profile of the ordered eigenvalues is seen to fit an exponential law. The observed eigenvalues are then compared to this model and a mismatch is detected between the observed profile and the noise-only model. The index of the mismatch gives the number of scatterers present. PMID:16642836

  12. Clinical evaluation of automatic tube voltage selection in chest CT angiography

    Energy Technology Data Exchange (ETDEWEB)

    Niemann, Tilo; Henry, Simon; Faivre, Jean-Baptiste; Yasunaga, Kanna; Bendaoud, Sofiane; Simeone, Ariana; Remy, Jacques [University Lille Nord de France, Department of Thoracic Imaging, Hospital Calmette (EA 2694), Lille (France); Duhamel, Alain [University Lille Nord de France, Department of Medical Statistics (EA 2694), Lille (France); Flohr, Thomas [Siemens Medical Systems, Department of Research and Development, Forchheim (Germany); Remy-Jardin, Martine [Hospital Calmette, Department of Thoracic Imaging, Lille cedex (France)

    2013-10-15

    To evaluate the clinical impact of automatic tube voltage selection on chest CT angiography (CTA). Ninety-three patients were prospectively evaluated with a CT protocol aimed at comparing two successive CTAs acquired under similar technical conditions except for the kV selection: (1) the initial CTA was systematically obtained at 120 kVp and 90 ref mAs; (2) the follow-up CTA was obtained with an automatic selection of the kilovoltage (Care KV; Siemens Healthcare) for optimised CTA. At follow-up, 90 patients (97 %) underwent CTA with reduced tube voltage, 100 kV (n = 26; 28 %) and 80 kV (n = 64; 69 %), resulting in a significant dose-length-product reduction (follow-up: 87.27; initial: 141.88 mGy.cm; P < 0.0001; mean dose reduction: 38.5 %) and a significant increase in the CNR at follow-up (follow-up: 11.5 {+-} 3.5 HU; initial: 10.9 {+-} 3.7 HU; P = 0.03). The increase in objective image noise at follow-up (follow-up: 23.2 {+-} 6.7 HU vs. 17.8 {+-} 5.1 HU; P < 0.0001) did not alter the diagnostic value of images. Automatic tube voltage selection reduced the radiation dose delivered during chest CT angiograms by 38.5 % while improving the contrast-to-noise ratio of the examinations. (orig.)

  13. Atlas-based automatic segmentation of head and neck organs at risk and nodal target volumes: a clinical validation

    OpenAIRE

    Daisne, Jean-François; Blumhofer, Andreas

    2013-01-01

    Background Intensity modulated radiotherapy for head and neck cancer necessitates accurate definition of organs at risk (OAR) and clinical target volumes (CTV). This crucial step is time consuming and prone to inter- and intra-observer variations. Automatic segmentation by atlas deformable registration may help to reduce time and variations. We aim to test a new commercial atlas algorithm for automatic segmentation of OAR and CTV in both ideal and clinical conditions. Methods The updated Brai...

  14. Selectively targeting estrogen receptors for cancer treatment

    NARCIS (Netherlands)

    Shanle, Erin K.; Xu, Wei

    2010-01-01

    Estrogens regulate growth and development through the action of two distinct estrogen receptors (ERs), ER alpha and ER beta, which mediate proliferation and differentiation of cells. For decades, ER alpha mediated estrogen signaling has been therapeutically targeted to treat breast cancer, most nota

  15. Robust Ground Target Detection by SAR and IR Sensor Fusion Using Adaboost-Based Feature Selection.

    Science.gov (United States)

    Kim, Sungho; Song, Woo-Jin; Kim, So-Hyun

    2016-01-01

    Long-range ground targets are difficult to detect in a noisy cluttered environment using either synthetic aperture radar (SAR) images or infrared (IR) images. SAR-based detectors can provide a high detection rate with a high false alarm rate to background scatter noise. IR-based approaches can detect hot targets but are affected strongly by the weather conditions. This paper proposes a novel target detection method by decision-level SAR and IR fusion using an Adaboost-based machine learning scheme to achieve a high detection rate and low false alarm rate. The proposed method consists of individual detection, registration, and fusion architecture. This paper presents a single framework of a SAR and IR target detection method using modified Boolean map visual theory (modBMVT) and feature-selection based fusion. Previous methods applied different algorithms to detect SAR and IR targets because of the different physical image characteristics. One method that is optimized for IR target detection produces unsuccessful results in SAR target detection. This study examined the image characteristics and proposed a unified SAR and IR target detection method by inserting a median local average filter (MLAF, pre-filter) and an asymmetric morphological closing filter (AMCF, post-filter) into the BMVT. The original BMVT was optimized to detect small infrared targets. The proposed modBMVT can remove the thermal and scatter noise by the MLAF and detect extended targets by attaching the AMCF after the BMVT. Heterogeneous SAR and IR images were registered automatically using the proposed RANdom SAmple Region Consensus (RANSARC)-based homography optimization after a brute-force correspondence search using the detected target centers and regions. The final targets were detected by feature-selection based sensor fusion using Adaboost. The proposed method showed good SAR and IR target detection performance through feature selection-based decision fusion on a synthetic database generated

  16. Robust Ground Target Detection by SAR and IR Sensor Fusion Using Adaboost-Based Feature Selection

    Directory of Open Access Journals (Sweden)

    Sungho Kim

    2016-07-01

    Full Text Available Long-range ground targets are difficult to detect in a noisy cluttered environment using either synthetic aperture radar (SAR images or infrared (IR images. SAR-based detectors can provide a high detection rate with a high false alarm rate to background scatter noise. IR-based approaches can detect hot targets but are affected strongly by the weather conditions. This paper proposes a novel target detection method by decision-level SAR and IR fusion using an Adaboost-based machine learning scheme to achieve a high detection rate and low false alarm rate. The proposed method consists of individual detection, registration, and fusion architecture. This paper presents a single framework of a SAR and IR target detection method using modified Boolean map visual theory (modBMVT and feature-selection based fusion. Previous methods applied different algorithms to detect SAR and IR targets because of the different physical image characteristics. One method that is optimized for IR target detection produces unsuccessful results in SAR target detection. This study examined the image characteristics and proposed a unified SAR and IR target detection method by inserting a median local average filter (MLAF, pre-filter and an asymmetric morphological closing filter (AMCF, post-filter into the BMVT. The original BMVT was optimized to detect small infrared targets. The proposed modBMVT can remove the thermal and scatter noise by the MLAF and detect extended targets by attaching the AMCF after the BMVT. Heterogeneous SAR and IR images were registered automatically using the proposed RANdom SAmple Region Consensus (RANSARC-based homography optimization after a brute-force correspondence search using the detected target centers and regions. The final targets were detected by feature-selection based sensor fusion using Adaboost. The proposed method showed good SAR and IR target detection performance through feature selection-based decision fusion on a synthetic

  17. Tuning target selection algorithms to improve galaxy redshift estimates

    Science.gov (United States)

    Hoyle, Ben; Paech, Kerstin; Rau, Markus Michael; Seitz, Stella; Weller, Jochen

    2016-06-01

    We showcase machine learning (ML) inspired target selection algorithms to determine which of all potential targets should be selected first for spectroscopic follow-up. Efficient target selection can improve the ML redshift uncertainties as calculated on an independent sample, while requiring less targets to be observed. We compare seven different ML targeting algorithms with the Sloan Digital Sky Survey (SDSS) target order, and with a random targeting algorithm. The ML inspired algorithms are constructed iteratively by estimating which of the remaining target galaxies will be most difficult for the ML methods to accurately estimate redshifts using the previously observed data. This is performed by predicting the expected redshift error and redshift offset (or bias) of all of the remaining target galaxies. We find that the predicted values of bias and error are accurate to better than 10-30 per cent of the true values, even with only limited training sample sizes. We construct a hypothetical follow-up survey and find that some of the ML targeting algorithms are able to obtain the same redshift predictive power with 2-3 times less observing time, as compared to that of the SDSS, or random, target selection algorithms. The reduction in the required follow-up resources could allow for a change to the follow-up strategy, for example by obtaining deeper spectroscopy, which could improve ML redshift estimates for deeper test data.

  18. Dynamic Data Driven Applications Systems (DDDAS) modeling for automatic target recognition

    Science.gov (United States)

    Blasch, Erik; Seetharaman, Guna; Darema, Frederica

    2013-05-01

    The Dynamic Data Driven Applications System (DDDAS) concept uses applications modeling, mathematical algorithms, and measurement systems to work with dynamic systems. A dynamic systems such as Automatic Target Recognition (ATR) is subject to sensor, target, and the environment variations over space and time. We use the DDDAS concept to develop an ATR methodology for multiscale-multimodal analysis that seeks to integrated sensing, processing, and exploitation. In the analysis, we use computer vision techniques to explore the capabilities and analogies that DDDAS has with information fusion. The key attribute of coordination is the use of sensor management as a data driven techniques to improve performance. In addition, DDDAS supports the need for modeling from which uncertainty and variations are used within the dynamic models for advanced performance. As an example, we use a Wide-Area Motion Imagery (WAMI) application to draw parallels and contrasts between ATR and DDDAS systems that warrants an integrated perspective. This elementary work is aimed at triggering a sequence of deeper insightful research towards exploiting sparsely sampled piecewise dense WAMI measurements - an application where the challenges of big-data with regards to mathematical fusion relationships and high-performance computations remain significant and will persist. Dynamic data-driven adaptive computations are required to effectively handle the challenges with exponentially increasing data volume for advanced information fusion systems solutions such as simultaneous target tracking and ATR.

  19. Selecting asteroids for a targeted spectroscopic survey

    CERN Document Server

    Oszkiewicz, D A; Tomov, T; Birlan, M; Geier, S; Penttilä, A; Polińska, M

    2014-01-01

    Asteroid spectroscopy reflects surface mineralogy. There are few thousand asteroids whose surfaces have been observed spectrally. Determining the surface properties of those objects is important for many practical and scientific applications, such as for example developing impact deflection strategies or studying history and evolution of the Solar System and planet formation. The aim of this study is to develop a pre-selection method that can be utilized in searching for asteroids of any taxonomic complex. The method could then be utilized im multiple applications such as searching for the missing V-types or looking for primitive asteroids. We used the Bayes Naive Classifier combined with observations obtained in the course of the Sloan Digital Sky Survey and the Wide-field Infrared Survey Explorer surveys as well as a database of asteroid phase curves for asteroids with known taxonomic type. Using the new classification method we have selected a number of possible V-type candidates. Some of the candidates we...

  20. Sexual selection targets cetacean pelvic bones.

    Science.gov (United States)

    Dines, James P; Otárola-Castillo, Erik; Ralph, Peter; Alas, Jesse; Daley, Timothy; Smith, Andrew D; Dean, Matthew D

    2014-11-01

    Male genitalia evolve rapidly, probably as a result of sexual selection. Whether this pattern extends to the internal infrastructure that influences genital movements remains unknown. Cetaceans (whales and dolphins) offer a unique opportunity to test this hypothesis: since evolving from land-dwelling ancestors, they lost external hind limbs and evolved a highly reduced pelvis that seems to serve no other function except to anchor muscles that maneuver the penis. Here, we create a novel morphometric pipeline to analyze the size and shape evolution of pelvic bones from 130 individuals (29 species) in the context of inferred mating system. We present two main findings: (1) males from species with relatively intense sexual selection (inferred by relative testes size) tend to evolve larger penises and pelvic bones compared to their body length, and (2) pelvic bone shape has diverged more in species pairs that have diverged in inferred mating system. Neither pattern was observed in the anterior-most pair of vertebral ribs, which served as a negative control. This study provides evidence that sexual selection can affect internal anatomy that controls male genitalia. These important functions may explain why cetacean pelvic bones have not been lost through evolutionary time. PMID:25186496

  1. Localization accuracy from automatic and semi-automatic rigid registration of locally-advanced lung cancer targets during image-guided radiation therapy

    International Nuclear Information System (INIS)

    Purpose: To evaluate localization accuracy resulting from rigid registration of locally-advanced lung cancer targets using fully automatic and semi-automatic protocols for image-guided radiation therapy. Methods: Seventeen lung cancer patients, fourteen also presenting with involved lymph nodes, received computed tomography (CT) scans once per week throughout treatment under active breathing control. A physician contoured both lung and lymph node targets for all weekly scans. Various automatic and semi-automatic rigid registration techniques were then performed for both individual and simultaneous alignments of the primary gross tumor volume (GTVP) and involved lymph nodes (GTVLN) to simulate the localization process in image-guided radiation therapy. Techniques included ''standard'' (direct registration of weekly images to a planning CT), ''seeded'' (manual prealignment of targets to guide standard registration), ''transitive-based'' (alignment of pretreatment and planning CTs through one or more intermediate images), and ''rereferenced'' (designation of a new reference image for registration). Localization error (LE) was assessed as the residual centroid and border distances between targets from planning and weekly CTs after registration. Results: Initial bony alignment resulted in centroid LE of 7.3 ± 5.4 mm and 5.4 ± 3.4 mm for the GTVP and GTVLN, respectively. Compared to bony alignment, transitive-based and seeded registrations significantly reduced GTVP centroid LE to 4.7 ± 3.7 mm (p = 0.011) and 4.3 ± 2.5 mm (p -3), respectively, but the smallest GTVP LE of 2.4 ± 2.1 mm was provided by rereferenced registration (p -6). Standard registration significantly reduced GTVLN centroid LE to 3.2 ± 2.5 mm (p -3) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low as 3.9 ± 2.7 mm and 3.8 ± 2.3 mm were achieved for the GTVP and GTVLN, respectively, using

  2. Automatic target classification of man-made objects in synthetic aperture radar images using Gabor wavelet and neural network

    Science.gov (United States)

    Vasuki, Perumal; Roomi, S. Mohamed Mansoor

    2013-01-01

    Processing of synthetic aperture radar (SAR) images has led to the development of automatic target classification approaches. These approaches help to classify individual and mass military ground vehicles. This work aims to develop an automatic target classification technique to classify military targets like truck/tank/armored car/cannon/bulldozer. The proposed method consists of three stages via preprocessing, feature extraction, and neural network (NN). The first stage removes speckle noise in a SAR image by the identified frost filter and enhances the image by histogram equalization. The second stage uses a Gabor wavelet to extract the image features. The third stage classifies the target by an NN classifier using image features. The proposed work performs better than its counterparts, like K-nearest neighbor (KNN). The proposed work performs better on databases like moving and stationary target acquisition and recognition against the earlier methods by KNN.

  3. Improved decoding of attentional selection in a cocktail party environment with EEG via automatic selection of relevant independent components.

    Science.gov (United States)

    O'Sullivan, James A; Reilly, Richard B; Lalor, Edmund C

    2015-08-01

    Recently it has been shown to be possible to ascertain which speaker a subject is attending to in a cocktail party environment from single-trial (~60s) electroencephalography (EEG) data. The attentional selection of most of subjects could be decoded with a very high accuracy (>90%). However, the performance of many subjects fell below what would be required for a potential brain computer interface (BCI). One potential reason for this is that activity related to the stimuli may have a lower signal-to-noise ratio on the scalp for some subjects than others. Independent component analysis (ICA) is a commonly used method for denoising EEG data. However, its effective use often requires the subjective choice of the experimenter to determine which independent components (ICs) to retain and which to reject. Algorithms do exist to automatically determine the reliability of ICs, however they provide no information as to their relevance for the task at hand. Here we introduce a novel method for automatically selecting ICs which are relevant for decoding attentional selection. In doing so, we show a significant increase in classification accuracy at all test data durations from 60s to 10s. These findings have implications for the future development of naturalistic and user-friendly BCIs, as well as for smart hearing aids. PMID:26737596

  4. Computational design of nanoparticle drug delivery systems for selective targeting

    Science.gov (United States)

    Duncan, Gregg A.; Bevan, Michael A.

    2015-09-01

    Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting diseased cells and tissues.Ligand-functionalized nanoparticles capable of selectively binding to diseased versus healthy cell populations are attractive for improved efficacy of nanoparticle-based drug and gene therapies. However, nanoparticles functionalized with high affinity targeting ligands may lead to undesired off-target binding to healthy cells. In this work, Monte Carlo simulations were used to quantitatively determine net surface interactions, binding valency, and selectivity between targeted nanoparticles and cell surfaces. Dissociation constant, KD, and target membrane protein density, ρR, are explored over a range representative of healthy and cancerous cell surfaces. Our findings show highly selective binding to diseased cell surfaces can be achieved with multiple, weaker affinity targeting ligands that can be further optimized by varying the targeting ligand density, ρL. Using the approach developed in this work, nanomedicines can be optimally designed for exclusively targeting

  5. A comparative study of automatic image segmentation algorithms for target tracking in MR-IGRT.

    Science.gov (United States)

    Feng, Yuan; Kawrakow, Iwan; Olsen, Jeff; Parikh, Parag J; Noel, Camille; Wooten, Omar; Du, Dongsu; Mutic, Sasa; Hu, Yanle

    2016-01-01

    On-board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real-time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image-guided radiotherapy (MR-IGRT) system. Manual con-tours of the kidney, bladder, duodenum, and a liver tumor by an experienced radia-tion oncologist were used as the ground truth for performance evaluation. Besides the manual segmentation, images were automatically segmented using thresholding, fuzzy k-means (FKM), k-harmonic means (KHM), and reaction-diffusion level set evolution (RD-LSE) algorithms, as well as the tissue tracking algorithm provided by the ViewRay treatment planning and delivery system (VR-TPDS). The performance of the five algorithms was evaluated quantitatively by comparing with the manual segmentation using the Dice coefficient and target registration error (TRE) measured as the distance between the centroid of the manual ROI and the centroid of the automatically segmented ROI. All methods were able to successfully segment the bladder and the kidney, but only FKM, KHM, and VR-TPDS were able to segment the liver tumor and the duodenum. The performance of the thresholding, FKM, KHM, and RD-LSE algorithms degraded as the local image contrast decreased, whereas the performance of the VP-TPDS method was nearly independent of local image contrast due to the reference registration algorithm. For segmenting high-contrast images (i.e., kidney), the thresholding method provided the best speed (< 1 ms) with a satisfying accuracy (Dice = 0.95). When the image contrast was low, the VR-TPDS method had the best automatic contour. Results suggest an image quality determination procedure before segmentation and a combination of

  6. Automatic irradiation control by an optical feedback technique for selective retina treatment (SRT) in a rabbit model

    Science.gov (United States)

    Seifert, Eric; Roh, Young-Jung; Fritz, Andreas; Park, Young Gun; Kang, Seungbum; Theisen-Kunde, Dirk; Brinkmann, Ralf

    2013-06-01

    Selective Retina Therapy (SRT) targets the Retinal Pigment Epithelium (RPE) without effecting neighboring layers as the photoreceptors or the choroid. SRT related RPE defects are ophthalmoscopically invisible. Owing to this invisibility and the variation of the threshold radiant exposure for RPE damage the treating physician does not know whether the treatment was successful or not. Thus measurement techniques enabling a correct dosing are a demanded element in SRT devices. The acquired signal can be used for monitoring or automatic irradiation control. Existing monitoring techniques are based on the detection of micro-bubbles. These bubbles are the origin of RPE cell damage for pulse durations in the ns and μs time regime 5μs. The detection can be performed by optical or acoustical approaches. Monitoring based on an acoustical approach has already been used to study the beneficial effects of SRT on diabetic macula edema and central serous retinopathy. We have developed a first real time feedback technique able to detect micro-bubble induced characteristics in the backscattered laser light fast enough to cease the laser irradiation within a burst. Therefore the laser energy within a burst of at most 30 pulses is increased linearly with every pulse. The laser irradiation is ceased as soon as micro-bubbles are detected. With this automatic approach it was possible to observe invisible lesions, an intact photoreceptor layer and a reconstruction of the RPE within one week.

  7. An algorithm for preferential selection of spectroscopic targets in LEGUE

    International Nuclear Information System (INIS)

    We describe a general target selection algorithm that is applicable to any survey in which the number of available candidates is much larger than the number of objects to be observed. This routine aims to achieve a balance between a smoothly-varying, well-understood selection function and the desire to preferentially select certain types of targets. Some target-selection examples are shown that illustrate different possibilities of emphasis functions. Although it is generally applicable, the algorithm was developed specifically for the LAMOST Experiment for Galactic Understanding and Exploration (LEGUE) survey that will be carried out using the Chinese Guo Shou Jing Telescope. In particular, this algorithm was designed for the portion of LEGUE targeting the Galactic halo, in which we attempt to balance a variety of science goals that require stars at fainter magnitudes than can be completely sampled by LAMOST. This algorithm has been implemented for the halo portion of the LAMOST pilot survey, which began in October 2011.

  8. Target Tracking Feature Selection Algorithm Based on Adaboost

    OpenAIRE

    Chen Yi

    2013-01-01

         With the development of image processing technology and popularization of computer technology, intelligent machine vision technology has a wide range of application in the medical, military, industrial and other fields. Target tracking feature selection algorithm is one of research focuses in the machine intelligent vision technology. Therefore, to design the target tracking feature selection algorithm with high accuracy and good stability is extremely necessary. This paper presents a ta...

  9. Target selection biases from recent experience transfer across effectors.

    Science.gov (United States)

    Moher, Jeff; Song, Joo-Hyun

    2016-02-01

    Target selection is often biased by an observer's recent experiences. However, not much is known about whether these selection biases influence behavior across different effectors. For example, does looking at a red object make it easier to subsequently reach towards another red object? In the current study, we asked observers to find the uniquely colored target object on each trial. Randomly intermixed pre-trial cues indicated the mode of action: either an eye movement or a visually guided reach movement to the target. In Experiment 1, we found that priming of popout, reflected in faster responses following repetition of the target color on consecutive trials, occurred regardless of whether the effector was repeated from the previous trial or not. In Experiment 2, we examined whether an inhibitory selection bias away from a feature could transfer across effectors. While priming of popout reflects both enhancement of the repeated target features and suppression of the repeated distractor features, the distractor previewing effect isolates a purely inhibitory component of target selection in which a previewed color is presented in a homogenous display and subsequently inhibited. Much like priming of popout, intertrial suppression biases in the distractor previewing effect transferred across effectors. Together, these results suggest that biases for target selection driven by recent trial history transfer across effectors. This indicates that representations in memory that bias attention towards or away from specific features are largely independent from their associated actions. PMID:26563393

  10. Automatic Selection of Initial Points for Exploratory Vessel Tracing in Fluoroscopic Images

    Directory of Open Access Journals (Sweden)

    Farsad Zamani Boroujeni

    2011-09-01

    Full Text Available Automatic extraction of vessel centerlines has been an essential process in most of the image guided diagnosis and therapy applications. Among a considerable number of methods, direct exploratory tracing method is known to be an efficient solution for reliable extraction of vessel features from two-dimensional fluoroscopic images. The first step of most automatic exploratory tracing algorithms is collecting a number of candidate initial seed points and their initial tracing directions. To detect reliable initial points, a validation step is required to filter out the false candidates and avoid unnecessary tracing. Staring from reliable initial points, the algorithm efficiently extracts the centerline points along the initial direction until certain pre-defined criteria are satisfied. However, most of these algorithms suffer from incomplete results due to inappropriate selection of the initial seed points. The conventional seed point selection algorithms either rely merely on signal-to-noise ratio analysis, which results in a large number of false traces, or impose a set of strict geometrical validation rules that lead to more false negatives and require more computation time. This paper presents a new method for efficient selection of initial points for exploratory tracing algorithms. The proposed method improves the performance upon existing methods by employing a combination of geometrical and intensity-based approaches.Defence Science Journal, 2011, 61(5, pp.443-451, DOI:http://dx.doi.org/10.14429/dsj.61.1179

  11. Selection of Entropy Based Features for Automatic Analysis of Essential Tremor

    Directory of Open Access Journals (Sweden)

    Karmele López-de-Ipiña

    2016-05-01

    Full Text Available Biomedical systems produce biosignals that arise from interaction mechanisms. In a general form, those mechanisms occur across multiple scales, both spatial and temporal, and contain linear and non-linear information. In this framework, entropy measures are good candidates in order provide useful evidence about disorder in the system, lack of information in time-series and/or irregularity of the signals. The most common movement disorder is essential tremor (ET, which occurs 20 times more than Parkinson’s disease. Interestingly, about 50%–70% of the cases of ET have a genetic origin. One of the most used standard tests for clinical diagnosis of ET is Archimedes’ spiral drawing. This work focuses on the selection of non-linear biomarkers from such drawings and handwriting, and it is part of a wider cross study on the diagnosis of essential tremor, where our piece of research presents the selection of entropy features for early ET diagnosis. Classic entropy features are compared with features based on permutation entropy. Automatic analysis system settled on several Machine Learning paradigms is performed, while automatic features selection is implemented by means of ANOVA (analysis of variance test. The obtained results for early detection are promising and appear applicable to real environments.

  12. SUNMAP: A Tool for Automatic Topology Selection and Generation for NoCs

    OpenAIRE

    Murali, Srinivasan; Micheli, Giovanni De

    2004-01-01

    Increasing communication demands of processor and memory cores in Systems on Chips (SoCs) necessitate the use of Networks on Chip (NoC) to interconnect the cores. An important phase in the design of NoCs is the mapping of cores onto the most suitable topology for a given application. In this paper, we present SUNMAP a tool for automatically selecting the best topology for a given application and producing a mapping of cores onto that topology. SUNMAP explores various design objective such as ...

  13. The effect of morphometric atlas selection on multi-atlas-based automatic brachial plexus segmentation

    International Nuclear Information System (INIS)

    The present study aimed to measure the effect of a morphometric atlas selection strategy on the accuracy of multi-atlas-based BP autosegmentation using the commercially available software package ADMIRE® and to determine the optimal number of selected atlases to use. Autosegmentation accuracy was measured by comparing all generated automatic BP segmentations with anatomically validated gold standard segmentations that were developed using cadavers. Twelve cadaver computed tomography (CT) atlases were included in the study. One atlas was selected as a patient in ADMIRE®, and multi-atlas-based BP autosegmentation was first performed with a group of morphometrically preselected atlases. In this group, the atlases were selected on the basis of similarity in the shoulder protraction position with the patient. The number of selected atlases used started at two and increased up to eight. Subsequently, a group of randomly chosen, non-selected atlases were taken. In this second group, every possible combination of 2 to 8 random atlases was used for multi-atlas-based BP autosegmentation. For both groups, the average Dice similarity coefficient (DSC), Jaccard index (JI) and Inclusion index (INI) were calculated, measuring the similarity of the generated automatic BP segmentations and the gold standard segmentation. Similarity indices of both groups were compared using an independent sample t-test, and the optimal number of selected atlases was investigated using an equivalence trial. For each number of atlases, average similarity indices of the morphometrically selected atlas group were significantly higher than the random group (p < 0,05). In this study, the highest similarity indices were achieved using multi-atlas autosegmentation with 6 selected atlases (average DSC = 0,598; average JI = 0,434; average INI = 0,733). Morphometric atlas selection on the basis of the protraction position of the patient significantly improves multi-atlas-based BP autosegmentation accuracy

  14. Perceptual task induces saccadic adaptation by target selection

    Directory of Open Access Journals (Sweden)

    Alexander Christian Schütz

    2015-10-01

    We replicated our finding that a perceptual task can drive adaptation of saccades. Adaptation showed no effect of feedback reliability, nor an effect of the perceptual task beyond target selection. Adaptation was induced by a top-down signal since it was absent when there was no target selection instruction and no perceptual task. The immediate error correction was larger for the difficult than for the easy condition, suggesting that task difficulty affects mainly voluntary saccade targeting. In addition, the repetition of experiments one week later increased the magnitude of the gradual error correction. The results dissociate two distinct components of adaptation: an immediate and a gradual error correction. We conclude that perceptual-task induced adaptation is most likely due to top-down target selection within a larger object.

  15. Automatic identification of bird targets with radar via patterns produced by wing flapping.

    Science.gov (United States)

    Zaugg, Serge; Saporta, Gilbert; van Loon, Emiel; Schmaljohann, Heiko; Liechti, Felix

    2008-09-01

    Bird identification with radar is important for bird migration research, environmental impact assessments (e.g. wind farms), aircraft security and radar meteorology. In a study on bird migration, radar signals from birds, insects and ground clutter were recorded. Signals from birds show a typical pattern due to wing flapping. The data were labelled by experts into the four classes BIRD, INSECT, CLUTTER and UFO (unidentifiable signals). We present a classification algorithm aimed at automatic recognition of bird targets. Variables related to signal intensity and wing flapping pattern were extracted (via continuous wavelet transform). We used support vector classifiers to build predictive models. We estimated classification performance via cross validation on four datasets. When data from the same dataset were used for training and testing the classifier, the classification performance was extremely to moderately high. When data from one dataset were used for training and the three remaining datasets were used as test sets, the performance was lower but still extremely to moderately high. This shows that the method generalizes well across different locations or times. Our method provides a substantial gain of time when birds must be identified in large collections of radar signals and it represents the first substantial step in developing a real time bird identification radar system. We provide some guidelines and ideas for future research. PMID:18331979

  16. Resource Optimization in Automatic web page classification using integrated feature selection and machine learning

    Directory of Open Access Journals (Sweden)

    Rajaram Ramasamy

    2009-01-01

    Full Text Available Increasing with the number of users, the need for automatic classification techniques with good classification accuracy increases as search engines depend on previously classified web pages stored in classified directories to retrieve the relevant results. Preprocessing is the important step in web page classification problem as most of the web pages contain more irrelevant information than relevant details useful for finding its category. For the classification purpose the representative words in the web page called as features are used for classification rather than the entire web page to reduce time and space requirements. The selection of relevant features which reduces the high dimensionality and redundancy is the current research topic. In this paper selecting relevant features from the pages is treated as an optimization problem and we propose an algorithm to find the optimal features for web page classification. Machine learning techniques for automatic classification gains more interest as the classifier improves its performance with experience. In this paper we use Naïve Bayes, Kstar, Random Forest and Bagging machine learning classifiers.

  17. Automatic selection of informative sentences: The sentences that can generate multiple choice questions

    Directory of Open Access Journals (Sweden)

    Mukta Majumder

    2014-12-01

    Full Text Available Traditional education cannot meet the expectation and requirement of a Smart City; it require more advance forms like active learning, ICT education etc. Multiple choice questions (MCQs play an important role in educational assessment and active learning which has a key role in Smart City education. MCQs are effective to assess the understanding of well-defined concepts. A fraction of all the sentences of a text contain well-defined concepts or information that can be asked as a MCQ. These informative sentences are required to be identified first for preparing multiple choice questions manually or automatically. In this paper we propose a technique for automatic identification of such informative sentences that can act as the basis of MCQ. The technique is based on parse structure similarity. A reference set of parse structures is compiled with the help of existing MCQs. The parse structure of a new sentence is compared with the reference structures and if similarity is found then the sentence is considered as a potential candidate. Next a rule-based post-processing module works on these potential candidates to select the final set of informative sentences. The proposed approach is tested in sports domain, where many MCQs are easily available for preparing the reference set of structures. The quality of the system selected sentences is evaluated manually. The experimental result shows that the proposed technique is quite promising.

  18. Improved clutter rejection in automatic target recognition and tracking using eigen-extended maximum average correlation height (EEMACH) filter and polynomial distance classifier correlation filter (PDCCF)

    Science.gov (United States)

    Islam, M. F.; Alam, M. S.

    2006-04-01

    Various correlation based techniques for detection and classification of targets in forward looking infrared (FLIR) imagery have been developed in last two decades. Correlation filters are attractive for automatic target recognition (ATR) because of their distortion tolerance and shift invariance capabilities. The extended maximum average correlation height (EMACH) filter was developed to detect a target with low false alarm rate while providing good distortion tolerance using a trade off parameter (beta). By decomposing the EMACH filter using the eigen-analysis, another generalized filter, called the eigen-EMACH (EEMACH) filter was developed. The EEMACH filter exhibits consistent performance over a wide range which controls the trade-off between distortion tolerance and clutter rejection. In this paper, a new technique is proposed to combine the EEMACH and polynomial distance classifier correlation filter (PDCCF) for detecting and tracking both single and multiple targets in real life FLIR sequences. At first, EEMACH filter was used to select regions of interest (ROI) from input images and then PDCCF is applied to identify targets using thresholds and distance measures. Both the EEMACH and PDCCF filters are trained with different sizes and orientations corresponding to the target to be detected. This method provides improved clutter rejection capability by exploiting the eigen vectors of the desired class. Both single and multiple targets were identified in each frame by independently using EEMACH-PDCCF algorithm to avoid target disappearance problems under complicated scenarios.

  19. A load-balance path selection algorithm in automatically swiched optical network (ASON)

    Science.gov (United States)

    Gao, Fei; Lu, Yueming; Ji, Yuefeng

    2007-11-01

    In this paper, a novel load-balance algorithm is proposed to provide an approach to optimized path selection in automatically swiched optical network (ASON). By using this algorithm, improved survivability and low congestion can be achieved. The static nature of current routing algorithms, such as OSPF or IS-IS, has made the situation worse since the traffic is concentrated on the "least-cost" paths which causes the congestion for some links while leaving other links lightly loaded. So, the key is to select suitable paths to balance the network load to optimize network resource utilization and traffic performance. We present a method to provide the capability to control traffic engineering so that the carriers can define their own strategies for optimizations and apply them to path selection for dynamic load balancing. With considering load distribution and topology information, capacity utilization factor is introduced into Dijkstra (shortest path selection) for path selection to achieve balancing traffic over network. Routing simulations have been done over mesh networks to compare the two different algorithms. With the simulation results, a conclusion can be made on the performance of different algorithms.

  20. Automatic gas-levitation system for vacuum deposition of laser-fusion targets

    International Nuclear Information System (INIS)

    An improved simple system has been developed to gas-levitate microspheres during vacuum-deposition processes. The automatic operation relies on two effects: a lateral stabilizing force provided by a centering-ring; and an automatically incremented gas metering system to offset weight increases during coating

  1. Protecting Ligands Enhance Selective Targeting of Multivalent Nanoparticles

    CERN Document Server

    Angioletti-Uberti, Stefano

    2016-01-01

    Nanoparticles functionalized with multiple ligands can be programmed to bind biological targets, e.g. cells, depending on the receptors they express, providing a general platform for the development of different technologies, from selective drug-delivery to biosensing. In order to be highly selective ligands should exclusively bind to specific targeted receptors, since formation of bonds with other, untargeted ones would lead to non-specific binding and potentially harmful behaviour. This poses a particular problem for multivalent nanoparticles, because even very weak bonds can collectively lead to strong binding. A statistical mechanical model is presented here to describe the extent to which bond strength and nanoparticle valency can induce non-selective adsorption. The same model is used to describe a possible solution: functionalization of the nanoparticles with "protective" receptors. The latter compete with cell receptors for the targeting ligands, and can be optimized to strongly reduce the effect of u...

  2. ModelMage: a tool for automatic model generation, selection and management.

    Science.gov (United States)

    Flöttmann, Max; Schaber, Jörg; Hoops, Stephan; Klipp, Edda; Mendes, Pedro

    2008-01-01

    Mathematical modeling of biological systems usually involves implementing, simulating, and discriminating several candidate models that represent alternative hypotheses. Generating and managing these candidate models is a tedious and difficult task and can easily lead to errors. ModelMage is a tool that facilitates management of candidate models. It is designed for the easy and rapid development, generation, simulation, and discrimination of candidate models. The main idea of the program is to automatically create a defined set of model alternatives from a single master model. The user provides only one SBML-model and a set of directives from which the candidate models are created by leaving out species, modifiers or reactions. After generating models the software can automatically fit all these models to the data and provides a ranking for model selection, in case data is available. In contrast to other model generation programs, ModelMage aims at generating only a limited set of models that the user can precisely define. ModelMage uses COPASI as a simulation and optimization engine. Thus, all simulation and optimization features of COPASI are readily incorporated. ModelMage can be downloaded from http://sysbio.molgen.mpg.de/modelmage and is distributed as free software. PMID:19425122

  3. In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids

    Directory of Open Access Journals (Sweden)

    Ifedayo Victor Ogungbe

    2013-07-01

    Full Text Available Neglected Tropical Diseases (NTDs, like leishmaniasis, are major causes of mortality in resource-limited countries. The mortality associated with these diseases is largely due to fragile healthcare systems, lack of access to medicines, and resistance by the parasites to the few available drugs. Many antiparasitic plant-derived isoprenoids have been reported, and many of them have good in vitro activity against various forms of Leishmania spp. In this work, potential Leishmania biochemical targets of antiparasitic isoprenoids were studied in silico. Antiparasitic monoterpenoids selectively docked to L. infantum nicotinamidase, L. major uridine diphosphate-glucose pyrophosphorylase and methionyl t-RNA synthetase. The two protein targets selectively targeted by germacranolide sesquiterpenoids were L. major methionyl t-RNA synthetase and dihydroorotate dehydrogenase. Diterpenoids generally favored docking to L. mexicana glycerol-3-phosphate dehydrogenase. Limonoids also showed some selectivity for L. mexicana glycerol-3-phosphate dehydrogenase and L. major dihydroorotate dehydrogenase while withanolides docked more selectively with L. major uridine diphosphate-glucose pyrophosphorylase. The selectivity of the different classes of antiparasitic compounds for the protein targets considered in this work can be explored in fragment- and/or structure-based drug design towards the development of leads for new antileishmanial drugs.

  4. Staging of Prostate Cancer Using Automatic Feature Selection, Sampling and Dempster-Shafer Fusion

    Directory of Open Access Journals (Sweden)

    Sandeep Chandana

    2009-01-01

    Full Text Available A novel technique of automatically selecting the best pairs of features and sampling techniques to predict the stage of prostate cancer is proposed in this study. The problem of class imbalance, which is prominent in most medical data sets is also addressed here. Three feature subsets obtained by the use of principal components analysis (PCA, genetic algorithm (GA and rough sets (RS based approaches were also used in the study. The performance of under-sampling, synthetic minority over-sampling technique (SMOTE and a combination of the two were also investigated and the performance of the obtained models was compared. To combine the classifier outputs, we used the Dempster-Shafer (DS theory, whereas the actual choice of combined models was made using a GA. We found that the best performance for the overall system resulted from the use of under sampled data combined with rough sets based features modeled as a support vector machine (SVM.

  5. AUTOMATIC MODEL SELECTION FOR 3D RECONSTRUCTION OF BUILDINGS FROM SATELLITE IMAGARY

    Directory of Open Access Journals (Sweden)

    T. Partovi

    2013-09-01

    Full Text Available Through the improvements of satellite sensor and matching technology, the derivation of 3D models from space borne stereo data obtained a lot of interest for various applications such as mobile navigation, urban planning, telecommunication, and tourism. The automatic reconstruction of 3D building models from space borne point cloud data is still an active research topic. The challenging problem in this field is the relatively low quality of the Digital Surface Model (DSM generated by stereo matching of satellite data comparing to airborne LiDAR data. In order to establish an efficient method to achieve high quality models and complete automation from the mentioned DSM, in this paper a new method based on a model-driven strategy is proposed. For improving the results, refined orthorectified panchromatic images are introduced into the process as additional data. The idea of this method is based on ridge line extraction and analysing height values in direction of and perpendicular to the ridgeline direction. After applying pre-processing to the orthorectified data, some feature descriptors are extracted from the DSM, to improve the automatic ridge line detection. Applying RANSAC a line is fitted to each group of ridge points. Finally these ridge lines are refined by matching them or closing gaps. In order to select the type of roof model the heights of point in extension of the ridge line and height differences perpendicular to the ridge line are analysed. After roof model selection, building edge information is extracted from canny edge detection and parameters derived from the roof parts. Then the best model is fitted to extracted façade roofs based on detected type of model. Each roof is modelled independently and final 3D buildings are reconstructed by merging the roof models with the corresponding walls.

  6. Automatic Model Selection for 3d Reconstruction of Buildings from Satellite Imagary

    Science.gov (United States)

    Partovi, T.; Arefi, H.; Krauß, T.; Reinartz, P.

    2013-09-01

    Through the improvements of satellite sensor and matching technology, the derivation of 3D models from space borne stereo data obtained a lot of interest for various applications such as mobile navigation, urban planning, telecommunication, and tourism. The automatic reconstruction of 3D building models from space borne point cloud data is still an active research topic. The challenging problem in this field is the relatively low quality of the Digital Surface Model (DSM) generated by stereo matching of satellite data comparing to airborne LiDAR data. In order to establish an efficient method to achieve high quality models and complete automation from the mentioned DSM, in this paper a new method based on a model-driven strategy is proposed. For improving the results, refined orthorectified panchromatic images are introduced into the process as additional data. The idea of this method is based on ridge line extraction and analysing height values in direction of and perpendicular to the ridgeline direction. After applying pre-processing to the orthorectified data, some feature descriptors are extracted from the DSM, to improve the automatic ridge line detection. Applying RANSAC a line is fitted to each group of ridge points. Finally these ridge lines are refined by matching them or closing gaps. In order to select the type of roof model the heights of point in extension of the ridge line and height differences perpendicular to the ridge line are analysed. After roof model selection, building edge information is extracted from canny edge detection and parameters derived from the roof parts. Then the best model is fitted to extracted façade roofs based on detected type of model. Each roof is modelled independently and final 3D buildings are reconstructed by merging the roof models with the corresponding walls.

  7. Adaptive Robust Waveform Selection for Unknown Target Detection in Clutter

    Institute of Scientific and Technical Information of China (English)

    Lu-Lu Wang; Hong-Qiang Wang; Yu-Liang Qin; Yong-Qiang Cheng

    2014-01-01

    @@@A basic assumption of most recently proposed waveform design algorithms is that the target impulse response is a known deterministic function or a stochastic process with a known power spectral density (PSD). However, it is well-known that a target impulse response is neither easily nor accurately obtained; besides it changes sharply with attitude angles. Both of the aforementioned cases complicate the waveform design process. In this paper, an adaptive robust waveform selection method for unknown target detection in clutter is proposed. The target impulse response is considered to be unknown but belongs to a known uncertainty set. An adaptive waveform library is devised by using a signal-to-clutter-plus-noise ratio (SCNR)- based optimal waveform design method. By applying the minimax robust waveform selection method, the optimal robust waveform is selected to ensure the lowest performance bound of the unknown target detection in clutter. Results show that the adaptive waveform library outperforms the predefined linear frequency modulation (LFM) waveform library on the SCNR bound.

  8. Motor cortex guides selection of predictable movement targets

    Science.gov (United States)

    Woodgate, Philip J.W.; Strauss, Soeren; Sami, Saber A.; Heinke, Dietmar

    2016-01-01

    The present paper asks whether the motor cortex contributes to prediction-based guidance of target selection. This question was inspired by recent evidence that suggests (i) recurrent connections from the motor system into the attentional system may extract movement-relevant perceptual information and (ii) that the motor cortex cannot only generate predictions of the sensory consequences of movements but may also operate as predictor of perceptual events in general. To test this idea we employed a choice reaching task requiring participants to rapidly reach and touch a predictable or unpredictable colour target. Motor cortex activity was modulated via transcranial direct current stimulation (tDCS). In Experiment 1 target colour repetitions were predictable. Under such conditions anodal tDCS facilitated selection versus sham and cathodal tDCS. This improvement was apparent for trajectory curvature but not movement initiation. Conversely, where no predictability of colour was embedded reach performance was unaffected by tDCS. Finally, the results of a key-press experiment suggested that motor cortex involvement is restricted to tasks where the predictable target colour is movement-relevant. The outcomes are interpreted as evidence that the motor system contributes to the top-down guidance of selective attention to movement targets. PMID:25835319

  9. Classification and Target Group Selection Based Upon Frequent Patterns

    NARCIS (Netherlands)

    W.H.L.M. Pijls (Wim); R. Potharst (Rob)

    2000-01-01

    textabstractIn this technical report , two new algorithms based upon frequent patterns are proposed. One algorithm is a classification method. The other one is an algorithm for target group selection. In both algorithms, first of all, the collection of frequent patterns in the training set is constr

  10. Burglar Target Selection : A Cross-national Comparison

    NARCIS (Netherlands)

    Townsley, Michael; Birks, Daniel; Bernasco, Wim; Ruiter, Stijn; Johnson, Shane D.; White, Gentry; Baum, Scott

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both envi

  11. An algorithm for preferential selection of spectroscopic targets in LEGUE

    Institute of Scientific and Technical Information of China (English)

    Jeffrey L.Carlin; Carl J.Grillmair; Puragra Guhathakurta; Zhan-Wen Han; Jin-Liang Hou; Hsu-Tai Lee; Jing Li; Chao Liu; Xiao-Wei Liu; Kai-Ke Pan; J.A.Sellwood; Sébastien Lépine; Hong-Chi Wang; Fan Yang; Brian Yanny; Yue-Yang Zhang; Zheng Zheng; Zi Zhu; Heidi Jo Newberg; Li-Cai Deng; Timothy C.Beers; Yu-Qin Chen; Norbert Christlieb; Xiao-Ting Fu; Shuang Gao

    2012-01-01

    We describe a general target selection algorithm that is applicable to any survey in which the number of available candidates is much larger than the number of objects to be observed.This routine aims to achieve a balance between a smoothlyvarying,well-understood selection function and the desire to preferentially select certain types of targets.Some target-selection examples are shown that illustrate different possibilities of emphasis functions.Although it is generally applicable,the algorithm was developed specifically for the LAMOST Experiment for Galactic Understanding and Exploration(LEGUE)survey that will be carried out using the Chinese Guo Shou Jing Telescope.In particular,this algorithm was designed for the portion of LEGUE targeting the Galactic halo,in which we attempt to balance a variety of science goals that require stars at fainter magnitudes than can be completely sampled by LAMOST.This algorithm has been implemented for the halo portion of the LAMOST pilot survey,which began in October 2011.

  12. Integrative analysis to select cancer candidate biomarkers to targeted validation

    Science.gov (United States)

    Heberle, Henry; Domingues, Romênia R.; Granato, Daniela C.; Yokoo, Sami; Canevarolo, Rafael R.; Winck, Flavia V.; Ribeiro, Ana Carolina P.; Brandão, Thaís Bianca; Filgueiras, Paulo R.; Cruz, Karen S. P.; Barbuto, José Alexandre; Poppi, Ronei J.; Minghim, Rosane; Telles, Guilherme P.; Fonseca, Felipe Paiva; Fox, Jay W.; Santos-Silva, Alan R.; Coletta, Ricardo D.; Sherman, Nicholas E.; Paes Leme, Adriana F.

    2015-01-01

    Targeted proteomics has flourished as the method of choice for prospecting for and validating potential candidate biomarkers in many diseases. However, challenges still remain due to the lack of standardized routines that can prioritize a limited number of proteins to be further validated in human samples. To help researchers identify candidate biomarkers that best characterize their samples under study, a well-designed integrative analysis pipeline, comprising MS-based discovery, feature selection methods, clustering techniques, bioinformatic analyses and targeted approaches was performed using discovery-based proteomic data from the secretomes of three classes of human cell lines (carcinoma, melanoma and non-cancerous). Three feature selection algorithms, namely, Beta-binomial, Nearest Shrunken Centroids (NSC), and Support Vector Machine-Recursive Features Elimination (SVM-RFE), indicated a panel of 137 candidate biomarkers for carcinoma and 271 for melanoma, which were differentially abundant between the tumor classes. We further tested the strength of the pipeline in selecting candidate biomarkers by immunoblotting, human tissue microarrays, label-free targeted MS and functional experiments. In conclusion, the proposed integrative analysis was able to pre-qualify and prioritize candidate biomarkers from discovery-based proteomics to targeted MS. PMID:26540631

  13. Automatic Training Site Selection for Agricultural Crop Classification: a Case Study on Karacabey Plain, Turkey

    Science.gov (United States)

    Ozdarici Ok, A.; Akyurek, Z.

    2011-09-01

    This study implements a traditional supervised classification method to an optical image composed of agricultural crops by means of a unique way, selecting the training samples automatically. Panchromatic (1m) and multispectral (4m) Kompsat-2 images (July 2008) of Karacabey Plain (~100km2), located in Marmara region, are used to evaluate the proposed approach. Due to the characteristic of rich, loamy soils combined with reasonable weather conditions, the Karacabey Plain is one of the most valuable agricultural regions of Turkey. Analyses start with applying an image fusion algorithm on the panchromatic and multispectral image. As a result of this process, 1m spatial resolution colour image is produced. In the next step, the four-band fused (1m) image and multispectral (4m) image are orthorectified. Next, the fused image (1m) is segmented using a popular segmentation method, Mean- Shift. The Mean-Shift is originally a method based on kernel density estimation and it shifts each pixel to the mode of clusters. In the segmentation procedure, three parameters must be defined: (i) spatial domain (hs), (ii) range domain (hr), and (iii) minimum region (MR). In this study, in total, 176 parameter combinations (hs, hr, and MR) are tested on a small part of the area (~10km2) to find an optimum segmentation result, and a final parameter combination (hs=18, hr=20, and MR=1000) is determined after evaluating multiple goodness measures. The final segmentation output is then utilized to the classification framework. The classification operation is applied on the four-band multispectral image (4m) to minimize the mixed pixel effect. Before the image classification, each segment is overlaid with the bands of the image fused, and several descriptive statistics of each segment are computed for each band. To select the potential homogeneous regions that are eligible for the selection of training samples, a user-defined threshold is applied. After finding those potential regions, the

  14. A review of metaphase chromosome image selection techniques for automatic karyotype generation.

    Science.gov (United States)

    Arora, Tanvi; Dhir, Renu

    2016-08-01

    The karyotype is analyzed to detect the genetic abnormalities. It is generated by arranging the chromosomes after extracting them from the metaphase chromosome images. The chromosomes are non-rigid bodies that contain the genetic information of an individual. The metaphase chromosome image spread contains the chromosomes, but these chromosomes are not distinct bodies; they can either be individual chromosomes or be touching one another; they may be bent or even may be overlapping and thus forming a cluster of chromosomes. The extraction of chromosomes from these touching and overlapping chromosomes is a very tedious process. The segmentation of a random metaphase chromosome image may not give us correct and accurate results. Therefore, before taking up a metaphase chromosome image for analysis, it must be analyzed for the orientation of the chromosomes it contains. The various reported methods for metaphase chromosome image selection for automatic karyotype generation are compared in this paper. After analysis, it has been concluded that each metaphase chromosome image selection method has its advantages and disadvantages. PMID:26676686

  15. Target Selection for the SDSS-III MARVELS Survey

    OpenAIRE

    Paegert, Martin; Stassun, Keivan G.; De Lee, Nathan; Pepper, Joshua; Fleming, Scott W.; Sivarani, Thirupathi; Mahadevan, Suvrath; Mack III, Claude E.; Dhital, Saurav; Hebb, Leslie; Ge, Jian

    2015-01-01

    We present the target selection process for the Multi-object APO Radial Velocity Exoplanets Large-area Survey (MARVELS), which is part of the Sloan Digital Sky Survey (SDSS) III. MARVELS is a medium-resolution ($R \\sim 11000$) multi-fiber spectrograph capable of obtaining radial velocities for 60 objects at a time in order to find brown dwarfs and giant planets. The survey was configured to target dwarf stars with effective temperatures approximately between $4500$ and $6250 \\, \\mbox{K}$. For...

  16. Acoustic gaze adjustments during active target selection in echolocating porpoises.

    Science.gov (United States)

    Wisniewska, Danuta Maria; Johnson, Mark; Beedholm, Kristian; Wahlberg, Magnus; Madsen, Peter Teglberg

    2012-12-15

    Visually dominant animals use gaze adjustments to organize perceptual inputs for cognitive processing. Thereby they manage the massive sensory load from complex and noisy scenes. Echolocation, as an active sensory system, may provide more opportunities to control such information flow by adjusting the properties of the sound source. However, most studies of toothed whale echolocation have involved stationed animals in static auditory scenes for which dynamic information control is unnecessary. To mimic conditions in the wild, we designed an experiment with captive, free-swimming harbor porpoises tasked with discriminating between two hydrophone-equipped targets and closing in on the selected target; this allowed us to gain insight into how porpoises adjust their acoustic gaze in a multi-target dynamic scene. By means of synchronized cameras, an acoustic tag and on-target hydrophone recordings we demonstrate that porpoises employ both beam direction control and range-dependent changes in output levels and pulse intervals to accommodate their changing spatial relationship with objects of immediate interest. We further show that, when switching attention to another target, porpoises can set their depth of gaze accurately for the new target location. In combination, these observations imply that porpoises exert precise vocal-motor control that is tied to spatial perception akin to visual accommodation. Finally, we demonstrate that at short target ranges porpoises narrow their depth of gaze dramatically by adjusting their output so as to focus on a single target. This suggests that echolocating porpoises switch from a deliberative mode of sensorimotor operation to a reactive mode when they are close to a target. PMID:23175527

  17. Targets of balancing selection in the human genome

    DEFF Research Database (Denmark)

    Andrés, Aida M; Hubisz, Melissa J; Indap, Amit;

    2009-01-01

    to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism...... data set, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows...... enrichment in functional categories involved in cellular structure. Patterns are mostly concordant in the two populations, with a small fraction of genes showing population-specific signatures of selection. Power considerations indicate that our findings represent a subset of all targets in the genome...

  18. Nanostructured materials for selective recognition and targeted drug delivery

    International Nuclear Information System (INIS)

    Selective recognition requires the introduction of a molecular memory into a polymer matrix in order to make it capable of rebinding an analyte with a very high specificity. In addition, targeted drug delivery requires drug-loaded vesicles which preferentially localize to the sites of injury and avoid uptake into uninvolved tissues. The rapid evolution of nanotechnology is aiming to fulfill the goal of selective recognition and optimal drug delivery through the development of molecularly imprinted polymeric (MIP) nanoparticles, tailor-made for a diverse range of analytes (e.g., pharmaceuticals, pesticides, amino acids, etc.) and of nanostructured targeted drug carriers (e.g., liposomes and micelles) with increased circulation lifetimes. In the present study, PLGA microparticles containing multilamellar vesicles (MLVs), and MIP nanoparticles were synthesized to be employed as drug carriers and synthetic receptors respectively

  19. GIS (Geographic Information Systems) based automatic tool for selection of gas pipeline corridors

    Energy Technology Data Exchange (ETDEWEB)

    Matos, Denise F.; Menezes, Paulo Cesar P.; Paz, Luciana R.L.; Garcia, Katia C.; Cruz, Cristiane B.; Pires, Silvia H.M.; Damazio, Jorge M.; Medeiros, Alexandre M.

    2009-07-01

    This paper describes a methodology developed to build total accumulated surfaces in order to better select gas pipelines corridor alternatives. The methodology is based on the minimization of negative impacts and the use of Geographic Information Systems (GIS), allowing an automatic method of construction, evaluation and selection of alternatives, that will contribute to the decision making process. It is important to emphasize that this paper follows the assumptions presented on the research reports of a project sponsored by the Ministry of Mines and Energy (MME) and elaborated at the Electric Power Research Center (CEPEL), called 'Development of a Geographic Information System to Oil and Gas Sectors in Brazil', and also the studies d GTW Project (Gas to Wire). Gas pipelines, as for their linear characteristic, may cross a variety of habitats and settlements, increasing the complexity of their environmental management. Considering this reality, this paper presents a methodology that takes into account different environmental criteria (layers), according to the area impacted. From the synthesis of the criteria it is presented the total accumulated surface. It is showed an example of a hypothetical gas pipeline connection between two points using the total accumulated surface. To select the 'impact scores' of the features, the gas pipeline was considered as a linear feature, but the result is a region, formed by pixels, each pixel with an accumulated impact score lower than some arbitrary measure. This region is called 'corridor', and it is the final result obtained using the proposed methodology. (author)

  20. Selective Cell Targeting with Light-Absorbing Microparticles and Nanoparticles

    OpenAIRE

    Pitsillides, Costas M; Joe, Edwin K.; Wei, Xunbin; Anderson, R. Rox; Lin, Charles P.

    2003-01-01

    We describe a new method for selective cell targeting based on the use of light-absorbing microparticles and nanoparticles that are heated by short laser pulses to create highly localized cell damage. The method is closely related to chromophore-assisted laser inactivation and photodynamic therapy, but is driven solely by light absorption, without the need for photochemical intermediates (particularly singlet oxygen). The mechanism of light-particle interaction was investigated by nanosecond ...

  1. Selective Mitochondrial Targeting Exerts Anxiolytic Effects In Vivo.

    Science.gov (United States)

    Nussbaumer, Markus; Asara, John M; Teplytska, Larysa; Murphy, Michael P; Logan, Angela; Turck, Christoph W; Filiou, Michaela D

    2016-06-01

    Current treatment strategies for anxiety disorders are predominantly symptom-based. However, a third of anxiety patients remain unresponsive to anxiolytics highlighting the need for more effective, mechanism-based therapeutic approaches. We have previously compared high vs low anxiety mice and identified changes in mitochondrial pathways, including oxidative phosphorylation and oxidative stress. In this work, we show that selective pharmacological targeting of these mitochondrial pathways exerts anxiolytic effects in vivo. We treated high anxiety-related behavior (HAB) mice with MitoQ, an antioxidant that selectively targets mitochondria. MitoQ administration resulted in decreased anxiety-related behavior in HAB mice. This anxiolytic effect was specific for high anxiety as MitoQ treatment did not affect the anxiety phenotype of C57BL/6N and DBA/2J mouse strains. We furthermore investigated the molecular underpinnings of the MitoQ-driven anxiolytic effect and found that MitoQ treatment alters the brain metabolome and that the response to MitoQ treatment is characterized by distinct molecular signatures. These results indicate that a mechanism-driven approach based on selective mitochondrial targeting has the potential to attenuate the high anxiety phenotype in vivo, thus paving the way for translational implementation as long-term MitoQ administration is well-tolerated with no reported side effects in mice and humans. PMID:26567514

  2. TARGET SELECTION FOR THE LBTI EXOZODI KEY SCIENCE PROGRAM

    International Nuclear Information System (INIS)

    The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ∼300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions

  3. TARGET SELECTION FOR THE LBTI EXOZODI KEY SCIENCE PROGRAM

    Energy Technology Data Exchange (ETDEWEB)

    Weinberger, Alycia J. [Department of Terrestrial Magnetism, Carnegie Institution for Science, 5241 Broad Branch Road NW, Washington, DC 20015 (United States); Bryden, Geoff; Mennesson, Bertrand; Serabyn, Eugene [Jet Propulsion Laboratory, California Institute of Technology, 4800 Oak Grove Dr, Pasadena, CA 91109 (United States); Kennedy, Grant M.; Wyatt, Mark C. [Institute of Astronomy, University of Cambridge, Madingley Road, Cambridge CB3 0HA (United Kingdom); Roberge, Aki; Danchi, William C.; Stapelfeldt, Karl R. [Exoplanets and Stellar Astrophysics Laboratory, NASA Goddard Space Flight Center, Code 667, Greenbelt, MD 20771 (United States); Defrère, Denis; Hinz, Philip M.; Rieke, George; Bailey, Vanessa P.; Skemer, Andrew J. [Steward Observatory, University of Arizona, 933 North Cherry Lane, Tucson, AZ 85721 (United States); Millan-Gabet, Rafael [NASA Exoplanet Science Institute, California Institute of Technology, Pasadena, CA 91125 (United States); Haniff, Chris, E-mail: weinberger@dtm.ciw.edu [Cavendish Laboratory, University of Cambridge, JJ Thomson Avenue, Cambridge CB3 0HE (United Kingdom)

    2015-02-01

    The Hunt for Observable Signatures of Terrestrial planetary Systems (HOSTS) on the Large Binocular Telescope Interferometer will survey nearby stars for faint emission arising from ∼300 K dust (exozodiacal dust), and aims to determine the exozodiacal dust luminosity function. HOSTS results will enable planning for future space telescopes aimed at direct spectroscopy of habitable zone terrestrial planets, as well as greater understanding of the evolution of exozodiacal disks and planetary systems. We lay out here the considerations that lead to the final HOSTS target list. Our target selection strategy maximizes the ability of the survey to constrain the exozodi luminosity function by selecting a combination of stars selected for suitability as targets of future missions and as sensitive exozodi probes. With a survey of approximately 50 stars, we show that HOSTS can enable an understanding of the statistical distribution of warm dust around various types of stars and is robust to the effects of varying levels of survey sensitivity induced by weather conditions.

  4. Automatic online adaptive radiation therapy techniques for targets with significant shape change: a feasibility study

    Energy Technology Data Exchange (ETDEWEB)

    Court, Laurence E; Tishler, Roy B; Petit, Joshua; Cormack, Robert; Chin Lee [Department of Radiation Oncology, Dana-Farber/Brigham and Women' s Hospital Cancer Center, 75 Francis Street, ASBI-L2, Boston, MA 02115 (United States)

    2006-05-21

    This work looks at the feasibility of an online adaptive radiation therapy concept that would detect the daily position and shape of the patient, and would then correct the daily treatment to account for any changes compared with planning position. In particular, it looks at the possibility of developing algorithms to correct for large complicated shape change. For co-planar beams, the dose in an axial plane is approximately associated with the positions of a single multi-leaf collimator (MLC) pair. We start with a primary plan, and automatically generate several secondary plans with gantry angles offset by regular increments. MLC sequences for each plan are calculated keeping monitor units (MUs) and number of segments constant for a given beam (fluences are different). Bulk registration (3D) of planning and daily CT images gives global shifts. Slice-by-slice (2D) registration gives local shifts and rotations about the longitudinal axis for each axial slice. The daily MLC sequence is then created for each axial slice/MLC leaf pair combination, by taking the MLC positions from the pre-calculated plan with the nearest rotation, and shifting using a beam's-eye-view calculation to account for local linear shifts. A planning study was carried out using two head and neck region MR images of a healthy volunteer which were contoured to simulate a base-of-tongue treatment: one with the head straight (used to simulate the planning image) and the other with the head tilted to the left (the daily image). Head and neck treatment was chosen to evaluate this technique because of its challenging nature, with varying internal and external contours, and multiple degrees of freedom. Shape change was significant: on a slice-by-slice basis, local rotations in the daily image varied from 2 to 31 deg, and local shifts ranged from -0.2 to 0.5 cm and -0.4 to 0.0 cm in right-left and posterior-anterior directions, respectively. The adapted treatment gave reasonable target coverage (100

  5. A Deterministic Approach to Active Debris Removal Target Selection

    Science.gov (United States)

    Lidtke, A.; Lewis, H.; Armellin, R.

    2014-09-01

    Many decisions, with widespread economic, political and legal consequences, are being considered based on space debris simulations that show that Active Debris Removal (ADR) may be necessary as the concerns about the sustainability of spaceflight are increasing. The debris environment predictions are based on low-accuracy ephemerides and propagators. This raises doubts about the accuracy of those prognoses themselves but also the potential ADR target-lists that are produced. Target selection is considered highly important as removal of many objects will increase the overall mission cost. Selecting the most-likely candidates as soon as possible would be desirable as it would enable accurate mission design and allow thorough evaluation of in-orbit validations, which are likely to occur in the near-future, before any large investments are made and implementations realized. One of the primary factors that should be used in ADR target selection is the accumulated collision probability of every object. A conjunction detection algorithm, based on the smart sieve method, has been developed. Another algorithm is then applied to the found conjunctions to compute the maximum and true probabilities of collisions taking place. The entire framework has been verified against the Conjunction Analysis Tools in AGIs Systems Toolkit and relative probability error smaller than 1.5% has been achieved in the final maximum collision probability. Two target-lists are produced based on the ranking of the objects according to the probability they will take part in any collision over the simulated time window. These probabilities are computed using the maximum probability approach, that is time-invariant, and estimates of the true collision probability that were computed with covariance information. The top-priority targets are compared, and the impacts of the data accuracy and its decay are highlighted. General conclusions regarding the importance of Space Surveillance and Tracking for the

  6. Dolphin: a tool for automatic targeted metabolite profiling using 1D and 2D (1)H-NMR data.

    Science.gov (United States)

    Gómez, Josep; Brezmes, Jesús; Mallol, Roger; Rodríguez, Miguel A; Vinaixa, Maria; Salek, Reza M; Correig, Xavier; Cañellas, Nicolau

    2014-12-01

    One of the main challenges in nuclear magnetic resonance (NMR) metabolomics is to obtain valuable metabolic information from large datasets of raw NMR spectra in a high throughput, automatic, and reproducible way. To date, established software packages used to match and quantify metabolites in NMR spectra remain mostly manually operated, leading to low resolution results and subject to inconsistencies not attributable to the NMR technique itself. Here, we introduce a new software package, called Dolphin, able to automatically quantify a set of target metabolites in multiple sample measurements using an approach based on 1D and 2D NMR techniques to overcome the inherent limitations of 1D (1)H-NMR spectra in metabolomics. Dolphin takes advantage of the 2D J-resolved NMR spectroscopy signal dispersion to avoid inconsistencies in signal position detection, enhancing the reliability and confidence in metabolite matching. Furthermore, in order to improve accuracy in quantification, Dolphin uses 2D NMR spectra to obtain additional information on all neighboring signals surrounding the target metabolite. We have compared the targeted profiling results of Dolphin, recorded from standard biological mixtures, with those of two well established approaches in NMR metabolomics. Overall, Dolphin produced more accurate results with the added advantage of being a fully automated and high throughput processing package. PMID:25370160

  7. Automatic localization of target vertebrae in spine surgery using fast CT-to-fluoroscopy (3D-2D) image registration

    Science.gov (United States)

    Otake, Y.; Schafer, S.; Stayman, J. W.; Zbijewski, W.; Kleinszig, G.; Graumann, R.; Khanna, A. J.; Siewerdsen, J. H.

    2012-02-01

    Localization of target vertebrae is an essential step in minimally invasive spine surgery, with conventional methods relying on "level counting" - i.e., manual counting of vertebrae under fluoroscopy starting from readily identifiable anatomy (e.g., the sacrum). The approach requires an undesirable level of radiation, time, and is prone to counting errors due to the similar appearance of vertebrae in projection images; wrong-level surgery occurs in 1 of every ~3000 cases. This paper proposes a method to automatically localize target vertebrae in x-ray projections using 3D-2D registration between preoperative CT (in which vertebrae are preoperatively labeled) and intraoperative fluoroscopy. The registration uses an intensity-based approach with a gradient-based similarity metric and the CMA-ES algorithm for optimization. Digitally reconstructed radiographs (DRRs) and a robust similarity metric are computed on GPU to accelerate the process. Evaluation in clinical CT data included 5,000 PA and LAT projections randomly perturbed to simulate human variability in setup of mobile intraoperative C-arm. The method demonstrated 100% success for PA view (projection error: 0.42mm) and 99.8% success for LAT view (projection error: 0.37mm). Initial implementation on GPU provided automatic target localization within about 3 sec, with further improvement underway via multi-GPU. The ability to automatically label vertebrae in fluoroscopy promises to streamline surgical workflow, improve patient safety, and reduce wrong-site surgeries, especially in large patients for whom manual methods are time consuming and error prone.

  8. Highly selective luminescent nanostructures for mitochondrial imaging and targeting

    Science.gov (United States)

    Fanizza, E.; Iacobazzi, R. M.; Laquintana, V.; Valente, G.; Caliandro, G.; Striccoli, M.; Agostiano, A.; Cutrignelli, A.; Lopedota, A.; Curri, M. L.; Franco, M.; Depalo, N.; Denora, N.

    2016-02-01

    Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino functionalized luminescent silica coated QD nanoparticles (QD@SiO2 NPs) provides a versatile nanoplatform to anchor a potent and selective TSPO ligand, characterized by a 2-phenyl-imidazo[1,2-a]pyridine acetamide structure along with a derivatizable carboxylic end group, useful to conjugate the TSPO ligand and achieve TSPO-QD@SiO2 NPs by means of a covalent amide bond. The colloidal stability and optical properties of the proposed nanomaterials are comprehensively investigated and their potential as mitochondrial imaging agents is fully assessed. Sub-cellular fractionation, together with confocal laser scanning fluorescence microscopy and co-localization analysis of targeted TSPO-QD@SiO2 NPs in C6 glioma cells overexpressing the TSPO, proves the great potential of these multifunctional nanosystems as in vitro selective mitochondrial imaging agents.Here a luminescent hybrid nanostructure based on functionalized quantum dots (QDs) is used as a fluorescent imaging agent able to target selectively mitochondria thanks to the molecular recognition of the translocator protein (TSPO). The selective targeting of such an 18 kDa protein mainly located in the outer mitochondrial membrane and overexpressed in several pathological states including neurodegenerative diseases and cancers may provide valuable information for the early diagnosis and therapy of human disorders. In particular, the rational design of amino

  9. Comparison of different automatic adaptive threshold selection techniques for estimating discharge from river width

    Science.gov (United States)

    Elmi, Omid; Javad Tourian, Mohammad; Sneeuw, Nico

    2015-04-01

    The importance of river discharge monitoring is critical for e.g., water resource planning, climate change, hazard monitoring. River discharge has been measured at in situ gauges for more than a century. Despite various attempts, some basins are still ungauged. Moreover, a reduction in the number of worldwide gauging stations increases the interest to employ remote sensing data for river discharge monitoring. Finding an empirical relationship between simultaneous in situ measurements of discharge and river widths derived from satellite imagery has been introduced as a straightforward remote sensing alternative. Classifying water and land in an image is the primary task for defining the river width. Water appears dark in the near infrared and infrared bands in satellite images. As a result low values in the histogram usually represent the water content. In this way, applying a threshold on the image histogram and separating into two different classes is one of the most efficient techniques to build a water mask. Beside its simple definition, finding the appropriate threshold value in each image is the most critical issue. The threshold is variable due to changes in the water level, river extent, atmosphere, sunlight radiation, onboard calibration of the satellite over time. These complexities in water body classification are the main source of error in river width estimation. In this study, we are looking for the most efficient adaptive threshold algorithm to estimate the river discharge. To do this, all cloud free MODIS images coincident with the in situ measurement are collected. Next a number of automatic threshold selection techniques are employed to generate different dynamic water masks. Then, for each of them a separate empirical relationship between river widths and discharge measurements are determined. Through these empirical relationships, we estimate river discharge at the gauge and then validate our results against in situ measurements and also

  10. Dynamic interactions between visual working memory and saccade target selection.

    Science.gov (United States)

    Schneegans, Sebastian; Spencer, John P; Schöner, Gregor; Hwang, Seongmin; Hollingworth, Andrew

    2014-01-01

    Recent psychophysical experiments have shown that working memory for visual surface features interacts with saccadic motor planning, even in tasks where the saccade target is unambiguously specified by spatial cues. Specifically, a match between a memorized color and the color of either the designated target or a distractor stimulus influences saccade target selection, saccade amplitudes, and latencies in a systematic fashion. To elucidate these effects, we present a dynamic neural field model in combination with new experimental data. The model captures the neural processes underlying visual perception, working memory, and saccade planning relevant to the psychophysical experiment. It consists of a low-level visual sensory representation that interacts with two separate pathways: a spatial pathway implementing spatial attention and saccade generation, and a surface feature pathway implementing color working memory and feature attention. Due to bidirectional coupling between visual working memory and feature attention in the model, the working memory content can indirectly exert an effect on perceptual processing in the low-level sensory representation. This in turn biases saccadic movement planning in the spatial pathway, allowing the model to quantitatively reproduce the observed interaction effects. The continuous coupling between representations in the model also implies that modulation should be bidirectional, and model simulations provide specific predictions for complementary effects of saccade target selection on visual working memory. These predictions were empirically confirmed in a new experiment: Memory for a sample color was biased toward the color of a task-irrelevant saccade target object, demonstrating the bidirectional coupling between visual working memory and perceptual processing. PMID:25228628

  11. Automatic air cargo selection and weight balancing: A mixed integer programming approach

    OpenAIRE

    Vancroonenburg, Wim; Verstichel, Jannes; Tavernier, Karel; Vanden Berghe, Greet

    2014-01-01

    The present contribution introduces a mixed integer linear programming model as a decision support tool for air cargo load planning. The main objective for the model is to find the most profitable selection from a set of cargo to be loaded on an aircraft. The secondary objective is to minimize the deviation between the aircraft’s centre of gravity, and a known target value so as to reduce fuel consumption and improve stability. The model is subject to a large number of constraints that ensure...

  12. Theater targets plume edge extraction and hardbody aimpoint selection using morphological image processing

    Science.gov (United States)

    Paiva, Clifford A.

    1997-06-01

    (U) Future successful ballistic missile booster intercepts will require advanced automatic target detection, tracking, classification and identification (ADTCI) image processing techniques. Two such techniques are presented in this classified SECRET paper using the synthetic scene generator model (SSGM) in combination with the advanced systems (AVS) image processing package. Two challenging multispectral cases are treated: (1) missile hardbody occultation by the missile exhaust plume, and (2) variable plume/hardbody system (PHS) gradient intensities generated by missile tumbling due to exiting the sensible atmosphere. The target detection, tracking and edge extraction methods selected for this study include morphological, open-close operations within decision- level fusion for the obscuration case and pixel-level fusion for variable edge intensities. Other investigators have approached this issue on similar image processing techniques. The multispectral (2.69 - 2.95 micrometer SWIR; 4.17 - 4.2, 4.35 - 4.50 micrometer MWIR; and 8.0 - 12.0 micrometer LWIR) target/background imagery includes SWIRM/MWIR boost phase track (with occlusion problem) and LWIR aimpoint selection (with tumbling problem). The two classified missile systems are: (1) a depressed-angle submarine launched ballistic missile (SLBM) and (2) a medium range ballistic missile (MRBM). The results indicate that for 6 degrees of freedom (6 DOF) hardbodies, ATDCI geometrical pattern reference libraries should be optimized to accommodate the extreme variable gradient geometries for tumbling midcourse targets. For boost- phase missile hardbody occultation by missile exhaust plumes, segmentation and feature extraction should be implemented in each bandpass before processing to the ATDCI classifier. This study demonstrates that although the plume/hardbody system edges were extracted, the geometry of the target edge often deviated from symmetry.

  13. Target inhibition networks: predicting selective combinations of druggable targets to block cancer survival pathways.

    Directory of Open Access Journals (Sweden)

    Jing Tang

    Full Text Available A recent trend in drug development is to identify drug combinations or multi-target agents that effectively modify multiple nodes of disease-associated networks. Such polypharmacological effects may reduce the risk of emerging drug resistance by means of attacking the disease networks through synergistic and synthetic lethal interactions. However, due to the exponentially increasing number of potential drug and target combinations, systematic approaches are needed for prioritizing the most potent multi-target alternatives on a global network level. We took a functional systems pharmacology approach toward the identification of selective target combinations for specific cancer cells by combining large-scale screening data on drug treatment efficacies and drug-target binding affinities. Our model-based prediction approach, named TIMMA, takes advantage of the polypharmacological effects of drugs and infers combinatorial drug efficacies through system-level target inhibition networks. Case studies in MCF-7 and MDA-MB-231 breast cancer and BxPC-3 pancreatic cancer cells demonstrated how the target inhibition modeling allows systematic exploration of functional interactions between drugs and their targets to maximally inhibit multiple survival pathways in a given cancer type. The TIMMA prediction results were experimentally validated by means of systematic siRNA-mediated silencing of the selected targets and their pairwise combinations, showing increased ability to identify not only such druggable kinase targets that are essential for cancer survival either individually or in combination, but also synergistic interactions indicative of non-additive drug efficacies. These system-level analyses were enabled by a novel model construction method utilizing maximization and minimization rules, as well as a model selection algorithm based on sequential forward floating search. Compared with an existing computational solution, TIMMA showed both enhanced

  14. Development of hematin conjugated PLGA nanoparticle for selective cancer targeting.

    Science.gov (United States)

    Amin, Md Lutful; Kim, Dami; Kim, SeJin

    2016-08-25

    Targeted nanomedicine for cancer therapy has gained widespread popularity and is being extensively explored. Porphyrins have intrinsic tumor localizing ability and have been studied for photodynamic therapy. However, they have not been used as cancer targeting agents for nanomedicines. In this study, PLGA nanoparticles were formulated and an iron-containing blood porphyrin, hematin was conjugated to the surface of the nanoparticles to investigate selectivity towards cancer cell and cellular internalization. Hematin was previously shown to facilitate growth and proliferation of cancer cells. PLGA nanoparticles were characterized by FE-SEM, AFM, DLS, and Zeta potential analyzer. The conjugation of hematin was confirmed by FTIR. HeLa cells were used to study tumor selectivity and uptake. Hematin conjugated particles (ζ potential: -15.19mV) showed higher affinity towards the cancer cells than the control particles. The result indicated that the particles were internalized by heme carrier protein-1. Together these data suggest that hematin is a promising cancer targeting material for nanotherapeutics. PMID:27260086

  15. Automatic Shape-Based Target Extraction for Close-Range Photogrammetry

    Science.gov (United States)

    Guo, X.; Chen, Y.; Wang, C.; Cheng, M.; Wen, C.; Yu, J.

    2016-06-01

    In order to perform precise identification and location of artificial coded targets in natural scenes, a novel design of circle-based coded target and the corresponding coarse-fine extraction algorithm are presented. The designed target separates the target box and coding box totally and owns an advantage of rotation invariance. Based on the original target, templates are prepared by three geometric transformations and are used as the input of shape-based template matching. Finally, region growing and parity check methods are used to extract the coded targets as final results. No human involvement is required except for the preparation of templates and adjustment of thresholds in the beginning, which is conducive to the automation of close-range photogrammetry. The experimental results show that the proposed recognition method for the designed coded target is robust and accurate.

  16. Engineering novel cell surface chemistry for selective tumor cell targeting

    Energy Technology Data Exchange (ETDEWEB)

    Bertozzi, C.R. [Univ. of California, Berkeley, CA (United States)]|[Lawrence Berkeley National Lab., CA (United States)

    1997-12-31

    A common feature of many different cancers is the high expression level of the two monosaccharides sialic acid and fucose within the context of cell-surface associated glycoconjugates. A correlation has been made between hypersialylation and/or hyperfucosylation and the highly metastatic phenotype. Thus, a targeting strategy based on sialic acid or fucose expression would be a powerful tool for the development of new cancer cell-selective therapies and diagnostic agents. We have discovered that ketone groups can be incorporated metabolically into cell-surface associated sialic acids. The ketone is can be covalently ligated with hydrazide functionalized proteins or small molecules under physiological conditions. Thus, we have discovered a mechanism to selectively target hydrazide conjugates to highly sialylated cells such as cancer cells. Applications of this technology to the generation of novel cancer cell-selective toxins and MRI contrast reagents will be discussed, in addition to progress towards the use of cell surface fucose residues as vehicles for ketone expression.

  17. Selective Induction of Cancer Cell Death by Targeted Granzyme B

    Directory of Open Access Journals (Sweden)

    Robert A. Jabulowsky

    2013-02-01

    Full Text Available The potential utility of immunotoxins for cancer therapy has convincingly been demonstrated in clinical studies. Nevertheless, the high immunogenicity of their bacterial toxin domain represents a critical limitation, and has prompted the evaluation of cell-death inducing proteins of human origin as a basis for less immunogenic immunotoxin-like molecules. In this review, we focus on the current status and future prospects of targeted fusion proteins for cancer therapy that employ granzyme B (GrB from cytotoxic lymphocytes as a cytotoxic moiety. Naturally, this serine protease plays a critical role in the immune defense by inducing apoptotic target cell death upon cleavage of intracellular substrates. Advances in understanding of the structure and function of GrB enabled the generation of chimeric fusion proteins that carry a heterologous cell binding domain for recognition of tumor-associated cell surface antigens. These hybrid molecules display high selectivity for cancer cells, with cell killing activities similar to that of corresponding recombinant toxins. Recent findings have helped to understand and circumvent intrinsic cell binding of GrB and susceptibility of the enzyme to inhibition by serpins. This now allows the rational design of optimized GrB derivatives that avoid sequestration by binding to non-target tissues, limit off-target effects, and overcome resistance mechanisms in tumor cells.

  18. Selective follicular targeting by modification of the particle sizes.

    Science.gov (United States)

    Patzelt, Alexa; Richter, Heike; Knorr, Fanny; Schäfer, Ulrich; Lehr, Claus-Michael; Dähne, Lars; Sterry, Wolfram; Lademann, Juergen

    2011-02-28

    Hair follicles represent interesting target sites for topically applied substances such as topical vaccinations or agents used in the field of regenerative medicine. In recent years, it could be shown that particles penetrate very effectively into the hair follicles. In the present study, the influence of particle size on the follicular penetration depths was examined. The penetration depths of two different types of particles sized 122 to 1000 nm were determined in vitro on porcine skin. The results revealed that the particles of medium size (643 and 646 nm, respectively) penetrated deeper into the porcine hair follicles than smaller or larger particles. It was concluded that by varying the particle size, different sites within the porcine hair follicle can be targeted selectively. For the human terminal hair follicle, the situation can be expected to be similar due to a similar size ratio of the hair follicles. PMID:21087645

  19. Automatic Target Recognition in Synthetic Aperture Sonar Images Based on Geometrical Feature Extraction

    OpenAIRE

    J. Del Rio Vera; Coiras, E.; Groen, J; Evans, B.

    2009-01-01

    This paper presents a new supervised classification approach for automated target recognition (ATR) in SAS images. The recognition procedure starts with a novel segmentation stage based on the Hilbert transform. A number of geometrical features are then extracted and used to classify observed objects against a previously compiled database of target and non-target features. The proposed approach has been tested on a set of 1528 simulated images created by the NURC SIGMAS sonar model, achieving...

  20. Automatic Target Recognition in Synthetic Aperture Sonar Images Based on Geometrical Feature Extraction

    Science.gov (United States)

    Del Rio Vera, J.; Coiras, E.; Groen, J.; Evans, B.

    2009-12-01

    This paper presents a new supervised classification approach for automated target recognition (ATR) in SAS images. The recognition procedure starts with a novel segmentation stage based on the Hilbert transform. A number of geometrical features are then extracted and used to classify observed objects against a previously compiled database of target and non-target features. The proposed approach has been tested on a set of 1528 simulated images created by the NURC SIGMAS sonar model, achieving up to 95% classification accuracy.

  1. Validation of experts versus atlas-based and automatic registration methods for subthalamic nucleus targeting on MRI

    International Nuclear Information System (INIS)

    Objects: In functional stereotactic neurosurgery, one of the cornerstones upon which the success and the operating time depends is an accurate targeting. The subthalamic nucleus (STN) is the usual target involved when applying deep brain stimulation for Parkinson's disease (PD). Unfortunately, STN is usually not clearly visible in common medical imaging modalities, which justifies the use of atlas-based segmentation techniques to infer the STN location. Materials and methods: Eight bilaterally implanted PD patients were included in this study. A three-dimensional T1-weighted sequence and inversion recovery T2-weighted coronal slices were acquired pre-operatively. We propose a methodology for the construction of a ground truth of the STN location and a scheme that allows both, to perform a comparison between different non-rigid registration algorithms and to evaluate their usability to locate the STN automatically. Results: The intra-expert variability in identifying the STN location is 1.06±0.61 mm while the best non-rigid registration method gives an error of 1.80±0.62 mm. On the other hand, statistical tests show that an affine registration with only 12 degrees of freedom is not enough for this application. Conclusions: Using our validation-evaluation scheme, we demonstrate that automatic STN localization is possible and accurate with non-rigid registration algorithms. (orig.)

  2. Oncotripsy: Targeting cancer cells selectively via resonant harmonic excitation

    CERN Document Server

    Heyden, Stefanie

    2015-01-01

    We investigate a method of selectively targeting cancer cells by means of ultrasound harmonic excitation at their resonance frequency, which we refer to as oncotripsy. The geometric model of the cells takes into account the cytoplasm, nucleus and nucleolus, as well as the plasma membrane and nuclear envelope. Material properties are varied within a pathophysiologically-relevant range. A first modal analysis reveals the existence of a spectral gap between the natural frequencies and, most importantly, resonant growth rates of healthy and cancerous cells. The results of the modal analysis are verified by simulating the fully-nonlinear transient response of healthy and cancerous cells at resonance. The fully nonlinear analysis confirms that cancerous cells can be selectively taken to lysis by the application of carefully tuned ultrasound harmonic excitation while simultaneously leaving healthy cells intact.

  3. Oncotripsy: Targeting cancer cells selectively via resonant harmonic excitation

    Science.gov (United States)

    Heyden, S.; Ortiz, M.

    2016-07-01

    We investigate a method of selectively targeting cancer cells by means of ultrasound harmonic excitation at their resonance frequency, which we refer to as oncotripsy. The geometric model of the cells takes into account the cytoplasm, nucleus and nucleolus, as well as the plasma membrane and nuclear envelope. Material properties are varied within a pathophysiologically-relevant range. A first modal analysis reveals the existence of a spectral gap between the natural frequencies and, most importantly, resonant growth rates of healthy and cancerous cells. The results of the modal analysis are verified by simulating the fully-nonlinear transient response of healthy and cancerous cells at resonance. The fully nonlinear analysis confirms that cancerous cells can be selectively taken to lysis by the application of carefully tuned ultrasound harmonic excitation while simultaneously leaving healthy cells intact.

  4. Recombinant protein expression by targeting pre-selected chromosomal loci

    Directory of Open Access Journals (Sweden)

    Krömer Wolfgang

    2009-12-01

    Full Text Available Abstract Background Recombinant protein expression in mammalian cells is mostly achieved by stable integration of transgenes into the chromosomal DNA of established cell lines. The chromosomal surroundings have strong influences on the expression of transgenes. The exploitation of defined loci by targeting expression constructs with different regulatory elements is an approach to design high level expression systems. Further, this allows to evaluate the impact of chromosomal surroundings on distinct vector constructs. Results We explored antibody expression upon targeting diverse expression constructs into previously tagged loci in CHO-K1 and HEK293 cells that exhibit high reporter gene expression. These loci were selected by random transfer of reporter cassettes and subsequent screening. Both, retroviral infection and plasmid transfection with eGFP or antibody expression cassettes were employed for tagging. The tagged cell clones were screened for expression and single copy integration. Cell clones producing > 20 pg/cell in 24 hours could be identified. Selected integration sites that had been flanked with heterologous recombinase target sites (FRTs were targeted by Flp recombinase mediated cassette exchange (RMCE. The results give proof of principle for consistent protein expression upon RMCE. Upon targeting antibody expression cassettes 90-100% of all resulting cell clones showed correct integration. Antibody production was found to be highly consistent within the individual cell clones as expected from their isogenic nature. However, the nature and orientation of expression control elements revealed to be critical. The impact of different promoters was examined with the tag-and-targeting approach. For each of the chosen promoters high expression sites were identified. However, each site supported the chosen promoters to a different extent, indicating that the strength of a particular promoter is dominantly defined by its chromosomal context

  5. The SAMI Galaxy Survey: instrument specification and target selection

    CERN Document Server

    Bryant, J J; Robotham, A S G; Croom, S M; Driver, S P; Drinkwater, M J; Lorente, N P F; Cortese, L; Scott, N; Colless, M; Schaefer, A; Taylor, E N; Konstantopoulos, I S; Allen, J T; Baldry, I; Barnes, L; Bauer, A E; Bland-Hawthorn, J; Bloom, J V; Brooks, A M; Brough, S; Cecil, G; Couch, W; Croton, D; Davies, R; Ellis, S; Fogarty, L M R; Foster, C; Glazebrook, K; Goodwin, M; Green, A; Gunawardhana, M L; Hampton, E; Ho, I -T; Hopkins, A M; Kewley, L; Lawrence, J S; Leon-Saval, S G; Leslie, S; Lewis, G; Liske, J; Lopez-Sanchez, A R; Mahajan, S; Medling, A M; Metcalfe, N; Meyer, M; Mould, J; Obreschkow, D; O'Toole, S; Pracy, M; Richards, S N; Shanks, T; Sharp, R; Sweet, S M; Thomas, A D; Tonini, C; Walcher, C J

    2014-01-01

    The SAMI Galaxy Survey will observe 3400 galaxies with the Sydney-AAO Multi-object Integral-field spectrograph (SAMI) on the Anglo-Australian Telescope (AAT) in a 3-year survey which began in 2013. We present the throughput of the SAMI system, the science basis and specifications for the target selection, the survey observation plan and the combined properties of the selected galaxies. The survey includes four volume limited galaxy samples based on cuts in a proxy for stellar mass, along with low-stellar mass dwarf galaxies all selected from the Galaxy And Mass Assembly (GAMA) survey. The GAMA regions were selected because of the vast array of ancillary data available, including ultraviolet through to radio bands. These fields are on the celestial equator at 9, 12, and 14.5 hours, and cover a total of 144 square degrees (in GAMA-I). Higher density environments are also included with the addition of eight clusters. The clusters have spectroscopy from 2dFGRS and SDSS and photometry in regions covered by the Slo...

  6. Target Selection for the SDSS-III MARVELS Survey

    CERN Document Server

    Paegert, Martin; De Lee, Nathan; Pepper, Joshua; Fleming, Scott W; Sivarani, Thirupathi; Mahadevan, Suvrath; Mack, Claude E; Dhital, Saurav; Hebb, Leslie; Ge, Jian

    2015-01-01

    We present the target selection process for the Multi-object APO Radial Velocity Exoplanets Large-area Survey (MARVELS), which is part of the Sloan Digital Sky Survey (SDSS) III. MARVELS is a medium-resolution ($R \\sim 11000$) multi-fiber spectrograph capable of obtaining radial velocities for 60 objects at a time in order to find brown dwarfs and giant planets. The survey was configured to target dwarf stars with effective temperatures approximately between $4500$ and $6250 \\, \\mbox{K}$. For the first 2 years MARVELS relied on low-resolution spectroscopic pre-observations to estimate the effective temperature and $\\log(g)$ for candidate stars and then selected suitable dwarf stars from this pool. Ultimately, the pre-observation spectra proved ineffective at filtering out giant stars; many giants were incorrectly classified as dwarfs, resulting in a giant contamination rate of $\\sim$30\\% for the first phase of the MARVELS survey. Thereafter, the survey instead applied a reduced proper motion cut to eliminate ...

  7. Positive-negative-selection-mediated gene targeting in rice

    Directory of Open Access Journals (Sweden)

    Zenpei eShimatani

    2015-01-01

    Full Text Available Gene targeting (GT refers to the designed modification of genomic sequence(s through homologous recombination (HR. GT is a powerful tool both for the study of gene function and for molecular breeding. However, in transformation of higher plants, non-homologous end joining (NHEJ occurs overwhelmingly in somatic cells, masking HR-mediated GT. Positive-negative selection (PNS is an approach for finding HR-mediated GT events because it can eliminate NHEJ effectively by expression of a negative-selection marker gene. In rice—a major crop worldwide—reproducible PNS-mediated GT of endogenous genes has now been successfully achieved. The procedure is based on strong PNS using diphtheria toxin A-fragment as a negative marker, and has succeeded in the directed modification of several endogenous rice genes in various ways. In addition to gene knock-outs and knock-ins, a nucleotide substitution in a target gene was also achieved recently. This review presents a summary of the development of the rice PNS system, highlighting its advantages. Different types of gene modification and gene editing aimed at developing new plant breeding technology (NPBT based on PNS are discussed.

  8. Evaluation of the use of automatic exposure control and automatic tube potential selection in low-dose cerebrospinal fluid shunt head CT

    Energy Technology Data Exchange (ETDEWEB)

    Wallace, Adam N.; Bagade, Swapnil; Chatterjee, Arindam; Hicks, Brandon; McKinstry, Robert C. [Barnes Jewish Hospital, Mallinckrodt Institute of Radiology, St. Louis, MO (United States); Washington University School of Medicine, St. Louis, MO (United States); Vyhmeister, Ross [Washington University School of Medicine, St. Louis, MO (United States); Ramirez-Giraldo, Juan Carlos [Siemens Healthcare, Malvern, PA (United States)

    2015-03-17

    Cerebrospinal fluid shunts are primarily used for the treatment of hydrocephalus. Shunt complications may necessitate multiple non-contrast head CT scans resulting in potentially high levels of radiation dose starting at an early age. A new head CT protocol using automatic exposure control and automated tube potential selection has been implemented at our institution to reduce radiation exposure. The purpose of this study was to evaluate the reduction in radiation dose achieved by this protocol compared with a protocol with fixed parameters. A retrospective sample of 60 non-contrast head CT scans assessing for cerebrospinal fluid shunt malfunction was identified, 30 of which were performed with each protocol. The radiation doses of the two protocols were compared using the volume CT dose index and dose length product. The diagnostic acceptability and quality of each scan were evaluated by three independent readers. The new protocol lowered the average volume CT dose index from 15.2 to 9.2 mGy representing a 39 % reduction (P < 0.01; 95 % CI 35-44 %) and lowered the dose length product from 259.5 to 151.2 mGy/cm representing a 42 % reduction (P < 0.01; 95 % CI 34-50 %). The new protocol produced diagnostically acceptable scans with comparable image quality to the fixed parameter protocol. A pediatric shunt non-contrast head CT protocol using automatic exposure control and automated tube potential selection reduced patient radiation dose compared with a fixed parameter protocol while producing diagnostic images of comparable quality. (orig.)

  9. Using Fuzzy Modifier in Similarity Measure of Fuzzy Attribute Graph and Its Automatic Selection in Structural Pattern Recognition

    OpenAIRE

    Payman Moallem

    2007-01-01

    Fuzzy Attribute Graph (FAG) is a powerful tool for representation and recognition of structural patterns. The conventional framework for similarity measure of FAGs is based on equivalent fuzzy attributes but in fuzzy world, some attributes are more important. In this paper, a modified recognition framework, using linguistic modifier for matching of the fuzzy attribute graphs, is introduced. Then an algorithm for automatic selection of fuzzy modifier based on the learning patterns is posed. So...

  10. Landslide susceptibility mapping in three selected target zones in Afghanistan

    Science.gov (United States)

    Schwanghart, Wolfgang; Seegers, Joe; Zeilinger, Gerold

    2015-04-01

    In May 2014, a large and mobile landslide destroyed the village Ab Barek, a village in Badakshan Province, Afghanistan. The landslide caused several hundred fatalities and once again demonstrated the vulnerability of Afghanistan's population to extreme natural events following more than 30 years of civil war and violent conflict. Increasing the capacity of Afghanistan's population by strengthening the disaster preparedness and management of responsible government authorities and institutions is thus a major component of international cooperation and development strategies. Afghanistan is characterized by high relief and widely varying rock types that largely determine the spatial distribution as well as emplacement modes of mass movements. The major aim of our study is to characterize this variability by conducting a landslide susceptibility analysis in three selected target zones: Greater Kabul Area, Badakhshan Province and Takhar Province. We expand on an existing landslide database by mapping landforms diagnostic for landslides (e.g. head scarps, normal faults and tension cracks), and historical landslide scars and landslide deposits by visual interpretation of high-resolution satellite imagery. We conduct magnitude frequency analysis within subregional physiogeographic classes based on geological maps, climatological and topographic data to identify regional parameters influencing landslide magnitude and frequency. In addition, we prepare a landslide susceptibility map for each area using the Weight-of-Evidence model. Preliminary results show that the three selected target zones vastly differ in modes of landsliding. Low magnitude but frequent rockfall events are a major hazard in the Greater Kabul Area threatening buildings and infrastructure encroaching steep terrain in the city's outskirts. Mass movements in loess covered areas of Badakshan are characterized by medium to large magnitudes. This spatial variability of characteristic landslide magnitudes and

  11. Automatic Target Recognition in Synthetic Aperture Sonar Images Based on Geometrical Feature Extraction

    Directory of Open Access Journals (Sweden)

    J. Del Rio Vera

    2009-01-01

    Full Text Available This paper presents a new supervised classification approach for automated target recognition (ATR in SAS images. The recognition procedure starts with a novel segmentation stage based on the Hilbert transform. A number of geometrical features are then extracted and used to classify observed objects against a previously compiled database of target and non-target features. The proposed approach has been tested on a set of 1528 simulated images created by the NURC SIGMAS sonar model, achieving up to 95% classification accuracy.

  12. Morphological neural networks for automatic target detection by simulated annealing learning algorithm

    Institute of Scientific and Technical Information of China (English)

    余农; 吴昊; 吴常泳; 李范鸣; 吴立德

    2003-01-01

    A practical neural network model for morphological filtering and a simulated annealing optimal algorithm for the network parameters training are proposed in this paper. It is pointed out that the optimal designing process of the morphological filtering network in fact is the optimal learning process of adjusting network parameters (structuring element, or SE for short) to accommodate image environment. Then the network structure may possess the characteristics ofimage targets, and so give specific infor- mation to the SE. Morphological filters formed in this way become certainly intelligent and can provide good filtering results and robust adaptability to complex changing image. For application tomotional image target detection, dynamic training algorithm is applied to the designing process using asymptotic shrinking error and appropriate network weights adjusting. Experimental results show that the algorithm has invariant propertywith respect to shift, scale and rotation of moving target in continuing detection of moving targets.

  13. Mitochondrial genomes are retained by selective constraints on protein targeting.

    Science.gov (United States)

    Björkholm, Patrik; Harish, Ajith; Hagström, Erik; Ernst, Andreas M; Andersson, Siv G E

    2015-08-18

    Mitochondria are energy-producing organelles in eukaryotic cells considered to be of bacterial origin. The mitochondrial genome has evolved under selection for minimization of gene content, yet it is not known why not all mitochondrial genes have been transferred to the nuclear genome. Here, we predict that hydrophobic membrane proteins encoded by the mitochondrial genomes would be recognized by the signal recognition particle and targeted to the endoplasmic reticulum if they were nuclear-encoded and translated in the cytoplasm. Expression of the mitochondrially encoded proteins Cytochrome oxidase subunit 1, Apocytochrome b, and ATP synthase subunit 6 in the cytoplasm of HeLa cells confirms export to the endoplasmic reticulum. To examine the extent to which the mitochondrial proteome is driven by selective constraints within the eukaryotic cell, we investigated the occurrence of mitochondrial protein domains in bacteria and eukaryotes. The accessory protein domains of the oxidative phosphorylation system are unique to mitochondria, indicating the evolution of new protein folds. Most of the identified domains in the accessory proteins of the ribosome are also found in eukaryotic proteins of other functions and locations. Overall, one-third of the protein domains identified in mitochondrial proteins are only rarely found in bacteria. We conclude that the mitochondrial genome has been maintained to ensure the correct localization of highly hydrophobic membrane proteins. Taken together, the results suggest that selective constraints on the eukaryotic cell have played a major role in modulating the evolution of the mitochondrial genome and proteome. PMID:26195779

  14. Real-time tumor tracking: Automatic compensation of target motion using the Siemens 160 MLC

    International Nuclear Information System (INIS)

    Purpose: Advanced high quality radiation therapy techniques such as IMRT require an accurate delivery of precisely modulated radiation fields to the target volume. Interfractional and intrafractional motion of the patient's anatomy, however, may considerably deteriorate the accuracy of the delivered dose to the planned dose distributions. In order to compensate for these potential errors, a dynamic real-time capable MLC control system was designed. Methods: The newly developed adaptive MLC control system contains specialized algorithms which are capable of continuous optimization and correction of the aperture of the MLC according to the motion of the target volume during the dose delivery. The algorithms calculate the new leaf positions based on target information provided online to the system. The algorithms were implemented in a dynamic target tracking control system designed for a Siemens 160 MLC. To assess the quality of the new target tracking system in terms of dosimetric accuracy, experiments with various types of motion patterns using different phantom setups were performed. The phantoms were equipped with radiochromic films placed between solid water slabs. Dosimetric results of exemplary deliveries to moving targets with and without dynamic MLC tracking applied were compared in terms of the gamma criterion to the reference dose delivered to a static phantom. Results: Our measurements indicated that dose errors for clinically relevant two-dimensional target motion can be compensated by the new control system during the dose delivery of open fields. For a clinical IMRT dose distribution, the gamma success rate was increased from 19% to 77% using the new tracking system. Similar improvements were achieved for the delivery of a complete IMRT treatment fraction to a moving lung phantom. However, dosimetric accuracy was limited by the system's latency of 400 ms and the finite leaf width of 5 mm in the isocenter plane. Conclusions: Different experimental setups

  15. Utilization of OIM for Measurement Selection in Multistatic Target Tracking

    Directory of Open Access Journals (Sweden)

    G. Soysal

    2014-04-01

    Full Text Available The sensor management problem can be expressed as obtaining the state estimation with desired accuracy by utilizing the resources effectively. In the literature, there are two principal approaches to this problem, namely task-driven and information driven sensor management. Performance metrics for both task-driven and information driven sensor management frameworks suffer from the heavy computational burden due to the evaluation of expectations or are available only in simulation. In this paper, the Observed Information Matrix (OIM, which is widely used in statistical practice as a surrogate for the Fisher Information Matrix (FIM in difficult problems, has been proposed as a metric that can be used in sensor management. Recursive computation of OIM has been derived for the cases with linear and nonlinear system dynamics corrupted with additive Gaussian noise. The usefulness of OIM in sensor selection in multistatic target tracking has been demonstrated via simulations.

  16. Cancer Immunotherapy: Selected Targets and Small-Molecule Modulators.

    Science.gov (United States)

    Weinmann, Hilmar

    2016-03-01

    There is a significant amount of excitement in the scientific community around cancer immunotherapy, as this approach has renewed hope for many cancer patients owing to some recent successes in the clinic. Currently available immuno-oncology therapeutics under clinical development and on the market are mostly biologics (antibodies, proteins, engineered cells, and oncolytic viruses). However, modulation of the immune system with small molecules offers several advantages that may be complementary and potentially synergistic to the use of large biologicals. Therefore, the discovery and development of novel small-molecule modulators is a rapidly growing research area for medicinal chemists working in cancer immunotherapy. This review provides a brief introduction into recent trends related to selected targets and pathways for cancer immunotherapy and their small-molecule pharmacological modulators. PMID:26836578

  17. Optimal landmarks selection and fiducial marker placement for minimal target registration error in image-guided neurosurgery

    Science.gov (United States)

    Shamir, Reuben R.; Joskowicz, Leo; Shoshan, Yigal

    2009-02-01

    We describe a new framework and method for the optimal selection of anatomical landmarks and optimal placement of fiducial markers in image-guided neurosurgery. The method allows the surgeon to optimally plan the markers locations on routine diagnostic images before preoperative imaging and to intraoperatively select the fiducial markers and the anatomical landmarks that minimize the Target Registration Error (TRE). The optimal fiducial marker configuration selection is performed by the surgeon on the diagnostic image following the target selection based on a visual Estimated TRE (E-TRE) map. The E-TRE map is automatically updated when the surgeon interactively adds and deletes candidate markers and targets. The method takes the guesswork out of the registration process, provides a reliable localization uncertainty error for navigation, and can reduce the localization error without additional imaging and hardware. Our clinical experiments on five patients who underwent brain surgery with a navigation system show that optimizing one marker location and the anatomical landmarks configuration reduces the average TRE from 4.7mm to 3.2mm, with a maximum improvement of 4mm. The reduction of the target registration error has the potential to support safer and more accurate minimally invasive neurosurgical procedures.

  18. CD133, Selectively Targeting the Root of Cancer

    Directory of Open Access Journals (Sweden)

    Jörg U. Schmohl

    2016-05-01

    Full Text Available Cancer stem cells (CSC are capable of promoting tumor initiation and self-renewal, two important hallmarks of carcinoma formation. This population comprises a small percentage of the tumor mass and is highly resistant to chemotherapy, causing the most difficult problem in the field of cancer research, drug refractory relapse. Many CSC markers have been reported. One of the most promising and perhaps least ubiquitous is CD133, a membrane-bound pentaspan glycoprotein that is frequently expressed on CSC. There is evidence that directly targeting CD133 with biological drugs might be the most effective way to eliminate CSC. We have investigated two entirely unrelated, but highly effective approaches for selectively targeting CD133. The first involves using a special anti-CD133 single chain variable fragment (scFv to deliver a catalytic toxin. The second utilizes this same scFv to deliver components of the immune system. In this review, we discuss the development and current status of these CD133 associated biological agents. Together, they show exceptional promise by specific and efficient CSC elimination.

  19. Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target.

    Science.gov (United States)

    Mazzone, P; Arena, P; Cantelli, L; Spampinato, G; Sposato, S; Cozzolino, S; Demarinis, P; Muscato, G

    2016-07-01

    The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery. PMID:27194228

  20. Stereographic Targeting in Prostate Radiotherapy: Speed and Precision by Daily Automatic Positioning Corrections Using Kilovoltage/Megavoltage Image Pairs

    International Nuclear Information System (INIS)

    Purpose: A fully automated, fast, on-line prostate repositioning scheme using implanted markers, kilovoltage/megavoltage imaging, and remote couch movements has been developed and clinically applied. The initial clinical results of this stereographic targeting (SGT) method, as well as phantom evaluations, are presented. Methods and Materials: Using the SGT method, portal megavoltage images are acquired with the first two to six monitor units of a treatment beam, immediately followed by acquisition of an orthogonal kilovoltage image without gantry motion. The image pair is automatically analyzed to obtain the marker positions and three-dimensional prostate displacement and rotation. Remote control couch shifts are applied to correct for the displacement. The SGT performance was measured using both phantom images and images from 10 prostate cancer patients treated using SGT. Results: With phantom measurements, the accuracy of SGT was 0.5, 0.2, and 0.3 mm (standard deviation [SD]) for the left-right, craniocaudal, and anteroposterior directions, respectively, for translations and 0.5o (SD) for the rotations around all axes. Clinically, the success rate for automatic marker detection was 99.5%, and the accuracy was 0.3, 0.5 and 0.8 mm (SD) in the left-right, craniocaudal, and anteroposterior axes. The SDs of the systematic center-of-mass positioning errors (Σ) were reduced from 4.0 mm to <0.5 mm for all axes. The corresponding SD of the random (σ) errors was reduced from 3.0 to <0.8 mm. These small residual errors were achieved with a treatment time extension of <1 min. Conclusion: Stereographic targeting yields systematic and random prostate positioning errors of <1 mm with <1 min of added treatment time

  1. A wearable ECG-HR detector and its application to automatic assist-mode selection of an electrically assisted bicycle.

    Science.gov (United States)

    Ueno, Akinori; Miyashita, Osamu; Yoshida, Toshiya; Yamamoto, Junichi; Lataire, Philippe

    2011-01-01

    Recently, an electrically assisted bicycle has been widely used in daily life and becomes very popular. The user selects the stepwise assist-mode to determine the assistive torque for pleasurable running. From the viewpoint of improvement of health by exercise, the electrically assisted bicycle can be an exercise machine like a treadmill. The heart rate (HR) is regarded as an indication of exercise load. This paper presents an automatic assist-mode selection system based on the HR of the bicycle user. The HR is obtained from the R-waves measured by the proposed wearable electrocardiograph on the user. The mode-selection system is simply implemented by a personal computer, USB-connected interface, and some electronic switching circuits. The running experiments confirm that the proposed assist-mode selection method has practicability. PMID:22255925

  2. The LEGUE disk target selection for the LAMOST pilot survey

    CERN Document Server

    Chen, Li; Yu, Jincheng; Liu, Chao; Deng, Licai; Newberg, Heidi Jo; Carlin, Jeffrey L; Yang, Fan; Zhang, Yueyang; Shen, Shiyin; Zhang, Haotong; Chen, Jianjun; Chen, Yuqing; Christlieb, Norbert; Han, Zhanwen; Lee, Hsu-Tai; Liu, Xiaowei; Pan, Kaike; Shi, Jianrong; Wang, Hongchi; Zhu, Zi

    2012-01-01

    We describe the target selection algorithm for the low latitude disk portion of the LAMOST Pilot Survey, which aims to test systems in preparation for the LAMOST spectroscopic survey. We use the PPMXL (Roeser et al. 2010) astrometric catalog, which provides positions, proper motions, B/R/I magnitudes (mostly) from USNO-B (Monet et al. 2003) and J/H/Ks from The Two Micron All Sky Survey (2MASS, see Skrutskie et al. 2006) as well. We chose 8 plates along the Galactic plane, in the region $0^\\circ<\\alpha<67^\\circ$ and $42^\\circ<\\delta<59^\\circ$, that cover 22 known open clusters with a range of ages. Adjacent plates may have small overlapping. Each plate covers an area $2.5^\\circ$ in radius,with central star (for Shark-Hartmann guider) brighter than $\\sim8^{\\rm th}$ magnitude. For each plate, we create an input catalog in the magnitude range $11.3selected to satisfy the requirements of the fiber positioning system and have a uniform dis...

  3. Iaser gun automatic shoting target and reporting%激光枪自动射击报靶装置

    Institute of Scientific and Technical Information of China (English)

    陈启昂; 潘瑶麟; 楼奇力

    2013-01-01

    This article is an automatic shooting indication of shots device design, largely by the Laser Gun and aiming, chest round target, correction detection circuit that some parts.The entire system is to control the k60 microcontroller core, through the camera, on the chest round target for image acquisition, processing, feedback to the SCM, determine where the correction, and can use the keyboard to change the wave pwm servo motor turns the appropriate angle, thus controlling laser correction.In addition to basic requirements met, the system designed to expand links : graphic dot matrix displays on the monitor chest round target graphics, and flash display correction.Automatic control of laser guns, the laser beam spot in 15 seconds from the rapid aiming at the specified location on the chest round target and hit the bull’s -eye ( that is, 10 Loop area ), other : Any number to ring, laser pointer to the appropriate place, is quite precise, and be able to voice indication of shots.%  本文设计的是一个自动射击报靶装置,主要由激光枪及瞄准机构、胸环靶、弹着点检测电路这几个部分构成。整个系统是以K60单片机为控制核心,通过摄像头,对胸环靶进行图像采集、处理,反馈给单片机,判断出弹着点所在位置,并且能通过键盘来改变PWM波使伺服电机转动相应角度,从而调控激光枪的弹着点。除基本要求满足外,本系统设计了一些拓展环节:图形点阵显示器上显示胸环靶的相应图形,并闪烁显示弹着点。自动控制激光枪,在15秒内将激光束光斑从胸环靶上的指定位置迅速瞄准并击中靶心(即10环区域),其他:任意给环数,激光笔打到相应位置,相当精确,并且能够语音报靶。

  4. AUTOMATIC MODEL SELECTION FOR 3D RECONSTRUCTION OF BUILDINGS FROM SATELLITE IMAGARY

    OpenAIRE

    T. Partovi; H. Arefi; T. Krauß; P. Reinartz

    2013-01-01

    Through the improvements of satellite sensor and matching technology, the derivation of 3D models from space borne stereo data obtained a lot of interest for various applications such as mobile navigation, urban planning, telecommunication, and tourism. The automatic reconstruction of 3D building models from space borne point cloud data is still an active research topic. The challenging problem in this field is the relatively low quality of the Digital Surface Model (DSM) generated by stereo ...

  5. AUTOMATIC MODEL SELECTION FOR 3D RECONSTRUCTION OF BUILDINGS FROM SATELLITE IMAGARY

    OpenAIRE

    T. Partovi; H. Arefi; T. Krauß; P. Reinartz

    2013-01-01

    Through the improvements of satellite sensor and matching technology, the derivation of 3D models from space borne stereo data obtained a lot of interest for various applications such as mobile navigation, urban planning, telecommunication, and tourism. The automatic reconstruction of 3D building models from space borne point cloud data is still an active research topic. The challenging problem in this field is the relatively low quality of the Digital Surface Model (DSM) generated by st...

  6. Defect Detection in Textures through the Use of Entropy as a Means for Automatically Selecting the Wavelet Decomposition Level.

    Science.gov (United States)

    Navarro, Pedro J; Fernández-Isla, Carlos; Alcover, Pedro María; Suardíaz, Juan

    2016-01-01

    This paper presents a robust method for defect detection in textures, entropy-based automatic selection of the wavelet decomposition level (EADL), based on a wavelet reconstruction scheme, for detecting defects in a wide variety of structural and statistical textures. Two main features are presented. One of the new features is an original use of the normalized absolute function value (NABS) calculated from the wavelet coefficients derived at various different decomposition levels in order to identify textures where the defect can be isolated by eliminating the texture pattern in the first decomposition level. The second is the use of Shannon's entropy, calculated over detail subimages, for automatic selection of the band for image reconstruction, which, unlike other techniques, such as those based on the co-occurrence matrix or on energy calculation, provides a lower decomposition level, thus avoiding excessive degradation of the image, allowing a more accurate defect segmentation. A metric analysis of the results of the proposed method with nine different thresholding algorithms determined that selecting the appropriate thresholding method is important to achieve optimum performance in defect detection. As a consequence, several different thresholding algorithms depending on the type of texture are proposed. PMID:27472343

  7. Using Fuzzy Modifier in Similarity Measure of Fuzzy Attribute Graph and Its Automatic Selection in Structural Pattern Recognition

    Directory of Open Access Journals (Sweden)

    Payman Moallem

    2007-09-01

    Full Text Available Fuzzy Attribute Graph (FAG is a powerful tool for representation and recognition of structural patterns. The conventional framework for similarity measure of FAGs is based on equivalent fuzzy attributes but in fuzzy world, some attributes are more important. In this paper, a modified recognition framework, using linguistic modifier for matching of the fuzzy attribute graphs, is introduced. Then an algorithm for automatic selection of fuzzy modifier based on the learning patterns is posed. Some examples for the conventional and modified framework for FAG similarity measure are studied and the potential of the proposed framework for FAG matching is showed.

  8. Human hair follicle: reservoir function and selective targeting.

    Science.gov (United States)

    Blume-Peytavi, U; Vogt, A

    2011-10-01

    Penetration of topically applied compounds may occur via the stratum corneum, skin appendages and hair follicles. The follicular infundibulum increases the surface area, disrupts the epidermal barrier towards the lower parts of the follicle, and serves as a reservoir. Topical delivery of active compounds to specific targets within the skin, especially to distinct hair follicle compartments or cell populations, may help to treat local inflammatory reactions selectively, with reduced systemic side-effects. Various in vitro and in vivo methods exist for studying the hair follicle structure and follicular penetration pathways. These include cyanoacrylate skin surface stripping, confocal microscopy and cyanoacrylate scalp follicle biopsy. The complex anatomical structure as well as the cyclical activity of the hair follicle must be taken into consideration when designing delivery systems. In addition, delivery into and retention inside the infundibular reservoir are controlled by, for example, molecule or particle size, their polarity and the type of preparation. Preferred penetration depth and storage time must also be considered. Particles with release mechanisms should be preferred; however, the release of drugs from nanoparticles still requires further investigations. PMID:21919898

  9. Effects of Mode of Target Task Selection on Learning about Plants in a Mobile Learning Environment: Effortful Manual Selection versus Effortless QR-Code Selection

    Science.gov (United States)

    Gao, Yuan; Liu, Tzu-Chien; Paas, Fred

    2016-01-01

    This study compared the effects of effortless selection of target plants using quick respond (QR) code technology to effortful manual search and selection of target plants on learning about plants in a mobile device supported learning environment. In addition, it was investigated whether the effectiveness of the 2 selection methods was…

  10. AUTOMATIC WEB SERVICE SELECTION BY OPTIMIZING COST OF COMPOSITION IN SLAKY COMPOSER USING ASSIGNMENT MINIMIZATION APPROACH

    Directory of Open Access Journals (Sweden)

    P. Sandhya

    2012-12-01

    Full Text Available Web service composition is a means of building enterprises virtually by knitting relevant web services on the fly. Automatic web service composition is done dynamically at runtime. Extensive research has been done in the field of automatic web service composition. However all the works focus on providing client oriented results and hence there is less industry adoption of composition technology. In this paper we have proposed a new service collaboration stack that composes with realistic business metrics of a provider in addition to client metrics. Some of the service provider metrics include time planning, profit management, native intelligence, user adoption, environment, market scenario, vision and industry adoption. In this paper we focus on enhancing industry adoption through optimizing cost of service composition. We propose the SLAKY composer that solves assignment of appropriate service during composition as an assignment minimization problem to reduce the cost of composition. We also extend OWL-S profile sub ontology to augment cost as a service parameter.

  11. Automatic detection of small bowel tumors in endoscopic capsule images by ROI selection based on discarded lightness information.

    Science.gov (United States)

    Vieira, Pedro M; Ramos, Jaime; Lima, Carlos S

    2015-08-01

    This paper addresses the problem of automatic detection of tumoral frames in endoscopic capsule videos by using features directly extracted from the color space. We show that tumor can be appropriately discriminated from normal tissue by using only color information histogram measures from the Lab color space and that light saturated regions are usually classified as tumoral regions when color based discriminative procedures are used. These regions are correctly classified if lightening is discarded becoming the tissue classifier based only on the color differences a and b of the Lab color space. While current state of the art systems for small bowel tumor detection usually rely on the processing of the whole frame regarding features extraction this paper proposes the use of fully automatic segmentation in order to select regions likely to contain tumoral tissue. Classification is performed by using Support Vector Machine (SVM) and Multilayer Perceptron (MLP) by using features from color channels a and b of the Lab color space. The proposed algorithm outperforms in more than 5% a series of other algorithms based on features obtained from the higher frequency components selected from Wavelets and Curvelets transforms while saving important computational resources. In a matter of fact the proposed algorithm is more than 25 times faster than algorithms requiring wavelet/curvelet and co-occurrence computations. PMID:26736929

  12. Performance portability study of an automatic target detection and classification algorithm for hyperspectral image analysis using OpenCL

    Science.gov (United States)

    Bernabe, Sergio; Igual, Francisco D.; Botella, Guillermo; Garcia, Carlos; Prieto-Matias, Manuel; Plaza, Antonio

    2015-10-01

    Recent advances in heterogeneous high performance computing (HPC) have opened new avenues for demanding remote sensing applications. Perhaps one of the most popular algorithm in target detection and identification is the automatic target detection and classification algorithm (ATDCA) widely used in the hyperspectral image analysis community. Previous research has already investigated the mapping of ATDCA on graphics processing units (GPUs) and field programmable gate arrays (FPGAs), showing impressive speedup factors that allow its exploitation in time-critical scenarios. Based on these studies, our work explores the performance portability of a tuned OpenCL implementation across a range of processing devices including multicore processors, GPUs and other accelerators. This approach differs from previous papers, which focused on achieving the optimal performance on each platform. Here, we are more interested in the following issues: (1) evaluating if a single code written in OpenCL allows us to achieve acceptable performance across all of them, and (2) assessing the gap between our portable OpenCL code and those hand-tuned versions previously investigated. Our study includes the analysis of different tuning techniques that expose data parallelism as well as enable an efficient exploitation of the complex memory hierarchies found in these new heterogeneous devices. Experiments have been conducted using hyperspectral data sets collected by NASA's Airborne Visible Infra- red Imaging Spectrometer (AVIRIS) and the Hyperspectral Digital Imagery Collection Experiment (HYDICE) sensors. To the best of our knowledge, this kind of analysis has not been previously conducted in the hyperspectral imaging processing literature, and in our opinion it is very important in order to really calibrate the possibility of using heterogeneous platforms for efficient hyperspectral imaging processing in real remote sensing missions.

  13. Phobias and preparedness: the selective, automatic, and encapsulated nature of fear.

    Science.gov (United States)

    Mineka, Susan; Ohman, Arne

    2002-11-15

    We describe evidence for an evolved module for fear elicitation and fear learning with four primary characteristics. First, it is preferentially activated by stimuli related to survival threats in evolutionary history. Thus, fear-relevant stimuli lead to superior conditioning of aversive associations compared with fear-irrelevant stimuli. Second, the module is automatically activated by fear-relevant stimuli, meaning that fear activation occurs before conscious cognitive analysis of the stimulus can occur. Third, the fear module is relatively impenetrable to conscious cognitive control, and fear conditioning with fear-relevant stimuli can occur even with subliminal conditioned stimuli. Fourth, the amygdala seems to be the central brain area dedicated to the fear module. Finally, we propose that there are two levels of fear conditioning, with an emotional level that is relatively independent of the cognitive contingency level, each mediated by different brain areas. PMID:12437934

  14. 自动灭火系统的选择与应用技术探讨%Selection and application technology of automatic fire extinguishing system

    Institute of Scientific and Technical Information of China (English)

    李云浩; 黄晓家; 张兆宪

    2011-01-01

    The selection of automatic fire extinguishing system has been gradually released in national codes. The selection and application of automatic fire extinguishing system has become the focus of fire engineering design. Based on codes, the mechanism , performance and adaptability of automatic fire extinguishing system are listed. Impact factors and selection principles of system selection have been proposed to provide the basis for the fire engineering design.%我国规范对于自动灭火系统的选择逐步放开,自动灭火系统的选择和应用已成为消防工程设计的重点.从规范出发,给出自动灭火系统的灭火机理、性能和适应性以及系统选择影响因子和选择原则,为消防工程设计提供依据.

  15. Evaluation of the accuracy of different combinations of automatic registration selection factors in obtaining tomotherapy megavoltage computed tomography images

    International Nuclear Information System (INIS)

    The purpose of our study is to find the potential best options for the registration selection parameters when performing automatic registration between kilovoltage computed tomography (KVCT) and megavoltage computed tomography (MVCT) images in helical tomotherapy. We compared nine different combinations of automatic registration parameters, including technique and resolution in automatic registration control and tomoimage filtering in scan image control. In the phantom study, we compared the translational and the rotational adjustments between the original position (lateral 0 cm; longitudinal 0 cm; vertical 0 cm) and the manually moved position (lateral 1 cm; longitudinal 1 cm; vertical 1 cm). In the patient study, we compared translational (lateral, longitudinal, vertical) and rotational (pitch, roll, yaw) adjustments between the KVCT and the MVCT images for different anatomic treatment sites. The ranges of translational and rotational displacements in the phantom study were 14.87 ± 0.12 ∼ 15.70 ± 0.04 mm and 0 .deg. ∼ 1.03 ± 0.58 .deg. , respectively. In cranial cases, the ranges of translational and rotational root-mean-square values were 4.3 ± 0.4 mm ∼ 5.3 ± 0.6 mm, and 0.3 ± 0.3 .deg. ∼ 0.7 ± 0.4 .deg. , respectively. In the extra cranial cases, the ranges of translational and rotational root-mean-square values were 14.1 ± 3.6 mm ∼ 16.1 ± 2.5 mm, and 0.5 ± 0.3 .deg. ∼ 1.0 ± 0.5 .deg. , respectively. We found that the combination of 'full image - super fine' could minimize the mechanical deviations in the cranial case, and that both the combinations of 'bone tissue - super fine' and 'full image - super fine' were the best options in extra cranial cases.

  16. MLENN-KELM: a Prototype Selection Based Kernel Extreme Learning Machine Approach for Large-Scale Automatic Image Annotation

    Directory of Open Access Journals (Sweden)

    Hamid Kargar-Shooroki

    2015-09-01

    Full Text Available With the fast growth of digital images in web, large-scale Automatic Image Annotation (AIA dealt with some of critical challenges. The most important of them are system scalability and annotation performance. On the other hand, learning methods in the large-scale systems with the large number of training instances cannot correctly perform and deal with memory and learning time restrictions. In this paper in order to solve the performance of large-scale AIA systems, and limitations of employing learning methods in these systems, MLENN-KELM approach has been proposed. In the proposed approach, first, most effective instances are selected from training set by Prototype Selection (PS methods. The basic assumption of selecting effective instances is reducing the size of training set and solving memory restrictions in large-scale AIA systems and learning methods. Then, annotation process is done by Kernel Extreme Learning Machine algorithm (KELM. The main advantage of using KELM algorithm is the improvement of annotation performance than other learning methods. Experimental results on NUS-WIDE-Object image set demonstrate the good performance of proposed approach in solving large-scale AIA challenges and also capability improvement of KELM algorithm in large-scale applications.

  17. Targeting extracellular pyrophosphates underpins the high selectivity of nisin.

    Science.gov (United States)

    Bonev, Boyan B; Breukink, Eefjan; Swiezewska, E; De Kruijff, Ben; Watts, Anthony

    2004-12-01

    The spread of infectious diseases and the increase in antibiotic resistance represent a life-threatening global development that calls for new approaches to control microorganisms. Of all potential targets, the essential and unique pathway of bacterial cell wall synthesis, targeted by the first known antibiotic penicillin, remains a perfect candidate for the development of new antibiotics. Here we show that the lantibiotic nisin exercises its antibacterial action by targeting peptidoglycan intermediates' extracellular pyrophosphate, unique to bacterial cell wall precursors. We show that nisin sequesters cell wall precursors found in the outer leaflet of bacterial plasma membranes, Lipid II and undecaprenyl pyrophosphate, into stable complexes. We propose a model of antibacterial action for nisin in which the terminal amino group of Ile1 targets the pyrophosphate groups of the bacterial cell wall precursors, where it docks via a hydrogen bond. The pyrophosphate moiety, a highly conserved chemical group different from the L-Lys-D-Ala-D-Ala docking motif for vancomycin, has no biochemical analogs with comparable properties and is unlikely to be susceptible to bacterial adaptations akin to those responsible for resistance to penicillins and vancomycin. PMID:15576489

  18. Involvement of Tspan8 in exosome assembly and target cell selection

    OpenAIRE

    Rana, Sanyukta

    2010-01-01

    Exosomes are the most important intercellular communicators. Tetraspanins/their complexes are suggested to be important in exosomal target cell selection. I showed: changes in Tetraspanin8 associations created from internalization persist upto exosomes and, differences in tetraspanin-complexes on exosomes allow for target cell selectivity.Based on the tetraspanin-complex on exosomes, predictions on potential target cells might be possible, allowing tailored exosome generation for drug delivery.

  19. The safety of ONRAB® in select non-target wildlife.

    Science.gov (United States)

    Fry, Tricia L; Vandalen, Kaci K; Duncan, Colleen; Vercauteren, Kurt

    2013-08-20

    ONRAB(®) is a recombinant human adenovirus type 5 (HAd5) with the rabies glycoprotein gene incorporated into its genome. ONRAB(®) has been used in Canada as an oral rabies vaccine in target wildlife species such as: red fox (Vulpes vulpes), raccoon (Procyon lotor), and striped skunk (Mepthis mephitis). We evaluated the safety of ONRAB(®) in non-target wildlife species likely to contact the vaccine baits during oral rabies vaccine campaigns in the United States. We investigated the effects of oral inoculation of high titer ONRAB(®), approximately ten times the dose given to target species, in wood rats (Neotoma spp.), eastern cottontail rabbits (Sylvilagus floridanus), Virginia opossums (Didelphis virginiana), eastern wild turkeys (Meleagris gallopavo silvestri), and fox squirrels (Sciurus niger). We performed real-time polymerase chain reaction (PCR) on fecal swabs, oral swabs, and tissues, including lung, liver, kidney, small intestine, large intestine, and when appropriate nasal turbinates, to detect ONRAB(®) DNA from inoculated animals. By seven days post-inoculation, turkeys, opossums, and cottontails had all stopped shedding ONRAB(®) DNA. One wood rat and one fox squirrel still had detectable levels of ONRAB(®) DNA in fecal swabs 14 days post-inoculation. Real-time PCR analysis of the tissues revealed some ONRAB(®) DNA persisting in certain tissues; however, there were no significant gross or histologic lesions associated with ONRAB(®) in any of the species studied. Our results suggest that many non-target species are not likely to be impacted by the distribution of ONRAB(®) as part of oral rabies vaccination programs in the United States. PMID:23831321

  20. Signal Transduction and Molecular Targets of Selected Flavonoids

    OpenAIRE

    Bode, Ann M.; Dong, Zigang

    2013-01-01

    Significance: Diet exerts a major influence on the risk for developing cancer and heart disease. Food factors such as flavonoids are alleged to protect cells from premature aging and disease by shielding DNA, proteins, and lipids from oxidative damage. Recent Advances: Our work has focused on clarifying the effects of dietary components on cancer cell proliferation and tumor growth, discovering mechanisms to explain the effects, and identifying the specific molecular targets of these compound...

  1. Rational design of chemical ligands for selective mitochondrial targeting

    Czech Academy of Sciences Publication Activity Database

    Rimpelová, S.; Bříza, T.; Králová, Jarmila; Záruba, K.; Kejík, Z.; Císařová, I.; Martásek, P.; Ruml, T.; Král, V.

    2013-01-01

    Roč. 24, č. 9 (2013), s. 1445-1454. ISSN 1520-4812 R&D Projects: GA ČR(CZ) GAP303/11/1291; GA ČR GA203/09/1311 Grant ostatní: GA AV ČR(CZ) KAN200100801; GA MŠk(CZ) ED0030/01/01 Institutional support: RVO:68378050 Keywords : intracellular targeting * mitochondria * cardiolipin * pentamethine * fluorescent dyes Subject RIV: EB - Genetics ; Molecular Biology

  2. Target selection by natural and redesigned PUF proteins.

    Science.gov (United States)

    Porter, Douglas F; Koh, Yvonne Y; VanVeller, Brett; Raines, Ronald T; Wickens, Marvin

    2015-12-29

    Pumilio/fem-3 mRNA binding factor (PUF) proteins bind RNA with sequence specificity and modularity, and have become exemplary scaffolds in the reengineering of new RNA specificities. Here, we report the in vivo RNA binding sites of wild-type (WT) and reengineered forms of the PUF protein Saccharomyces cerevisiae Puf2p across the transcriptome. Puf2p defines an ancient protein family present throughout fungi, with divergent and distinctive PUF RNA binding domains, RNA-recognition motifs (RRMs), and prion regions. We identify sites in RNA bound to Puf2p in vivo by using two forms of UV cross-linking followed by immunopurification. The protein specifically binds more than 1,000 mRNAs, which contain multiple iterations of UAAU-binding elements. Regions outside the PUF domain, including the RRM, enhance discrimination among targets. Compensatory mutants reveal that one Puf2p molecule binds one UAAU sequence, and align the protein with the RNA site. Based on this architecture, we redesign Puf2p to bind UAAG and identify the targets of this reengineered PUF in vivo. The mutant protein finds its target site in 1,800 RNAs and yields a novel RNA network with a dramatic redistribution of binding elements. The mutant protein exhibits even greater RNA specificity than wild type. The redesigned protein decreases the abundance of RNAs in its redesigned network. These results suggest that reengineering using the PUF scaffold redirects and can even enhance specificity in vivo. PMID:26668354

  3. Automatic selection of reference taxa for protein-protein interaction prediction with phylogenetic profiling

    DEFF Research Database (Denmark)

    Simonsen, Martin; Maetschke, S.R.; Ragan, M.A.

    2012-01-01

    Motivation: Phylogenetic profiling methods can achieve good accuracy in predicting protein–protein interactions, especially in prokaryotes. Recent studies have shown that the choice of reference taxa (RT) is critical for accurate prediction, but with more than 2500 fully sequenced taxa publicly......: We present three novel methods for automating the selection of RT, using machine learning based on known protein–protein interaction networks. One of these methods in particular, Tree-Based Search, yields greatly improved prediction accuracies. We further show that different methods for constituting...

  4. Leveraging Big Data to Transform Target Selection and Drug Discovery

    Science.gov (United States)

    Chen, B; Butte, AJ

    2016-01-01

    The advances of genomics, sequencing, and high throughput technologies have led to the creation of large volumes of diverse datasets for drug discovery. Analyzing these datasets to better understand disease and discover new drugs is becoming more common. Recent open data initiatives in basic and clinical research have dramatically increased the types of data available to the public. The past few years have witnessed successful use of big data in many sectors across the whole drug discovery pipeline. In this review, we will highlight the state of the art in leveraging big data to identify new targets, drug indications, and drug response biomarkers in this era of precision medicine. PMID:26659699

  5. Selection or Influence? Institutional Investors and Acquisition Targets

    OpenAIRE

    Qiu, Lily; WAN, HONG

    2006-01-01

    This paper shows that the positive correlation between the presence of institutional investors and a firm’s likelihood of being acquired is due to ownership endogeneity, i.e., due to the fact that institutions are better informed investors. After controlling for this ownership endogeneity, the presence of institutional investors reduces the probability of being acquired. There is also evidence that mutual funds or funds with high turnover rates are more likely to benefit from selective disclo...

  6. A Fast Global Node Selection Algorithm for Bearings-only Target Localization

    Institute of Scientific and Technical Information of China (English)

    Rui Liyang; Xu Zhen

    2008-01-01

    In the target tracking, the nodes aggregate their observations of the directions of arrival of the target. The network then uses an extended Kalman filter (EKF) to combine the measurements from multiple snapshots to track the target. In order to rapidly select the best subset of nodes to localize the target with the minimum mean square position error and low power consumption, this paper proposes a simple algorithm, which uses the location information of the target and the network. The lower bound of localization error is utilized according to the distances between the target and the selected active nodes. Furthermore, the direction likelihoods of the active nodes is predicted by way of the node/target bearing distributing relationships.

  7. Quantitative modeling of selective lysosomal targeting for drug design

    DEFF Research Database (Denmark)

    Trapp, Stefan; Rosania, G.; Horobin, R.W.;

    2008-01-01

    Lysosomes are acidic organelles and are involved in various diseases, the most prominent is malaria. Accumulation of molecules in the cell by diffusion from the external solution into cytosol, lysosome and mitochondrium was calculated with the Fick–Nernst–Planck equation. The cell model considers...... the diffusion of neutral and ionic molecules across biomembranes, protonation to mono- or bivalent ions, adsorption to lipids, and electrical attraction or repulsion. Based on simulation results, high and selective accumulation in lysosomes was found for weak mono- and bivalent bases with intermediate...... to high log K ow. These findings were validated with experimental results and by a comparison to the properties of antimalarial drugs in clinical use. For ten active compounds, nine were predicted to accumulate to a greater extent in lysosomes than in other organelles, six of these were in the...

  8. Visual cells remember earlier applied target: plasticity of orientation selectivity.

    Directory of Open Access Journals (Sweden)

    Narcis Ghisovan

    Full Text Available BACKGROUND: A canonical proposition states that, in mature brain, neurons responsive to sensory stimuli are tuned to specific properties installed shortly after birth. It is amply demonstrated that that neurons in adult visual cortex of cats are orientation-selective that is they respond with the highest firing rates to preferred oriented stimuli. METHODOLOGY/PRINCIPAL FINDINGS: In anesthetized cats, prepared in a conventional fashion for single cell recordings, the present investigation shows that presenting a stimulus uninterruptedly at a non-preferred orientation for twelve minutes induces changes in orientation preference. Across all conditions orientation tuning curves were investigated using a trial by trial method. Contrary to what has been previously reported with shorter adaptation duration, twelve minutes of adaptation induces mostly attractive shifts, i.e. toward the adapter. After a recovery period allowing neurons to restore their original orientation tuning curves, we carried out a second adaptation which produced three major results: (1 more frequent attractive shifts, (2 an increase of their magnitude, and (3 an additional enhancement of responses at the new or acquired preferred orientation. Additionally, we also show that the direction of shifts depends on the duration of the adaptation: shorter adaptation in most cases produces repulsive shifts, whereas adaptation exceeding nine minutes results in attractive shifts, in the same unit. Consequently, shifts in preferred orientation depend on the duration of adaptation. CONCLUSION/SIGNIFICANCE: The supplementary response improvements indicate that neurons in area 17 keep a memory trace of the previous stimulus properties, thereby upgrading cellular performance. It also highlights the dynamic nature of basic neuronal properties in adult cortex since repeated adaptations modified both the orientation tuning selectivity and the response strength to the preferred orientation. These

  9. Some Results on the Target Set Selection Problem

    CERN Document Server

    Chiang, Chun-Ying; Li, Bo-Jr; Wu, Jiaojiao; Yeh, Hong-Gwa

    2011-01-01

    In this paper we consider a fundamental problem in the area of viral marketing, called T{\\scriptsize ARGET} S{\\scriptsize ET} S{\\scriptsize ELECTION} problem. We study the problem when the underlying graph is a block-cactus graph, a chordal graph or a Hamming graph. We show that if $G$ is a block-cactus graph, then the T{\\scriptsize ARGET} S{\\scriptsize ET} S{\\scriptsize ELECTION} problem can be solved in linear time, which generalizes Chen's result \\cite{chen2009} for trees, and the time complexity is much better than the algorithm in \\cite{treewidth} (for bounded treewidth graphs) when restricted to block-cactus graphs. We show that if the underlying graph $G$ is a chordal graph with thresholds $\\theta(v)\\leq 2$ for each vertex $v$ in $G$, then the problem can be solved in linear time. For a Hamming graph $G$ having thresholds $\\theta(v)=2$ for each vertex $v$ of $G$, we precisely determine an optimal target set $S$ for $(G,\\theta)$. These results partially answer an open problem raised by Dreyer and Robert...

  10. A swarm-trained k-nearest prototypes adaptive classifier with automatic feature selection for interval data.

    Science.gov (United States)

    Silva Filho, Telmo M; Souza, Renata M C R; Prudêncio, Ricardo B C

    2016-08-01

    Some complex data types are capable of modeling data variability and imprecision. These data types are studied in the symbolic data analysis field. One such data type is interval data, which represents ranges of values and is more versatile than classic point data for many domains. This paper proposes a new prototype-based classifier for interval data, trained by a swarm optimization method. Our work has two main contributions: a swarm method which is capable of performing both automatic selection of features and pruning of unused prototypes and a generalized weighted squared Euclidean distance for interval data. By discarding unnecessary features and prototypes, the proposed algorithm deals with typical limitations of prototype-based methods, such as the problem of prototype initialization. The proposed distance is useful for learning classes in interval datasets with different shapes, sizes and structures. When compared to other prototype-based methods, the proposed method achieves lower error rates in both synthetic and real interval datasets. PMID:27152933

  11. The use of automatic scale selection to improve the spatial and spectral resolution of a scintillator-coupled EMCCD

    International Nuclear Information System (INIS)

    The technology behind the Electron-Multiplying Charge Coupled Device (EMCCD) was successfully exploited by e2v technologies in the late 1990s. Since then, many uses have been found for these low light level (L3) devices including surveillance and many scientific applications. The EMCCD increases or 'multiplies' the charge signal by the phenomenon of impact ionisation (or avalanche multiplication) allowing the detection of low signal events of only a few photons. When coupled with a scintillator, this low light capability can be used to image photon flashes from individual X-ray interaction events. The combination of depth of interaction effects in the scintillator, shot noise on the signal and the multiplication noise factor lead to large variations in the profile of the detected signal from a constant energy X-ray source. This variation leads to reduced spectral performance and can have adverse effects on the centering techniques used in photon-counting imagers. The concept of scale-space is similar in many ways to the Fourier or wavelet transforms. Automatic scale selection can be implemented through the scale-space transform as a method of fitting a known profile to the observed photon flash. The process is examined here in the context of the photon-counting EMCCD detector and the results obtained in both simulated and experimental data compared. Through the analysis of the fitting process and the results achieved, the implications on imaging performance and spectral resolution are discussed.

  12. Gold nanorods for target selective SPECT/CT imaging and photothermal therapy in vivo

    OpenAIRE

    Jang, Boseung; Park, Seonhwa; Kang, Se Hun; Kim, Joa Kyum; Kim, Seok-Ki; Kim, In-Hoo; Choi, Yongdoo

    2012-01-01

    The development of theranostic agents with high detection sensitivity and antitumor efficacy at low concentration is a challenging task for target selective imaging and therapy of cancers. In this study, folate-conjugated and radioactive-iodine-labeled gold nanorods (GNRs) were designed and synthesized for target selective SPECT/CT imaging and subsequent thermal ablation of folate-receptor-overexpressing cancers. Both (ortho-pyridyl) disulfide-poly(ethylene glycol)-folate and a short peptide,...

  13. Chemical tools selectively target components of the PKA system

    Directory of Open Access Journals (Sweden)

    Drewianka Stephan

    2009-02-01

    Full Text Available Abstract Background In the eukaryotic cell the cAMP-dependent protein kinase (PKA is a key enzyme in signal transduction and represents the main target of the second messenger cAMP. Here we describe the design, synthesis and characterisation of specifically tailored cAMP analogs which can be utilised as a tool for affinity enrichment and purification as well as for proteomics based analyses of cAMP binding proteins. Results Two sets of chemical binders were developed based on the phosphorothioate derivatives of cAMP, Sp-cAMPS and Rp-cAMPS acting as cAMP-agonists and -antagonists, respectively. These compounds were tested via direct surface plasmon resonance (SPR analyses for their binding properties to PKA R-subunits and holoenzyme. Furthermore, these analogs were used in an affinity purification approach to analyse their binding and elution properties for the enrichment and improvement of cAMP binding proteins exemplified by the PKA R-subunits. As determined by SPR, all tested Sp-analogs provide valuable tools for affinity chromatography. However, Sp-8-AEA-cAMPS displayed (i superior enrichment properties while maintaining low unspecific binding to other proteins in crude cell lysates, (ii allowing mild elution conditions and (iii providing the capability to efficiently purify all four isoforms of active PKA R-subunit in milligram quantities within 8 h. In a chemical proteomics approach both sets of binders, Rp- and Sp-cAMPS derivatives, can be employed. Whereas Sp-8-AEA-cAMPS preferentially binds free R-subunit, Rp-AHDAA-cAMPS, displaying antagonist properties, not only binds to the free PKA R-subunits but also to the intact PKA holoenzyme both from recombinant and endogenous sources. Conclusion In summary, all tested cAMP analogs were useful for their respective application as an affinity reagent which can enhance purification of cAMP binding proteins. Sp-8-AEA-cAMPS was considered the most efficient analog since Sp-8-AHA-cAMPS and Sp-2-AHA

  14. Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes.

    OpenAIRE

    Groote, De, T.; Verschure, P.J.; Rots, M G

    2012-01-01

    Despite significant advances made in epigenetic research in recent decades, many questions remain unresolved, especially concerning cause and consequence of epigenetic marks with respect to gene expression modulation (GEM). Technologies allowing the targeting of epigenetic enzymes to predetermined DNA sequences are uniquely suited to answer such questions and could provide potent (bio)medical tools. Toward the goal of gene-specific GEM by overwriting epigenetic marks (Epigenetic Editing, EGE)...

  15. Epigenetic Editing: targeted rewriting of epigenetic marks to modulate expression of selected target genes

    OpenAIRE

    Groote, de, Robert; Verschure, P.J.; Rots, M.G.

    2012-01-01

    Despite significant advances made in epigenetic research in recent decades, many questions remain unresolved, especially concerning cause and consequence of epigenetic marks with respect to gene expression modulation (GEM). Technologies allowing the targeting of epigenetic enzymes to predetermined DNA sequences are uniquely suited to answer such questions and could provide potent (bio)medical tools. Toward the goal of gene-specific GEM by overwriting epigenetic marks (Epigenetic Editing, EGE)...

  16. Near Surface Swimming of Salmonella Typhimurium Explains Target-Site Selection and Cooperative Invasion

    OpenAIRE

    Misselwitz, Benjamin; Barrett, Naomi; Kreibich, Saskia; Vonaesch, Pascale; Andritschke, Daniel; Rout, Samuel; Weidner, Kerstin; Sormaz, Milos; Songhet, Pascal; Horvath, Peter; Chabria, Mamta; Vogel, Viola; Spori, Doris M.; Jenny, Patrick; Hardt, Wolf-Dietrich

    2012-01-01

    Targeting of permissive entry sites is crucial for bacterial infection. The targeting mechanisms are incompletely understood. We have analyzed target-site selection by S. Typhimurium. This enteropathogenic bacterium employs adhesins (e.g. fim) and the type III secretion system 1 (TTSS-1) for host cell binding, the triggering of ruffles and invasion. Typically, S. Typhimurium invasion is focused on a subset of cells and multiple bacteria invade via the same ruffle. It has remained unclear how ...

  17. Non-targeted evaluation of selectivity of water-compatible class selective adsorbents for the analysis of steroids in wastewater.

    Science.gov (United States)

    Kopperi, Matias; Riekkola, Marja-Liisa

    2016-05-12

    Selective adsorbents for solid-phase extraction are needed to meet the low concentration requirements of new environmental quality standard directives, especially for the analysis of estrogens in wastewater. In this work, bulk polymerization procedures were first optimized for the synthesis of non-imprinted polymers (NIP) with low non-specific adsorption of nonpolar compounds in aqueous environments. Water-compatible molecularly imprinted polymers (MIP) were then synthetized by increasing the selectivity of the polymer towards steroids with a testosterone template (average imprinting factor > 10). In addition, the affinity of synthetized entrapped β-cyclodextrin-epichlorohydrin polymers (ECD) towards steroids was clarified. The polymers were applied to the extraction of spiked wastewater effluent samples and their performance compared to commercially available adsorbents. The selectivity of the studied adsorbents was evaluated utilizing liquid chromatography ‒ mass spectrometry as well as comprehensive two-dimensional gas chromatography ‒ time-of-flight mass spectrometry. Affinity between adsorbents and steroids as well as matrix removal potential were measured with targeted methodologies, and two novel non-targeted methodologies were proposed to quantitatively measure adsorbent selectivity by utilizing chemometrics. Semi-quantitative selectivity was measured from the ratio of peak areas between steroidal and other compounds. Semi-qualitative selectivity was calculated from the ratio between the number of tentatively identified steroidal and other compounds. The synthetized polymers provided good matrix removal potential (ion suppression 15-30%) and semi-qualitative selectivity (∼4 units) compared to the commercial adsorbents (ion suppression 45-80%, selectivity < 3 units). Simple non-targeted approaches provided a novel method of quantifying the selectivity of extraction. PMID:27114222

  18. Influence of target concentration and background binding on in vitro selection of affinity reagents.

    Directory of Open Access Journals (Sweden)

    Jinpeng Wang

    Full Text Available Nucleic acid-based aptamers possess many useful features that make them a promising alternative to antibodies and other affinity reagents, including well-established chemical synthesis, reversible folding, thermal stability and low cost. However, the selection process typically used to generate aptamers (SELEX often requires significant resources and can fail to yield aptamers with sufficient affinity and specificity. A number of seminal theoretical models and numerical simulations have been reported in the literature offering insights into experimental factors that govern the effectiveness of the selection process. Though useful, these previous models have not considered the full spectrum of experimental factors or the potential impact of tuning these parameters at each round over the course of a multi-round selection process. We have developed an improved mathematical model to address this important question, and report that both target concentration and the degree of non-specific background binding are critical determinants of SELEX efficiency. Although smaller target concentrations should theoretically offer superior selection outcome, we show that the level of background binding dramatically affect the target concentration that will yield maximum enrichment at each round of selection. Thus, our model enables experimentalists to determine appropriate target concentrations as a means for protocol optimization. Finally, we perform a comparative analysis of two different selection methods over multiple rounds of selection, and show that methods with inherently lower background binding offer dramatic advantages in selection efficiency.

  19. Concept for On-Board Safe Landing Target Selection and Landing for the Mars 2020 Mission

    Science.gov (United States)

    Brugarolas, P.; Chen, A.; Johnson, A.; Casoliva, J.; Singh, G.; Stehura, A.; Way, D.; Dutta, S.

    2014-06-01

    We present a concept for a potential enhancement to Mars 2020 to enable landing on hazardous landing sites. It adds to MSL-EDL the capability to select and divert to a safe site through on-board terrain relative localization and target selection.

  20. Monitoring targeted therapy using dual-energy CT: semi-automatic RECIST plus supplementary functional information by quantifying iodine uptake of melanoma metastases

    Science.gov (United States)

    Sedlmair, M.; Schlemmer, H.P.; Hassel, J.C.; Ganten, M.

    2013-01-01

    Abstract Aim: Supplementary functional information can contribute to assess response in targeted therapies. The aim of this study was to evaluate semi-automatic RECIST plus iodine uptake (IU) determination in melanoma metastases under BRAF inhibitor (vemurafenib) therapy using dual-energy computed tomography (DECT). Methods: Nine patients with stage IV melanoma treated with a BRAF inhibitor were included. Contrast-enhanced DECT was performed before and twice after treatment onset. Changes in tumor size were assessed according to RECIST. Quantification of IU (absolute value for total IU (mg) and volume-normalized IU (mg/ml)) was based on semi-automatic tumor volume segmentation. The decrease compared with baseline was calculated. Results: The mean change of RECIST diameter sum per patient was −47% at the first follow-up (FU), −56% at the second FU (P < 0.01). The mean normalized IU per patient was −21% at the first FU (P < 0.2) and −45% at the second FU (P < 0.01). Total IU per patient, combining both normalized IU and volume, showed the most pronounced decrease: −89% at the first FU and −90% at the second FU (P < 0.01). Conclusion: Semi-automatic RECIST plus IU quantification in DECT enables objective, easy and fast parameterization of tumor size and contrast medium uptake, thus providing 2 complementary pieces of information for response monitoring applicable in daily routine. PMID:23876444

  1. Efficient conditional knockout targeting vector construction using co-selection BAC recombineering (CoSBR)

    OpenAIRE

    Robert J. Newman; Roose-Girma, Merone; Warming, Søren

    2015-01-01

    A simple and efficient strategy for Bacterial Artificial Chromosome (BAC) recombineering based on co-selection is described. We show that it is possible to efficiently modify two positions of a BAC simultaneously by co-transformation of a single-stranded DNA oligo and a double-stranded selection cassette. The use of co-selection BAC recombineering reduces the DNA manipulation needed to make a conditional knockout gene targeting vector to only two steps: a single round of BAC modification foll...

  2. Iterative reconstruction and individualized automatic tube current selection reduce radiation dose while maintaining image quality in 320-multidetector computed tomography coronary angiography

    International Nuclear Information System (INIS)

    Aim: To assess the effect of two iterative reconstruction algorithms (AIDR and AIDR3D) and individualized automatic tube current selection on radiation dose and image quality in computed tomography coronary angiography (CTCA). Materials and methods: In a single-centre cohort study, 942 patients underwent electrocardiogram-gated CTCA using a 320-multidetector CT system. Images from group 1 (n = 228) were reconstructed with a filtered back projection algorithm (Quantum Denoising Software, QDS+). Iterative reconstruction was used for group 2 (AIDR, n = 379) and group 3 (AIDR3D, n = 335). Tube current was selected based on body mass index (BMI) for groups 1 and 2, and selected automatically based on scout image attenuation for group 3. Subjective image quality was graded on a four-point scale (1 = excellent, 4 = non-diagnostic). Results: There were no differences in age (p = 0.975), body mass index (p = 0.435), or heart rate (p = 0.746) between the groups. Image quality improved with iterative reconstruction and automatic tube current selection [1.3 (95% confidence intervals (CI): 1.2–1.4), 1.2 (1.1–1.2) and 1.1 (1–1.2) respectively; p < 0.001] and radiation dose decreased [274 (260–290), 242 (230–253) and 168 (156–180) mGy cm, respectively; p < 0.001]. Conclusion: The application of the latest iterative reconstruction algorithm and individualized automatic tube current selection can substantially reduce radiation dose whilst improving image quality in CTCA

  3. A semantic approach to the efficient integration of interactive and automatic target recognition systems for the analysis of complex infrastructure from aerial imagery

    Science.gov (United States)

    Bauer, A.; Peinsipp-Byma, E.

    2008-04-01

    The analysis of complex infrastructure from aerial imagery, for instance a detailed analysis of an airfield, requires the interpreter, besides to be familiar with the sensor's imaging characteristics, to have a detailed understanding of the infrastructure domain. The required domain knowledge includes knowledge about the processes and functions involved in the operation of the infrastructure, the potential objects used to provide those functions and their spatial and functional interrelations. Since it is not possible yet to provide reliable automatic object recognition (AOR) for the analysis of such complex scenes, we developed systems to support a human interpreter with either interactive approaches, able to assist the interpreter with previously acquired expert knowledge about the domain in question, or AOR methods, capable of detecting, recognizing or analyzing certain classes of objects for certain sensors. We believe, to achieve an optimal result at the end of an interpretation process in terms of efficiency and effectivity, it is essential to integrate both interactive and automatic approaches to image interpretation. In this paper we present an approach inspired by the advancing semantic web technology to represent domain knowledge, the capabilities of available AOR modules and the image parameters in an explicit way. This enables us to seamlessly extend an interactive image interpretation environment with AOR modules in a way that we can automatically select suitable AOR methods for the current subtask, focus them on an appropriate area of interest and reintegrate their results into the environment.

  4. Selective electron capture into highly stripped Ne and N target atoms after heavy-ion impact

    International Nuclear Information System (INIS)

    Auger electron and x-ray spectra from Ne and N gas targets excited with 1.4 MeV amu-1 Ar12+, Kr15+, Xe24+, and Pb36+ ions are measured, varying the target pressure and mixing other gases into the target volume. A dramatic change of line intensities from outer-shell configurations having a KL two-electron core and a third electron in the n = 4,5,6 shell is observed, depending on the target pressure and systematically on the target ionisation potential. This effect is explained by highly selective electron capture from neutral target atoms or molecules into outer-shell orbitals of slowly (Esub(r) -14 cm2 is estimated from the experiment. (author)

  5. 自动液压压砖机液压油的选用%The Selection of Hydraulic Oil of Automatic Hydraulic Press for Ceramic Tiles

    Institute of Scientific and Technical Information of China (English)

    任小平; 汪建晓

    2001-01-01

    The types and characteristics of hydraulic oil are briefly introduced, and the selection methods of hydraulic oil of automatic hydraulic ress for ceramic tiles are presented.%本文简要介绍了液压油的类型和性能指标,阐述了全自动液压压砖机液压油的选用方法。

  6. Optimal systolic and diastolic coronary artery imaging with Dual-source CT: comparison of automatic optimal phase selection technique and whole phase reconstruction

    International Nuclear Information System (INIS)

    Objective: The purpose of this study was to evaluate the optimal reconstruction phase of dual-source CT coronary angiography (CTCA), and to compare image quality of CTCA using automatic optimal phase selection technique and whole phase reconstruction. Methods: 107 patients underwent CTCA Optimal systolic and diastolic coronary arteries were selected automatically, image quality was scored using four-score method. Coronary arteries were segmented according to the guideline of American Heart Association. Image quality of CTCA using both techniques was compared Results: Optimal image quality of CTCA was acquired at the 70% of R-R interval (average score of 3.11), followed by 75% and 35% of R- R interval (average scores of 3.06 and 3.03, respectively). Average score of optimal systolic phase was 305; while average score of optimal diastolic phase was 3.08. There was no significant difference between both techniques On the basis of per-segment, there was significant difference of image quality in segment 4 (p value of less than 0.05). On the basis of coronary artery, there was no significant difference between both techniques. Conclusion: Optimal diastolic and systolic image quality of CTCA was acquired at the 70% and 35% of R-R interval Automatic optimal phase selection technique can satisfy clinical demands because of its sufficient image quality; however, its combination of whole phase reconstruction technique is necessary. (authors)

  7. Selective focusing through target identification and experimental acoustic signature extraction: Numerical experiments.

    Science.gov (United States)

    Rodriguez, S; Jacob, X; Gibiat, V

    2016-05-01

    Using transducer arrays and appropriate emission delays allow to focus acoustic waves at a chosen location in a medium. The focusing spatial accuracy depends on the accurate knowledge of its acoustic properties. When those properties are unknown, methods based on the Time-Reversal principle allow accurate focusing. Still, these methods are either intrusive (an active source has to be introduced at the target location first), either blind (the target cannot be selected in the presence of several objects.) The purpose of the present work is to achieve non-invasive accurate focusing on a selected target using inaccurate acoustic properties for the investigated medium. Potential applications are for instance noninvasive surgery based on High Intensity Focused Ultrasound (HIFU). Numerical experiments are presented and demonstrate accurate focusing on a previously designated target located in an unknown heterogeneous medium. PMID:26890791

  8. An Approach for Automatic Orientation of Big Point Clouds from the Stationary Scanners Based on the Spherical Targets

    Directory of Open Access Journals (Sweden)

    YAO Jili

    2015-04-01

    Full Text Available Terrestrial laser scanning (TLS technology has high speed of data acquisition, large amount of point cloud, long distance of measuring. However, there are some disadvantages such as distance limitation in target detecting, hysteresis in point clouds processing, low automation and weaknesses of adapting long-distance topographic survey. In this case, we put forward a method on long-range targets detecting in big point clouds orientation. The method firstly searches point cloud rings that contain targets according to their engineering coordinate system. Then the detected rings are divided into sectors to detect targets in a very short time so as to obtain central coordinates of these targets. Finally, the position and orientation parameters of scanner are calculated and point clouds in scanner's own coordinate system(SOCS are converted into engineering coordinate system. The method is able to be applied in ordinary computers for long distance topographic(the distance between scanner and targets ranges from 180 to 700 m survey in mountainous areas with targets radius of 0.162m.

  9. Cysteine proteases as therapeutic targets: does selectivity matter? A systematic review of calpain and cathepsin inhibitors

    OpenAIRE

    Marton Siklos; Manel BenAissa; Thatcher, Gregory R.J.

    2015-01-01

    Cysteine proteases continue to provide validated targets for treatment of human diseases. In neurodegenerative disorders, multiple cysteine proteases provide targets for enzyme inhibitors, notably caspases, calpains, and cathepsins. The reactive, active-site cysteine provides specificity for many inhibitor designs over other families of proteases, such as aspartate and serine; however, a) inhibitor strategies often use covalent enzyme modification, and b) obtaining selectivity within families...

  10. Selection between Michaelis–Menten and target-mediated drug disposition pharmacokinetic models

    OpenAIRE

    Yan, Xiaoyu; Mager, Donald E.; Krzyzanski, Wojciech

    2009-01-01

    Target-mediated drug disposition (TMDD) models have been applied to describe the pharmacokinetics of drugs whose distribution and/or clearance are affected by its target due to high binding affinity and limited capacity. The Michaelis–Menten (M–M) model has also been frequently used to describe the pharmacokinetics of such drugs. The purpose of this study is to investigate conditions for equivalence between M–M and TMDD pharmacokinetic models and provide guidelines for selection between these...

  11. Target selection of classical pulsating variables for space-based photometry

    CERN Document Server

    Plachy, E; Szabó, R; Kolenberg, K; Bányai, E

    2016-01-01

    In a few years the Kepler and TESS missions will provide ultra-precise photometry for thousands of RR Lyrae and hundreds of Cepheid stars. In the extended Kepler mission all targets are proposed in the Guest Observer (GO) Program, while the TESS space telescope will work with full frame images and a ~15-16th mag brightness limit with the possibility of short cadence measurements for a limited number of pre-selected objects. This paper highlights some details of the enormous and important work of the target selection process made by the members of Working Group 7 (WG#7) of the Kepler and TESS Asteroseismic Science Consortium.

  12. Target selection of classical pulsating variables for space-based photometry

    Science.gov (United States)

    Plachy, E.; Molnar, L.; Szabo, R.; Kolenberg, K.; Banyai, E.

    2016-05-01

    In a few years the Kepler and TESS missions will provide ultra- precise photometry for thousands of RR Lyrae and hundreds of Cepheid stars. In the extended Kepler mission all targets are proposed in the Guest Observer (GO) Program, while the TESS space telescope will work with full frame images and a ~15-16th mag brightness limit with the possibility of short cadence measurements for a limited number of pre-selected objects. This paper highlights some details of the enormous and important work of the target selection process made by the members of Working Group 7 (WG#7) of the Kepler and TESS Asteroseismic Science Consortium.

  13. Average Minimum Transmit Power to achieve SINR Targets: Performance Comparison of Various User Selection Algorithms

    CERN Document Server

    Salim, Umer

    2010-01-01

    In multi-user communication from one base station (BS) to multiple users, the problem of minimizing the transmit power to achieve some target guaranteed performance (rates) at users has been well investigated in the literature. Similarly various user selection algorithms have been proposed and analyzed when the BS has to transmit to a subset of the users in the system, mostly for the objective of the sum rate maximization. We study the joint problem of minimizing the transmit power at the BS to achieve specific signal-to-interference-and-noise ratio (SINR) targets at users in conjunction with user scheduling. The general analytical results for the average transmit power required to meet guaranteed performance at the users' side are difficult to obtain even without user selection due to joint optimization required over beamforming vectors and power allocation scalars. We study the transmit power minimization problem with various user selection algorithms, namely semi-orthogonal user selection (SUS), norm-based...

  14. Hybrid EEG and eye movement interface to multi-directional target selection.

    Science.gov (United States)

    Kim, Minho; Chae, Yongwook; Jo, Sungho

    2013-01-01

    This work addresses the development of a low-cost hybrid interface with eye tracking and brain signals. Eye movement detection is used for search task and EEG-based brain computer interface (BCI) for selection task. Multi-directional target selection experiments with the hybrid interface device were conducted with five subjects to evaluate the proposed hybrid interface scheme. The task asked each user to move a cursor onto a circular target among twelve possible positions and select it. Using the Fitts' law, the interface performance was compared with the computer mouse. With two BCI selection confirmation schemes, the hybrid interface attained 2-2.7 bit/s overall. Based on the results, the potential of the proposed hybrid interface was discussed. PMID:24109799

  15. Nonstructural Proteins Are Preferential Positive Selection Targets in Zika Virus and Related Flaviviruses.

    Science.gov (United States)

    Sironi, Manuela; Forni, Diego; Clerici, Mario; Cagliani, Rachele

    2016-09-01

    The Flavivirus genus comprises several human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika virus (ZIKV). Although ZIKV usually causes mild symptoms, growing evidence is linking it to congenital birth defects and to increased risk of Guillain-Barré syndrome. ZIKV encodes a polyprotein that is processed to produce three structural and seven nonstructural (NS) proteins. We investigated the evolution of the viral polyprotein in ZIKV and in related flaviviruses (DENV, Spondweni virus, and Kedougou virus). After accounting for saturation issues, alignment uncertainties, and recombination, we found evidence of episodic positive selection on the branch that separates DENV from the other flaviviruses. NS1 emerged as the major selection target, and selected sites were located in immune epitopes or in functionally important protein regions. Three of these sites are located in an NS1 region that interacts with structural proteins and is essential for virion biogenesis. Analysis of the more recent evolutionary history of ZIKV lineages indicated that positive selection acted on NS5 and NS4B, this latter representing the preferential target. All selected sites were located in the N-terminal portion of NS4B, which inhibits interferon response. One of the positively selected sites (26M/I/T/V) in ZIKV also represents a selection target in sylvatic DENV2 isolates, and a nearby residue evolves adaptively in JEV. Two additional positively selected sites are within a protein region that interacts with host (e.g. STING) and viral (i.e. NS1, NS4A) proteins. Notably, mutations in the NS4B region of other flaviviruses modulate neurovirulence and/or neuroinvasiveness. These results suggest that the positively selected sites we identified modulate viral replication and contribute to immune evasion. These sites should be prioritized in future experimental studies. However, analyses herein detected no selective events associated to the spread of the Asian

  16. Selective attention modulates the effect of target location probability on redundant signal processing.

    Science.gov (United States)

    Chang, Ting-Yun; Little, Daniel R; Yang, Cheng-Ta

    2016-08-01

    We investigated the decision process underlying the detection of targets at multiple locations. In three experiments using the same observers, target location probability and attentional instructions were manipulated. A redundant-target detection task was conducted in which participants were required to detect a dot presented at one of two locations. When the dot appeared at the two locations with equal frequency (Experiment 1), those participants who were found to have limited to unlimited capacity were shown to adopt a parallel, self-terminating strategy. By contrast, those participants who had supercapacity were shown to process redundant targets in a coactive manner. When targets were presented with unequal probability, two participants adopted a parallel, self-terminating strategy regardless of whether they were informed the target location probability (Experiment 3) or not (Experiment 2). For the remaining two participants, the strategy changed from parallel, self-terminating to serial, self-terminating as a result of the probability instructions. In Experiments 2 and 3, all the participants were of unlimited to limited capacity. Taken together, these results suggest that target location probability differently affects the selection of a decision strategy and highlight the role of controlled attention in selecting a decision strategy. PMID:27188653

  17. Differential actions of insecticides on target sites: basis for selective toxicity

    OpenAIRE

    Narahashi, T; Zhao, X.; Ikeda, T; Nagata, K.(Faculty of Pure and Applied Sciences, University of Tsukuba, Tsukuba, Japan); Yeh, JZ

    2007-01-01

    Whereas the selective toxicity of insecticides between insects and mammals has a long history of studies, it is now becoming abundantly clear that, in many cases, the differential action of insecticides on insects and mammalian target receptor sites is an important factor. In this paper, we first introduce the mechanism of action and the selective toxicity of pyrethroids as a prototype of study. Then, a more detailed account is given for fipronil, based primarily on our recent studies. Pyreth...

  18. Targeted glycomics by selected reaction monitoring for highly sensitive glycan compositional analysis

    OpenAIRE

    Zhang, Hongquan; Wang, Zhaohui; Stupak, Jacek; Ghribi, Othman; Geiger, Jonathan D.; Liu, Qing Yan; Li, Jianjun

    2012-01-01

    The development of glycomics increasingly requires the detection and quantification of large numbers of glycans, which is only partially achieved by current glycomics approaches. Taking advantage of selected reaction monitoring to enhance both sensitivity and selectivity, we report here a strategy termed targeted glycomics that enables highly sensitive and consistent identification and quantification of diverse glycans across multiple samples at the same time. In this proof-of-principle study...

  19. Spectroscopic Target Selection in the Sloan Digital Sky Survey: The Quasar Sample

    OpenAIRE

    Richards, Gordon T.; Fan, Xiaohui; Newberg, Heidi Jo; Strauss, Michael A.; Berk, Daniel E. Vanden; Schneider, Donald P.; Yanny, Brian; Boucher, Adam; Burles, Scott; Frieman, Joshua A.; Gunn, James E.; Hall, Patrick B; Ivezic, Zeljko; Kent, Stephen; Loveday, Jon

    2002-01-01

    We describe the algorithm for selecting quasar candidates for optical spectroscopy in the Sloan Digital Sky Survey. Quasar candidates are selected via their non-stellar colors in "ugriz" broad-band photometry, and by matching unresolved sources to the FIRST radio catalogs. The automated algorithm is sensitive to quasars at all redshifts lower than z=5.8. Extended sources are also targeted as low-redshift quasar candidates in order to investigate the evolution of Active Galactic Nuclei (AGN) a...

  20. Selective Cancer Targeting via Aberrant Behavior of Cancer Cell-associated Glucocorticoid Receptor

    OpenAIRE

    Mukherjee, Amarnath; Narayan, Kumar P; Pal, Krishnendu; Kumar, Jerald M.; Rangaraj, Nandini; Shasi V Kalivendi; Banerjee, Rajkumar

    2009-01-01

    Glucocorticoid receptors (GRs) are ubiquitous, nuclear hormone receptors residing in cell types of both cancer and noncancerous origin. It is not known whether cancer cell–associated GR alone can be selectively manipulated for delivery of exogenous genes to its nucleus for eliciting anticancer effect. We find that GR ligand, dexamethasone (Dex) in association with cationic lipoplex (termed as targeted lipoplex) could selectively manipulate GR in cancer cells alone for the delivery of transgen...

  1. The evaluation of the performance of the automatic exposure control system of some selected mammography facilities in the Greater Accra Region, Ghana

    International Nuclear Information System (INIS)

    Mammography aids in the early detection of breast cancer. X-rays has an associated risk of inducing cancer though very useful and as such mammography procedures should be optimized through the appropriate processes such as the selection of exposure factors for an optimum image and minimal dose to patients. The automatic exposure control (AEC) aids in the selection of exposure factors thus controlling the amount of radiation to the breast and automatically compensates for differences in the breast thickness and density. The performance of the automatic exposure control system of mammography equipment and the status of quality management systems including quality assurance and quality controls of four (4) mammography facilities within the Greater Accra Region were assessed. In assessing the performance of the automatic exposure control system, the short term reproducibility test, thickness and voltage compensation test were carried out using breast equivalent phantom of various thicknesses. Half value layer test, film reject analysis and patient dose assessment were also performed. Analysis of the responses of the questionnaire administered to radiographers and supervisors of the selected facilities revealed that three (3) of the facilities have some aspect of quality management system programme in place but not effectively implemented. Measured optical densities from the various tests performed to evaluate the performance of the automatic exposure control systems revealed that the AEC compensates for the different phantom thickness and tube voltage (KV) by producing comparable optical densities for the various phantom thickness and tube voltages. Some of the measured optical densities were within the recommended optical density range of 1.5 OD - 1.9 OD. The highest optical density value was 0.13 OD above the highest limit of 1.9 OD. The film reject analysis showed that patient motion accounted for the large part (28%) of film rejects. Other factors such as too light

  2. The SDSS-IV extended Baryonic Oscillation Spectroscopic Survey: Luminous Red Galaxy Target Selection

    CERN Document Server

    Prakash, Abhishek; Newman, Jeffrey A; Ross, Ashley J; Myers, Adam D; Dawson, Kyle S; Kneib, Jean-Paul; Percival, Will J; Bautista, Julian E; Comparat, Johan; Tinker, Jeremy L; Schlegel, David J; Tojeiro, Rita; Ho, Shirley; Lang, Dustin; Rao, Sandhya M; McBride, Cameron K; Zhu, Guangtun Ben; Brownstein, Joel R; Bailey, Stephen; Bolton, Adam S; Delubac, Timothee; Mariappan, Vivek; Blanton, Michael R; Reid, Beth; Schneider, Donald P; Seo, Hee-Jong; Rosell, Aurelio Carnero; Prada, Francisco

    2015-01-01

    We describe the algorithm used to select the Luminous Red Galaxy (LRG) sample for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV) using photometric data from both the SDSS and the Wide-Field Infrared Survey Explorer (WISE). LRG targets are required to meet a set of color selection criteria and have z-band and i-band MODEL magnitudes z < 19.95 and 19.9 < i < 21.8, respectively. Our algorithm selects roughly 50 LRG targets per square degree, the great majority of which lie in the redshift range 0.6 < z < 1.0 (median redshift 0.71). We demonstrate that our methods are highly effective at eliminating stellar contamination and lower-redshift galaxies. We perform a number of tests using spectroscopic data from SDSS-III/BOSS to determine the redshift reliability of our target selection and its ability to meet the science requirements of eBOSS. The SDSS spectra are of high enough signal-to-noise ratio that at least 89% of the target sample yield...

  3. Target Selection for the Arecibo Pisces-Perseus Supercluster Survey (APPSS)

    Science.gov (United States)

    Craig, David W.; O'Donoghue, Aileen A.; Haynes, Martha P.; Rosenberg, Jessica L.; Venkatesan, Aparna; Hallenbeck, Gregory L.; Jones, Michael; Koopmann, Rebecca A.; Undergraduate ALFALFA Team

    2016-01-01

    The Arecibo Pisces-Perseus Supercluster Survey (APPSS) is a new large targeted HI survey now underway using Arecibo's L-band Wide receiver system. A major goal is to constrain models of the Pisces Perseus infall, producing 5-σ detections of infall motions ˜500 km s-1. We are targeting sources that are likely to be at the PPS distance, but that are just below the the HI mass detection threshold of the ALFALFA survey. We expect to identify ˜800 objects of mass ˜108—9 M⊙ which will alllow us to constrain the lower mass end of the HI mass function in this infall environment.We have pursued a multi-pronged approach to target selection for this survey. Sources from ALFALFA, SDSS, and the GALEX GCAT single source catalogs were matched and intercompared via multi-band color photometry, surface brightnesses, and appearance in SDSS images. Final target selection based on visual inspection of SDSS images was found to correlate well with a color-selection technique based on GALEX/NUV - SDSS/r. Along with the details of the source selection we will discuss the facilitation and implementation of this process via a multi-institution collaborative website, and early results from the APSS survey.This work has been supported by NSF grant AST-1211005.

  4. Joint Effect of Insertion of Spaces and Word Length in Saccade Target Selection in Chinese Reading

    Science.gov (United States)

    Li, Xingshan; Shen, Wei

    2013-01-01

    The present study examined how insertion of spaces before and after a word affects saccade target selection in Chinese reading. We found that inserting spaces in Chinese text changes the eye movement behaviour of Chinese readers. They are less likely to fixate on the character near the space and will try their best to process the entire word with…

  5. Photometric Observations of Selected BRITE Target Stars at Mt. Suhora Observatory

    Science.gov (United States)

    Stachowski, G.; Ogloza, W.; Drozdz, M.; Zakrzewski, B.

    2015-07-01

    We present the results of ground-based photometric observations of selected bright stars targeted by the BRITE satellite mission, carried out at Mt. Suhora Observatory using the new small telescope and a CCD camera, with the chip partially covered by a neutral density filter.

  6. The SDSS-IV Extended Baryon Oscillation Spectroscopic Survey: Luminous Red Galaxy Target Selection

    Science.gov (United States)

    Prakash, Abhishek; Licquia, Timothy C.; Newman, Jeffrey A.; Ross, Ashley J.; Myers, Adam D.; Dawson, Kyle S.; Kneib, Jean-Paul; Percival, Will J.; Bautista, Julian E.; Comparat, Johan; Tinker, Jeremy L.; Schlegel, David J.; Tojeiro, Rita; Ho, Shirley; Lang, Dustin; Rao, Sandhya M.; McBride, Cameron K.; Ben Zhu, Guangtun; Brownstein, Joel R.; Bailey, Stephen; Bolton, Adam S.; Delubac, Timothée; Mariappan, Vivek; Blanton, Michael R.; Reid, Beth; Schneider, Donald P.; Seo, Hee-Jong; Carnero Rosell, Aurelio; Prada, Francisco

    2016-06-01

    We describe the algorithm used to select the luminous red galaxy (LRG) sample for the extended Baryon Oscillation Spectroscopic Survey (eBOSS) of the Sloan Digital Sky Survey IV (SDSS-IV) using photometric data from both the SDSS and the Wide-field Infrared Survey Explorer. LRG targets are required to meet a set of color selection criteria and have z-band and i-band MODEL magnitudes z < 19.95 and 19.9 < i < 21.8, respectively. Our algorithm selects roughly 50 LRG targets per square degree, the great majority of which lie in the redshift range 0.6 < z < 1.0 (median redshift 0.71). We demonstrate that our methods are highly effective at eliminating stellar contamination and lower-redshift galaxies. We perform a number of tests using spectroscopic data from SDSS-III/BOSS ancillary programs to determine the redshift reliability of our target selection and its ability to meet the science requirements of eBOSS. The SDSS spectra are of high enough signal-to-noise ratio that at least ∼89% of the target sample yields secure redshift measurements. We also present tests of the uniformity and homogeneity of the sample, demonstrating that it should be clean enough for studies of the large-scale structure of the universe at higher redshifts than SDSS-III/BOSS LRGs reached.

  7. Sequence-selective targeting of duplex DNA by peptide nucleic acids

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    nucleic acid (PNA) can recognize duplex DNA with high sequence specificity and affinity in triplex, duplex and double-duplex invasive modes or non-invasive triplex modes. Novel PNA modification has improved the affinity for DNA recognition via duplex invasion, double-duplex invasion and triplex......Sequence-selective gene targeting constitutes an attractive drug-discovery approach for genetic therapy, with the aim of reducing or enhancing the activity of specific genes at the transcriptional level, or as part of a methodology for targeted gene repair. The pseudopeptide DNA mimic peptide...... recognition considerably. Such modifications have also resulted in new approaches to targeted gene repair and sequence-selective double-strand cleavage of genomic DNA....

  8. Patient selection and targeted treatment in the management of platinum-resistant ovarian cancer

    Directory of Open Access Journals (Sweden)

    Leamon PC

    2013-09-01

    Full Text Available Christopher P Leamon,1 Chandra D Lovejoy,2 Binh Nguyen3 1Research and Development, 2Regulatory Affairs, 3Clinical Affairs, Endocyte Inc, West Lafayette, IN, USA Abstract: Ovarian cancer (OC has the highest mortality rate of any gynecologic cancer, and patients generally have a poor prognosis due to high chemotherapy resistance and late stage disease diagnosis. Platinum-resistant OC can be treated with cytotoxic chemotherapy such as paclitaxel, topotecan, pegylated liposomal doxorubicin, and gemcitabine, but many patients eventually relapse upon treatment. Fortunately, there are currently a number of targeted therapies in development for these patients who have shown promising results in recent clinical trials. These treatments often target the vascular endothelial growth factor pathway (eg, bevacizumab and aflibercept, DNA repair mechanisms (eg, iniparib and olaparib, or they are directed against folate related pathways (eg, pemetrexed, farletuzumab, and vintafolide. As many targeted therapies are only effective in a subset of patients, there is an increasing need for the identification of response predictive biomarkers. Selecting the right patients through biomarker screening will help tailor therapy to patients and decrease superfluous treatment to those who are biomarker negative; this approach should lead to improved clinical results and decreased toxicities. In this review the current targeted therapies used for treating platinum-resistant OC are discussed. Furthermore, use of prognostic and response predictive biomarkers to define OC patient populations that may benefit from specific targeted therapies is also highlighted. Keywords: platinum-resistant ovarian cancer, targeted therapy, patient selection, folate receptor, VEGF, biomarkers

  9. Impact of planning CT slice thickness on the accuracy of automatic target registration using the on-board cone-beam CT

    International Nuclear Information System (INIS)

    We have evaluated relationship between planning CT slice thickness and the accuracy of automatic target registration using cone-beam CT (CBCT). Planning CT images were acquired with reconstructed slice thickness of 1, 2, 3, 5, and 10 mm for three different phantoms: Penta-Guide phantom, acrylic ball phantom, and pelvic phantom. After correctly placing the phantom at the isocenter using an in-room laser, we purposely displaced it by moving the treatment couch and then obtained CBCT images. Registration between the planning CT and the CBCT was performed using automatic target registration software, and the registration errors were recorded for each planning CT data set with different slice thickness. The respective average and standard deviation of errors for 10 mm slice thickness CT in the lateral, longitudinal, and vertical directions (n=15 data sets) were: 0.7±0.2 mm, 0.8±0.2 mm, and 0.2±0.2 mm for the Penta-Guide phantom; 0.5±0.4 mm, 0.6±0.3 mm, and 0.4±0.3 mm for the acrylic ball phantom and 0.6±0.2 mm, 0.9±0.2 mm, and 0.2±0.2 mm for the pelvic phantom. We found that the mean registration errors were always less than 1 mm regardless of the slice thickness tested. The results suggest that there is no obvious correlation between the planning CT slice thickness and the registration errors. (author)

  10. 采用多特征融合的自动适配区选择方法%Automatic suitable-matching area selection method based on multi-feature fusion

    Institute of Scientific and Technical Information of China (English)

    罗海波; 常铮; 余新荣; 丁庆海

    2011-01-01

    Target tracking with local non-texture is a difficult point and hot topic in the field of ground imaging guidance. Since the automatic suitable-matching area selection is an effective method to solve this problem, an algorithm of automatic suitable-matching area selection based on multi-feature fusion was proposed. Firstly, the edge density, the average edge strength, the edge direction dispersion degree andthe space distance were integrated to form a suitable-matching measure function. Then, the credibility of suitable-matching of each point in the image was calculated by this function. Lastly, through developing adaptive selection strategy to the suitable-matching area, three suitable-matching areas with high credibility were segmented as target template for matching tracking. Experimental results show that the segmented suitable-matching area with proposed algorithm can achieve more tracking precision compared with the results judged by the human experience. This proposed algorithm can be widely used in the applications of the ground imaging-guided target tracking with local non-texture target and the scene matching task planning.%局部无纹理目标跟踪是当今空地成像制导领域的一个难点和热点问题,而自动适配区选择是解决该难题的一种有效方法.介绍了一种基于多特征融合的自动适配区选择方法.首先,构造一个融合边缘密度、平均边缘强度、边缘方向离散度以及空间距离的适配性度量函数;然后,采用该函数计算图像中每一点的适配置信度;通过制定适当的适配区选择策略,分割出3个置信度相对较高的适配区,用作匹配跟踪的目标模板.实验结果表明,采用该方法分割出的适配区与通过人工经验判断的结果相近,获得了较好的结果.该方法可广泛用于空地成像制导的局部无纹理目标跟踪以及景象匹配任务规划等应用中.

  11. THE SDSS-III BARYON OSCILLATION SPECTROSCOPIC SURVEY: QUASAR TARGET SELECTION FOR DATA RELEASE NINE

    International Nuclear Information System (INIS)

    The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg2, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations (BAOs) in the distribution of Lyα absorption from the spectra of a sample of ∼150,000 z > 2.2 quasars. Along with measuring the angular diameter distance at z ≈ 2.5, BOSS will provide the first direct measurement of the expansion rate of the universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars in the redshift range 2.2 –2 in this redshift range, with a goal of 20 out of 40 targets deg–2 allocated to the quasar survey. To achieve these surface densities, the magnitude limit of the quasar targets was set at g ≤ 22.0 or r ≤ 21.85. While detection of the BAO signature in the distribution of Lyα absorption in quasar spectra does not require a uniform target selection algorithm, many other astrophysical studies do. We have therefore defined a uniformly selected subsample of 20 targets deg–2, for which the selection efficiency is just over 50% (∼10 z > 2.20 quasars deg–2). This 'CORE' subsample will be fixed for Years Two through Five of the survey. For the remaining 20 targets deg–2, we will continue to develop improved selection techniques, including the use of additional data sets beyond the Sloan Digital Sky Survey (SDSS) imaging data. In this paper, we describe the evolution and implementation of the BOSS QTS algorithms during the first two years of BOSS operations (through 2011 July), in support of the science investigations based on these data, and we analyze the spectra obtained during the first year. During this year, 11,263 new z > 2.20 quasars were spectroscopically confirmed by BOSS, roughly double the number of previously known quasars with z > 2.20. Our current algorithms select an average of 15 z > 2.20 quasars deg–2 from 40

  12. MLENN-KELM: a Prototype Selection Based Kernel Extreme Learning Machine Approach for Large-Scale Automatic Image Annotation

    OpenAIRE

    Hamid Kargar-Shooroki; Mohammad Ali Zare Chahooki; Shima Javanmardi

    2015-01-01

    With the fast growth of digital images in web, large-scale Automatic Image Annotation (AIA) dealt with some of critical challenges. The most important of them are system scalability and annotation performance. On the other hand, learning methods in the large-scale systems with the large number of training instances cannot correctly perform and deal with memory and learning time restrictions. In this paper in order to solve the performance of large-scale AIA systems, and limitations of employi...

  13. Target selection by the frontal cortex during coordinated saccadic and smooth pursuit eye movements.

    Science.gov (United States)

    Srihasam, Krishna; Bullock, Daniel; Grossberg, Stephen

    2009-08-01

    Oculomotor tracking of moving objects is an important component of visually based cognition and planning. Such tracking is achieved by a combination of saccades and smooth-pursuit eye movements. In particular, the saccadic and smooth-pursuit systems interact to often choose the same target, and to maximize its visibility through time. How do multiple brain regions interact, including frontal cortical areas, to decide the choice of a target among several competing moving stimuli? How is target selection information that is created by a bias (e.g., electrical stimulation) transferred from one movement system to another? These saccade-pursuit interactions are clarified by a new computational neural model, which describes interactions between motion processing areas: the middle temporal area, the middle superior temporal area, the frontal pursuit area, and the dorsal lateral pontine nucleus; saccade specification, selection, and planning areas: the lateral intraparietal area, the frontal eye fields, the substantia nigra pars reticulata, and the superior colliculus; the saccadic generator in the brain stem; and the cerebellum. Model simulations explain a broad range of neuroanatomical and neurophysiological data. These results are in contrast with the simplest parallel model with no interactions between saccades and pursuit other than common-target selection and recruitment of shared motoneurons. Actual tracking episodes in primates reveal multiple systematic deviations from predictions of the simplest parallel model, which are explained by the current model. PMID:18823247

  14. Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells.

    Directory of Open Access Journals (Sweden)

    Idit Dotan

    Full Text Available The incidence of papillary thyroid carcinoma (PTC has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches.Thyroid Stimulating Hormone Receptor (TSHR was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining.TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls.A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam radiation or chemotherapy, with

  15. In vitro Selection and Interaction Studies of a DNA Aptamer Targeting Protein A.

    Directory of Open Access Journals (Sweden)

    Regina Stoltenburg

    Full Text Available A new DNA aptamer targeting Protein A is presented. The aptamer was selected by use of the FluMag-SELEX procedure. The SELEX technology (Systematic Evolution of Ligands by EXponential enrichment is widely applied as an in vitro selection and amplification method to generate target-specific aptamers and exists in various modified variants. FluMag-SELEX is one of them and is characterized by the use of magnetic beads for target immobilization and fluorescently labeled oligonucleotides for monitoring the aptamer selection progress. Structural investigations and sequence truncation experiments of the selected aptamer for Protein A led to the conclusion, that a stem-loop structure at its 5'-end including the 5'-primer binding site is essential for aptamer-target binding. Extensive interaction analyses between aptamer and Protein A were performed by methods like surface plasmon resonance, MicroScale Thermophoresis and bead-based binding assays using fluorescence measurements. The binding of the aptamer to its target was thus investigated in assays with immobilization of one of the binding partners each, and with both binding partners in solution. Affinity constants were determined in the low micromolar to submicromolar range, increasing to the nanomolar range under the assumption of avidity. Protein A provides more than one binding site for the aptamer, which may overlap with the known binding sites for immunoglobulins. The aptamer binds specifically to both native and recombinant Protein A, but not to other immunoglobulin-binding proteins like Protein G and L. Cross specificity to other proteins was not found. The application of the aptamer is directed to Protein A detection or affinity purification. Moreover, whole cells of Staphylococcus aureus, presenting Protein A on the cell surface, could also be bound by the aptamer.

  16. Engineering Multi-Walled Carbon Nanotube Therapeutic Bionanofluids to Selectively Target Papillary Thyroid Cancer Cells

    Science.gov (United States)

    Paliouras, Miltiadis; Mitmaker, Elliot J.; Trifiro, Mark A.

    2016-01-01

    Background The incidence of papillary thyroid carcinoma (PTC) has risen steadily over the past few decades as well as the recurrence rates. It has been proposed that targeted ablative physical therapy could be a therapeutic modality in thyroid cancer. Targeted bio-affinity functionalized multi-walled carbon nanotubes (BioNanofluid) act locally, to efficiently convert external light energy to heat thereby specifically killing cancer cells. This may represent a promising new cancer therapeutic modality, advancing beyond conventional laser ablation and other nanoparticle approaches. Methods Thyroid Stimulating Hormone Receptor (TSHR) was selected as a target for PTC cells, due to its wide expression. Either TSHR antibodies or Thyrogen or purified TSH (Thyrotropin) were chemically conjugated to our functionalized Bionanofluid. A diode laser system (532 nm) was used to illuminate a PTC cell line for set exposure times. Cell death was assessed using Trypan Blue staining. Results TSHR-targeted BioNanofluids were capable of selectively ablating BCPAP, a TSHR-positive PTC cell line, while not TSHR-null NSC-34 cells. We determined that a 2:1 BCPAP cell:α-TSHR-BioNanofluid conjugate ratio and a 30 second laser exposure killed approximately 60% of the BCPAP cells, while 65% and >70% of cells were ablated using Thyrotropin- and Thyrogen-BioNanofluid conjugates, respectively. Furthermore, minimal non-targeted killing was observed using selective controls. Conclusion A BioNanofluid platform offering a potential therapeutic path for papillary thyroid cancer has been investigated, with our in vitro results suggesting the development of a potent and rapid method of selective cancer cell killing. Therefore, BioNanofluid treatment emphasizes the need for new technology to treat patients with local recurrence and metastatic disease who are currently undergoing either re-operative neck explorations, repeated administration of radioactive iodine and as a last resort external beam

  17. A procedure for extending input selection algorithms to low quality data in modelling problems with application to the automatic grading of uploaded assignments.

    Science.gov (United States)

    Otero, José; Palacios, Ana; Suárez, Rosario; Junco, Luis; Couso, Inés; Sánchez, Luciano

    2014-01-01

    When selecting relevant inputs in modeling problems with low quality data, the ranking of the most informative inputs is also uncertain. In this paper, this issue is addressed through a new procedure that allows the extending of different crisp feature selection algorithms to vague data. The partial knowledge about the ordinal of each feature is modelled by means of a possibility distribution, and a ranking is hereby applied to sort these distributions. It will be shown that this technique makes the most use of the available information in some vague datasets. The approach is demonstrated in a real-world application. In the context of massive online computer science courses, methods are sought for automatically providing the student with a qualification through code metrics. Feature selection methods are used to find the metrics involved in the most meaningful predictions. In this study, 800 source code files, collected and revised by the authors in classroom Computer Science lectures taught between 2013 and 2014, are analyzed with the proposed technique, and the most relevant metrics for the automatic grading task are discussed. PMID:25114967

  18. A Procedure for Extending Input Selection Algorithms to Low Quality Data in Modelling Problems with Application to the Automatic Grading of Uploaded Assignments

    Directory of Open Access Journals (Sweden)

    José Otero

    2014-01-01

    Full Text Available When selecting relevant inputs in modeling problems with low quality data, the ranking of the most informative inputs is also uncertain. In this paper, this issue is addressed through a new procedure that allows the extending of different crisp feature selection algorithms to vague data. The partial knowledge about the ordinal of each feature is modelled by means of a possibility distribution, and a ranking is hereby applied to sort these distributions. It will be shown that this technique makes the most use of the available information in some vague datasets. The approach is demonstrated in a real-world application. In the context of massive online computer science courses, methods are sought for automatically providing the student with a qualification through code metrics. Feature selection methods are used to find the metrics involved in the most meaningful predictions. In this study, 800 source code files, collected and revised by the authors in classroom Computer Science lectures taught between 2013 and 2014, are analyzed with the proposed technique, and the most relevant metrics for the automatic grading task are discussed.

  19. Target selection and comparison of mission design for space debris removal by DLR's advanced study group

    Science.gov (United States)

    van der Pas, Niels; Lousada, Joao; Terhes, Claudia; Bernabeu, Marc; Bauer, Waldemar

    2014-09-01

    Space debris is a growing problem. Models show that the Kessler syndrome, the exponential growth of debris due to collisions, has become unavoidable unless an active debris removal program is initiated. The debris population in LEO with inclination between 60° and 95° is considered as the most critical zone. In order to stabilize the debris population in orbit, especially in LEO, 5 to 10 objects will need to be removed every year. The unique circumstances of such a mission could require that several objects are removed with a single launch. This will require a mission to rendezvous with a multitude of objects orbiting on different altitudes, inclinations and planes. Removal models have assumed that the top priority targets will be removed first. However this will lead to a suboptimal mission design and increase the ΔV-budget. Since there is a multitude of targets to choose from, the targets can be selected for an optimal mission design. In order to select a group of targets for a removal mission the orbital parameters and political constraints should also be taken into account. Within this paper a number of the target selection criteria are presented. The possible mission targets and their order of retrieval is dependent on the mission architecture. A comparison between several global mission architectures is given. Under consideration are 3 global missions of which a number of parameters are varied. The first mission launches multiple separate deorbit kits. The second launches a mother craft with deorbit kits. The third launches an orbital tug which pulls the debris in a lower orbit, after which a deorbit kit performs the final deorbit burn. A RoM mass and cost comparison is presented. The research described in this paper has been conducted as part of an active debris removal study by the Advanced Study Group (ASG). The ASG is an interdisciplinary student group working at the DLR, analyzing existing technologies and developing new ideas into preliminary

  20. ROBIN: a platform for evaluating automatic target recognition algorithms: I. Overview of the project and presentation of the SAGEM DS competition

    Science.gov (United States)

    Duclos, D.; Lonnoy, J.; Guillerm, Q.; Jurie, F.; Herbin, S.; D'Angelo, E.

    2008-04-01

    The last five years have seen a renewal of Automatic Target Recognition applications, mainly because of the latest advances in machine learning techniques. In this context, large collections of image datasets are essential for training algorithms as well as for their evaluation. Indeed, the recent proliferation of recognition algorithms, generally applied to slightly different problems, make their comparisons through clean evaluation campaigns necessary. The ROBIN project tries to fulfil these two needs by putting unclassified datasets, ground truths, competitions and metrics for the evaluation of ATR algorithms at the disposition of the scientific community. The scope of this project includes single and multi-class generic target detection and generic target recognition, in military and security contexts. From our knowledge, it is the first time that a database of this importance (several hundred thousands of visible and infrared hand annotated images) has been publicly released. Funded by the French Ministry of Defence (DGA) and by the French Ministry of Research, ROBIN is one of the ten Techno-vision projects. Techno-vision is a large and ambitious government initiative for building evaluation means for computer vision technologies, for various application contexts. ROBIN's consortium includes major companies and research centres involved in Computer Vision R&D in the field of defence: Bertin Technologies, CNES, ECA, DGA, EADS, INRIA, ONERA, MBDA, SAGEM, THALES. This paper, which first gives an overview of the whole project, is focused on one of ROBIN's key competitions, the SAGEM Defence Security database. This dataset contains more than eight hundred ground and aerial infrared images of six different vehicles in cluttered scenes including distracters. Two different sets of data are available for each target. The first set includes different views of each vehicle at close range in a "simple" background, and can be used to train algorithms. The second set

  1. The use of selection in recovery of transgenic targets for mutation analysis.

    Science.gov (United States)

    Lundberg, K S; Kretz, P L; Provost, G S; Short, J M

    1993-02-01

    Transgenic animal mutagenesis assays using lambda shuttle vectors have recently been described for isolation and characterization of spontaneous and chemical induced DNA mutations. Extensive information on lambda and E. coli genetics provides a wealth of techniques to allow selection of mutant target genes. Here we describe the modification of an E. coli host which permits two methods for the direct selection of mutant genes. These methods reduce the number of plates needed to be screened for a comparable amount of frequency data by 20-100-fold and thus provide a significant savings of the materials and time required for the screening of mutations. In addition, mutants selected by these approaches described here may alter or broaden the spectrum of mutations that are recoverable. Ultimately, a combination of selective and nonselective techniques may prove valuable for the analysis of mutations produced in vivo in transgenic animals. PMID:7678177

  2. Selective pressures for accurate altruism targeting: evidence from digital evolution for difficult-to-test aspects of inclusive fitness theory

    OpenAIRE

    Clune, Jeff; Goldsby, Heather J.; Ofria, Charles; Pennock, Robert T

    2010-01-01

    Inclusive fitness theory predicts that natural selection will favour altruist genes that are more accurate in targeting altruism only to copies of themselves. In this paper, we provide evidence from digital evolution in support of this prediction by competing multiple altruist-targeting mechanisms that vary in their accuracy in determining whether a potential target for altruism carries a copy of the altruist gene. We compete altruism-targeting mechanisms based on (i) kinship (kin targeting),...

  3. The SDSS-IV extended Baryon Oscillation Spectroscopic Survey: Quasar Target Selection

    OpenAIRE

    Myers, Adam D.; Palanque-Delabrouille, Nathalie; Prakash, Abhishek; Pâris, Isabelle; Yeche, Christophe,; Dawson, Kyle S.; Bovy, Jo; Lang, Dustin; Schlegel, David J.; Newman, Jeffrey A.; Petitjean, Patrick; Kneib, Jean Paul; Laurent, Pierre; Percival, Will J.; Ross, Ashley J.

    2015-01-01

    As part of the Sloan Digital Sky Survey IV the extended Baryon Oscillation Spectroscopic Survey (eBOSS) will improve measurements of the cosmological distance scale by applying the Baryon Acoustic Oscillation (BAO) method to quasar samples. eBOSS will adopt two approaches to target quasars over 7500 sq. deg. First, a "CORE" quasar sample will combine optical selection in ugriz using a likelihood-based routine called XDQSOz, with a mid-IR-optical color-cut. eBOSS CORE selection (to g < 22 OR r...

  4. The contribution of the major planet search surveys to EChO target selection

    CERN Document Server

    Micela, Giuseppina; Lopez-Morales, Mercedes; Maxted, Pierre F L; Pagano, Isabella; Sozzetti, Alessandro; Wheatley, Peter J

    2014-01-01

    The EChO core science will be based on a three tier survey, each with increasing sensitivity, in order to study the population of exo-planets from super-Earths to Jupiter-like planets, in the very hot to temperate zones (temperatures of 300 K - 3000 K) of F to M-type host stars. To achieve a meaningful outcome an accurate selection of the target sample is needed. In this paper we analyse the targets, suitable for EChO observations, expected to result from a sample of present and forthcoming detection surveys. Exoplanets currently known are already sufficient to provide a large and diverse sample. However we expect the results from these surveys to increase the sample of smaller planets that will allow us to optimize the EChO sample selection.

  5. Impact of high-risk conjunctions on Active Debris Removal target selection

    Science.gov (United States)

    Lidtke, Aleksander A.; Lewis, Hugh G.; Armellin, Roberto

    2015-10-01

    Space debris simulations show that if current space launches continue unchanged, spacecraft operations might become difficult in the congested space environment. It has been suggested that Active Debris Removal (ADR) might be necessary in order to prevent such a situation. Selection of objects to be targeted by ADR is considered important because removal of non-relevant objects will unnecessarily increase the cost of ADR. One of the factors to be used in this ADR target selection is the collision probability accumulated by every object. This paper shows the impact of high-probability conjunctions on the collision probability accumulated by individual objects as well as the probability of any collision occurring in orbit. Such conjunctions cannot be predicted far in advance and, consequently, not all the objects that will be involved in such dangerous conjunctions can be removed through ADR. Therefore, a debris remediation method that would address such events at short notice, and thus help prevent likely collisions, is suggested.

  6. Time-Inconsistent Mean-Utility Portfolio Selection with Moving Target

    OpenAIRE

    Hanqing Jin; Yimin Yang

    2014-01-01

    In this paper, we solve the time inconsistent portfolio selection problem by using different utility functions with a moving target as our constraint. We solve this problem by finding an equilibrium control under the given definition as our optimal control. We firstly derive a sufficient equilibrium condition for second-order continuously differentiable utility funtions. Then we use power functions of order two, three and four in our problem and find the respective condtions for obtaining an ...

  7. Targeted energy transfer between a Rotor and a Morse oscillator: A model for selective chemical dissociation

    OpenAIRE

    Memboeuf, Antony; Aubry, Serge

    2005-01-01

    Standard Kramers theory of chemical reactions involves a coupling with a Langevin thermal bath which intrinsically forbids the possible existence of Discrete Breathers (DBs) (i.e. local modes). However, it is now known that in complex systems, that energy may focus for long time as Discrete Breathers (local mode). In very special systems, targeted energy transfer may occur subsequently to another selected site and induces an ultraselective chemical reaction operating at low temperature. The d...

  8. Automatic sequences

    CERN Document Server

    Haeseler, Friedrich

    2003-01-01

    Automatic sequences are sequences which are produced by a finite automaton. Although they are not random they may look as being random. They are complicated, in the sense of not being not ultimately periodic, they may look rather complicated, in the sense that it may not be easy to name the rule by which the sequence is generated, however there exists a rule which generates the sequence. The concept automatic sequences has special applications in algebra, number theory, finite automata and formal languages, combinatorics on words. The text deals with different aspects of automatic sequences, in particular:· a general introduction to automatic sequences· the basic (combinatorial) properties of automatic sequences· the algebraic approach to automatic sequences· geometric objects related to automatic sequences.

  9. Retroviral DNA integration: viral and cellular determinants of target-site selection.

    Directory of Open Access Journals (Sweden)

    Mary K Lewinski

    2006-06-01

    Full Text Available Retroviruses differ in their preferences for sites for viral DNA integration in the chromosomes of infected cells. Human immunodeficiency virus (HIV integrates preferentially within active transcription units, whereas murine leukemia virus (MLV integrates preferentially near transcription start sites and CpG islands. We investigated the viral determinants of integration-site selection using HIV chimeras with MLV genes substituted for their HIV counterparts. We found that transferring the MLV integrase (IN coding region into HIV (to make HIVmIN caused the hybrid to integrate with a specificity close to that of MLV. Addition of MLV gag (to make HIVmGagmIN further increased the similarity of target-site selection to that of MLV. A chimeric virus with MLV Gag only (HIVmGag displayed targeting preferences different from that of both HIV and MLV, further implicating Gag proteins in targeting as well as IN. We also report a genome-wide analysis indicating that MLV, but not HIV, favors integration near DNase I-hypersensitive sites (i.e., +/- 1 kb, and that HIVmIN and HIVmGagmIN also favored integration near these features. These findings reveal that IN is the principal viral determinant of integration specificity; they also reveal a new role for Gag-derived proteins, and strengthen models for integration targeting based on tethering of viral IN proteins to host proteins.

  10. BLAST: Battery Lifetime-constrained Adaptation with Selected Target in Mobile Devices

    Directory of Open Access Journals (Sweden)

    Pietro Mercati

    2015-08-01

    Full Text Available Mobile devices today contain many power hungry subsystems and execute different applications. Standard power management is not aware of the desired battery lifetime and has no visibility into which applications are executing. However, power consumption is strongly dependent on which applications are executed. In this work, we propose a novel power characterization strategy for mobile devices called application-dependent power states (AP-states. Based on that, we formulate a management problem to improve performance under battery lifetime constraints, and we implement the management framework on a real Android device. We call our framework BLAST: Battery Lifetime-constrained Adaptation with Selected Target. The goal of such framework is to maximize performance while letting the device battery to last at least for a certain required lifetime, and only requires the user to select the desired target lifetime. The implementation does not require OS modifications and can be ported and installed to any Android device. We experimentally verify that our strategy can still meets user experience requirements with a selected target battery lifetime extension of at least 25%.

  11. Selective autophagy of non-ubiquitylated targets in plants: looking for cognate receptor/adaptor proteins

    Directory of Open Access Journals (Sweden)

    Vasko eVeljanovski

    2014-06-01

    Full Text Available Cellular homeostasis is essential for the physiology of eukaryotic cells. Eukaryotic cells, including plant cells, utilize two main pathways to adjust the level of cytoplasmic components, namely the proteasomal and the lysosomal/vacuolar pathways. Macroautophagy is a lysosomal/vacuolar pathway which, until recently, was thought to be non-specific and a bulk degradation process. However, selective autophagy which can be activated in the cell under various physiological conditions, involves the specific degradation of defined macromolecules or organelles by a conserved molecular mechanism. For this process to be efficient, the mechanisms underlying the recognition and selection of the cargo to be engulfed by the double-membrane autophagosome are critical, and not yet well understood. Ubiquitin (poly-ubiquitin conjugation to the target appears to be a conserved ligand mechanism in many types of selective autophagy, and defined receptors/adaptors recognizing and regulating the autophagosomal capture of the ubiquitylated target have been characterized. However, non-proteinaceous and non-ubiquitylated cargoes are also selectively degraded by this pathway. This ubiquitin-independent selective autophagic pathway also involves receptor and/or adaptor proteins linking the cargo to the autophagic machinery. Some of these receptor/adaptor proteins including accessory autophagy-related (Atg and non-Atg proteins have been described in yeast and animal cells but not yet in plants. In this review we discuss the ubiquitin-independent cargo selection mechanisms in selective autophagy degradation of organelles and macromolecules and speculate on potential plant receptor/adaptor proteins.

  12. Faces from the web: automatic selection and composition of media for casual screen consumption and printed artwork

    Science.gov (United States)

    Cheatle, Phil; Greig, Darryl; Slatter, David

    2010-02-01

    Web image search engines facilitate the production of image sets in which faces appear. Many people enjoy producing and sharing media collections of this type and generating new images or video experiences. Skilled practitioners produce visually appealing artifacts from such collections but few users have the time or creative ability to do so. The problem is to automatically create an image or ambient experience which sustains interest. A full solution requires agreements with copyright holders and input from graphics designers. We address the underlying technical problems of extraction and composition. We describe an automatic system that identifies regions containing human faces in each image of an image set resulting from a web search. The face regions are composed into dynamically synthesized multilayer graphical backgrounds. The aesthetic aspects of the composition are controlled by active templates. These aspects include face size and positioning but also face identity and number of faces in a group. The output structure is multi layer supporting both the generation of static images and video consisting of transitions between the compositions.

  13. THE SDSS-III BARYON OSCILLATION SPECTROSCOPIC SURVEY: QUASAR TARGET SELECTION FOR DATA RELEASE NINE

    Energy Technology Data Exchange (ETDEWEB)

    Ross, Nicholas P.; Kirkpatrick, Jessica A.; Carithers, William C.; Ho, Shirley [Lawrence Berkeley National Laboratory, 1 Cyclotron Road, Berkeley, CA 94720 (United States); Myers, Adam D. [Department of Astronomy, MC-221, University of Illinois, 1002 West Green Street, Urbana, IL 61801 (United States); Sheldon, Erin S. [Brookhaven National Laboratory, Blgd 510, Upton, NY 11375 (United States); Yeche, Christophe; Aubourg, Eric [CEA, Centre de Saclay, IRFU, 91191 Gif-sur-Yvette (France); Strauss, Michael A.; Lee, Khee-Gan [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Bovy, Jo; Blanton, Michael R.; Hogg, David W. [Center for Cosmology and Particle Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Richards, Gordon T. [Department of Physics, Drexel University, 3141 Chestnut Street, Philadelphia, PA 19104 (United States); Brandt, W. N. [Department of Astronomy and Astrophysics, The Pennsylvania State University, 525 Davey Laboratory, University Park, PA 16802 (United States); Croft, Rupert A. C. [Bruce and Astrid McWilliams Center for Cosmology, Carnegie Mellon University, Pittsburgh, PA 15213 (United States); Da Silva, Robert [Department of Astronomy and Astrophysics, University of California, Santa Cruz, Santa Cruz, CA 95064 (United States); Dawson, Kyle [Department of Physics and Astronomy, University of Utah, UT (United States); Eisenstein, Daniel J. [Steward Observatory, 933 North Cherry Avenue, Tucson, AZ 85721 (United States); Hennawi, Joseph F., E-mail: npross@lbl.gov [Max-Planck-Institut fuer Astronomie, Konigstuhl 17, 69117 Heidelberg (Germany); and others

    2012-03-01

    The SDSS-III Baryon Oscillation Spectroscopic Survey (BOSS), a five-year spectroscopic survey of 10,000 deg{sup 2}, achieved first light in late 2009. One of the key goals of BOSS is to measure the signature of baryon acoustic oscillations (BAOs) in the distribution of Ly{alpha} absorption from the spectra of a sample of {approx}150,000 z > 2.2 quasars. Along with measuring the angular diameter distance at z Almost-Equal-To 2.5, BOSS will provide the first direct measurement of the expansion rate of the universe at z > 2. One of the biggest challenges in achieving this goal is an efficient target selection algorithm for quasars in the redshift range 2.2 < z < 3.5, where their colors tend to overlap those of the far more numerous stars. During the first year of the BOSS survey, quasar target selection (QTS) methods were developed and tested to meet the requirement of delivering at least 15 quasars deg{sup -2} in this redshift range, with a goal of 20 out of 40 targets deg{sup -2} allocated to the quasar survey. To achieve these surface densities, the magnitude limit of the quasar targets was set at g {<=} 22.0 or r {<=} 21.85. While detection of the BAO signature in the distribution of Ly{alpha} absorption in quasar spectra does not require a uniform target selection algorithm, many other astrophysical studies do. We have therefore defined a uniformly selected subsample of 20 targets deg{sup -2}, for which the selection efficiency is just over 50% ({approx}10 z > 2.20 quasars deg{sup -2}). This 'CORE' subsample will be fixed for Years Two through Five of the survey. For the remaining 20 targets deg{sup -2}, we will continue to develop improved selection techniques, including the use of additional data sets beyond the Sloan Digital Sky Survey (SDSS) imaging data. In this paper, we describe the evolution and implementation of the BOSS QTS algorithms during the first two years of BOSS operations (through 2011 July), in support of the science investigations

  14. Target Selection and Deselection at the Berkeley StructuralGenomics Center

    Energy Technology Data Exchange (ETDEWEB)

    Chandonia, John-Marc; Kim, Sung-Hou; Brenner, Steven E.

    2005-03-22

    At the Berkeley Structural Genomics Center (BSGC), our goalis to obtain a near-complete structural complement of proteins in theminimal organisms Mycoplasma genitalium and M. pneumoniae, two closelyrelated pathogens. Current targets for structure determination have beenselected in six major stages, starting with those predicted to be mosttractable to high throughput study and likely to yield new structuralinformation. We report on the process used to select these proteins, aswell as our target deselection procedure. Target deselection reducesexperimental effort by eliminating targets similar to those recentlysolved by the structural biology community or other centers. We measurethe impact of the 69 structures solved at the BSGC as of July 2004 onstructure prediction coverage of the M. pneumoniae and M. genitaliumproteomes. The number of Mycoplasma proteins for which thefold couldfirst be reliably assigned based on structures solved at the BSGC (24 M.pneumoniae and 21 M. genitalium) is approximately 25 percent of the totalresulting from work at all structural genomics centers and the worldwidestructural biology community (94 M. pneumoniae and 86M. genitalium)during the same period. As the number of structures contributed by theBSGC during that period is less than 1 percent of the total worldwideoutput, the benefits of a focused target selection strategy are apparent.If the structures of all current targets were solved, the percentage ofM. pneumoniae proteins for which folds could be reliably assigned wouldincrease from approximately 57 percent (391 of 687) at present to around80 percent (550 of 687), and the percentage of the proteome that could beaccurately modeled would increase from around 37 percent (254 of 687) toabout 64 percent (438 of 687). In M. genitalium, the percentage of theproteome that could be structurally annotated based on structures of ourremaining targets would rise from 72 percent (348 of 486) to around 76percent (371 of 486), with the

  15. Implications of structural genomics target selection strategies: Pfam5000, whole genome, and random approaches

    Energy Technology Data Exchange (ETDEWEB)

    Chandonia, John-Marc; Brenner, Steven E.

    2004-07-14

    The structural genomics project is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy which is medically and biologically relevant, of good value, and tractable. As an option to consider, we present the Pfam5000 strategy, which involves selecting the 5000 most important families from the Pfam database as sources for targets. We compare the Pfam5000 strategy to several other proposed strategies that would require similar numbers of targets. These include including complete solution of several small to moderately sized bacterial proteomes, partial coverage of the human proteome, and random selection of approximately 5000 targets from sequenced genomes. We measure the impact that successful implementation of these strategies would have upon structural interpretation of the proteins in Swiss-Prot, TrEMBL, and 131 complete proteomes (including 10 of eukaryotes) from the Proteome Analysis database at EBI. Solving the structures of proteins from the 5000 largest Pfam families would allow accurate fold assignment for approximately 68 percent of all prokaryotic proteins (covering 59 percent of residues) and 61 percent of eukaryotic proteins (40 percent of residues). More fine-grained coverage which would allow accurate modeling of these proteins would require an order of magnitude more targets. The Pfam5000 strategy may be modified in several ways, for example to focus on larger families, bacterial sequences, or eukaryotic sequences; as long as secondary consideration is given to large families within Pfam, coverage results vary only slightly. In contrast, focusing structural genomics on a single tractable genome would have only a limited impact in structural knowledge of other proteomes: a significant fraction (about 30-40 percent of the proteins, and 40-60 percent of the residues) of each proteome is classified in small

  16. Autocrine-Based Selection of Drugs That Target Ion Channels from Combinatorial Venom Peptide Libraries.

    Science.gov (United States)

    Zhang, Hongkai; Du, Mingjuan; Xie, Jia; Liu, Xiao; Sun, Jingying; Wang, Wei; Xin, Xiu; Possani, Lourival D; Yea, Kyungmoo; Lerner, Richard A

    2016-08-01

    Animal venoms represent a rich source of pharmacologically active peptides that interact with ion channels. However, a challenge to discovering drugs remains because of the slow pace at which venom peptides are discovered and refined. An efficient autocrine-based high-throughput selection system was developed to discover and refine venom peptides that target ion channels. The utility of this system was demonstrated by the discovery of novel Kv1.3 channel blockers from a natural venom peptide library that was formatted for autocrine-based selection. We also engineered a Kv1.3 blocker peptide (ShK) derived from sea anemone to generate a subtype-selective Kv1.3 blocker with a long half-life in vivo. PMID:27197631

  17. PI3K isoform-selective inhibitors: next-generation targeted cancer therapies.

    Science.gov (United States)

    Wang, Xiang; Ding, Jian; Meng, Ling-hua

    2015-10-01

    The pivotal roles of phosphatidylinositol 3-kinases (PI3Ks) in human cancers have inspired active development of small molecules to inhibit these lipid kinases. However, the first-generation pan-PI3K and dual-PI3K/mTOR inhibitors have encountered problems in clinical trials, with limited efficacies as a monotherapeutic agent as well as a relatively high rate of side effects. It is increasingly recognized that different PI3K isoforms play non-redundant roles in particular tumor types, which has prompted the development of isoform-selective inhibitors for pre-selected patients with the aim for improving efficacy while decreasing undesirable side effects. The success of PI3K isoform-selective inhibitors is represented by CAL101 (Idelalisib), a first-in-class PI3Kδ-selective small-molecule inhibitor that has been approved by the FDA for the treatment of chronic lymphocytic leukemia, indolent B-cell non-Hodgkin's lymphoma and relapsed small lymphocytic lymphoma. Inhibitors targeting other PI3K isoforms are also being extensively developed. This review focuses on the recent progress in development of PI3K isoform-selective inhibitors for cancer therapy. A deeper understanding of the action modes of novel PI3K isoform-selective inhibitors will provide valuable information to further validate the concept of targeting specific PI3K isoforms, while the identification of biomarkers to stratify patients who are likely to benefit from the therapy will be essential for the success of these agents. PMID:26364801

  18. Targeted and random bacterial gene disruption using a group II intron (targetron) vector containing a retrotransposition-activated selectable marker

    OpenAIRE

    Zhong, Jin; Karberg, Michael; Lambowitz, Alan M.

    2003-01-01

    Mobile group II introns have been used to develop a novel class of gene targeting vectors, targetrons, which employ base pairing for DNA target recognition and can thus be programmed to insert into any desired target DNA. Here, we have developed a targetron containing a retrotransposition-activated selectable marker (RAM), which enables one-step bacterial gene disruption at near 100% efficiency after selection. The targetron can be generated via PCR without cloning, and after intron integrati...

  19. Salinomycin induces selective cytotoxicity to MCF-7 mammosphere cells through targeting the Hedgehog signaling pathway.

    Science.gov (United States)

    Fu, Ying-Zi; Yan, Yuan-Yuan; He, Miao; Xiao, Qing-Huan; Yao, Wei-Fan; Zhao, Lin; Wu, Hui-Zhe; Yu, Zhao-Jin; Zhou, Ming-Yi; Lv, Mu-Tian; Zhang, Shan-Shan; Chen, Jian-Jun; Wei, Min-Jie

    2016-02-01

    Breast cancer stem cells (BCSCs) are believed to be responsible for tumor chemoresistance, recurrence, and metastasis formation. Salinomycin (SAL), a carboxylic polyether ionophore, has been reported to act as a selective breast CSC inhibitor. However, the molecular mechanisms underlying SAL-induced cytotoxicity on BCSCs remain unclear. The Hedgehog (Hh) signaling pathway plays an important role in CSC maintenance and carcinogenesis. Here, we investigated whether SAL induces cytotoxicity on BCSCs through targeting Hh pathway. In the present study, we cultured breast cancer MCF-7 cells in suspension in serum-free medium to obtain breast CSC-enriched MCF-7 mammospheres (MCF-7 MS). MCF-7 MS cells possessed typical BCSC properties, such as CD44+CD24-/low phenotype, high expression of OCT4 (a stem cell marker), increased colony-forming ability, strong migration and invasion capabilities, differentiation potential, and strong tumorigenicity in xenografted mice. SAL exhibited selective cytotoxicity to MCF-7 MS cells relative to MCF-7 cells. The Hh pathway was highly activated in BCSC-enriched MCF-7 MS cells and SAL inhibited Hh signaling activation by downregulating the expression of critical components of the Hh pathway such as PTCH, SMO, Gli1, and Gli2, and subsequently repressing the expression of their essential downstream targets including C-myc, Bcl-2, and Snail (but not cyclin D1). Conversely, Shh-induced Hh signaling activation could largely reverse SAL-mediated inhibitory effects. These findings suggest that SAL-induced selective cytotoxicity against MCF-7 MS cells is associated with the inhibition of Hh signaling activation and the expression of downstream targets and the Hh pathway is an important player and a possible drug target in the pathogenesis of BCSCs. PMID:26718029

  20. Selective targeting of melanoma by PEG-masked protein-based multifunctional nanoparticles

    Directory of Open Access Journals (Sweden)

    Vannucci L

    2012-03-01

    techniques, and assayed for selective melanoma-targeting in vitro and in vivo.Results: Our HFt-based nanoparticle constructs functionalized with the α-melanocyte-stimulating hormone peptide moiety and polyethylene glycol molecules were specifically taken up by melanoma cells but not by other cancer cell types in vitro. Moreover, experiments in melanoma-bearing mice indicate that these constructs have an excellent tumor-targeting profile and a long circulation time in vivo.Conclusion: By masking human HFt with polyethylene glycol and targeting it with an α-melanocyte-stimulating hormone peptide, we developed an HFt-based melanoma-targeting nanoplatform for application in melanoma diagnosis and treatment. These results could be of general interest, because the same strategy can be exploited to develop ad hoc nanoplatforms for specific delivery towards any cell/tissue type for which a suitable targeting moiety is available.Keywords: multifunctional nanoparticles, ferritin, nanoplatform, cancer-targeting, melanoma

  1. The contribution of the major planet search surveys to EChO target selection

    Science.gov (United States)

    Micela, Giuseppina; Bakos, Gáspár Á.; Lopez-Morales, Mercedes; Maxted, Pierre F. L.; Pagano, Isabella; Sozzetti, Alessandro; Wheatley, Peter J.

    2015-12-01

    The EChO core science will be based on a three tier survey, each with increasing sensitivity, in order to study the population of exo-planets from super-Earths to Jupiter-like planets, in the very hot to temperate zones (temperatures of 300 K - 3000 K) of F to M-type host stars. To achieve a meaningful outcome, an accurate selection of the target sample is needed. In this paper we analyse the targets, suitable for EChO observations, expected to result from a sample of present and forthcoming detection surveys. Present day discovered exoplanets are sufficient to provide a large and diverse sample. However we expect that results from ongoing and planned surveys, aimed at identifying new planets, will increase the sample of smaller planets allowing us to optimize the EChO sample selection. The analysis of the expected yields of a representative set of those surveys both from ground and space shows that they will be able to provide a large number of targets, covering an ample range of planetary and stellar parameters, fitting the EChO capabilities.

  2. Combined use of automatic tube voltage selection and current modulation with iterative reconstruction for CT evaluation of small hypervascular hepatocellular carcinomas: Effect on lesion conspicuity and image quality

    International Nuclear Information System (INIS)

    To assess the lesion conspicuity and image quality in CT evaluation of small (< or = 3 cm) hepatocellular carcinomas (HCCs) using automatic tube voltage selection (ATVS) and automatic tube current modulation (ATCM) with or without iterative reconstruction. One hundred and five patients with 123 HCC lesions were included. Fifty-seven patients were scanned using both ATVS and ATCM and images were reconstructed using either filtered back-projection (FBP) (group A1) or sinogram-affirmed iterative reconstruction (SAFIRE) (group A2). Forty-eight patients were imaged using only ATCM, with a fixed tube potential of 120 kVp and FBP reconstruction (group B). Quantitative parameters (image noise in Hounsfield unit and contrast-to-noise ratio of the aorta, the liver, and the hepatic tumors) and qualitative visual parameters (image noise, overall image quality, and lesion conspicuity as graded on a 5-point scale) were compared among the groups. Group A2 scanned with the automatically chosen 80 kVp and 100 kVp tube voltages ranked the best in lesion conspicuity and subjective and objective image quality (p values ranging from < 0.001 to 0.004) among the three groups, except for overall image quality between group A2 and group B (p = 0.022). Group A1 showed higher image noise (p = 0.005) but similar lesion conspicuity and overall image quality as compared with group B. The radiation dose in group A was 19% lower than that in group B (p = 0.022). CT scanning with combined use of ATVS and ATCM and image reconstruction with SAFIRE algorithm provides higher lesion conspicuity and better image quality for evaluating small hepatic HCCs with radiation dose reduction.

  3. The SDSS-IV extended Baryonic Oscillation Spectroscopic Survey: Quasar Target Selection

    CERN Document Server

    Myers, Adam D; Prakash, Abhishek; Pâris, Isabelle; Yeche, Christophe; Dawson, Kyle S; Bovy, Jo; Lang, Dustin; Schlegel, David J; Newman, Jeffrey A; Petitjean, Patrick; Kneib, Jean Paul; Laurent, Pierre; Percival, Will J; Ross, Ashley J; Seo, Hee-Jong; Tinker, Jeremy L; Armengaud, Eric; Brownstein, Joel; Burtin, Etienne; Cai, Zheng; Comparat, Johan; Kasliwal, Mansi; Kulkarni, Shrinivas R; Laher, Russ; Levitan, David; McBride, Cameron K; McGreer, Ian D; Miller, Adam A; Nugent, Peter; Ofek, Eran; Rossi, Graziano; Ruan, John; Schneider, Donald P; Sesar, Branimir; Streblyanska, Alina; Surace, Jason

    2015-01-01

    As part of the SDSS-IV the extended Baryon Oscillation Spectroscopic Survey (eBOSS) will perform measurements of the cosmological distance scale via application of the Baryon Acoustic Oscillation (BAO) method to samples of quasars and galaxies. Quasar surveys are particularly useful in the BAO context as they can trace extremely large volumes back to moderately high redshift. eBOSS will adopt two approaches to target quasars over a 7500 sq. deg. area. First, z > 2.1 quasars will be targeted to improve BAO measurements in the Lyman-Alpha Forest. Second, a homogeneously selected "CORE" sample of quasars at 0.9 2.1 quasars. A supplemental selection based on variability of quasars in multi-epoch imaging from the Palomar Transient Factory should recover an additional ~3-4 per sq. deg. z > 2.1 quasars to g 500,000 new spectroscopically confirmed quasars and > 500,000 uniformly selected spectroscopically confirmed 0.9 < z < 2.2 quasars. At the conclusion of SDSS-IV, the SDSS will have provided unique spectra...

  4. Selective cell targeting and lineage tracing of human induced pluripotent stem cells using recombinant avian retroviruses.

    Science.gov (United States)

    Hildebrand, Laura; Seemann, Petra; Kurtz, Andreas; Hecht, Jochen; Contzen, Jörg; Gossen, Manfred; Stachelscheid, Harald

    2015-12-01

    Human induced pluripotent stem cells (hiPSC) differentiate into multiple cell types. Selective cell targeting is often needed for analyzing gene function by overexpressing proteins in a distinct population of hiPSC-derived cell types and for monitoring cell fate in response to stimuli. However, to date, this has not been possible, as commonly used viruses enter the hiPSC via ubiquitously expressed receptors. Here, we report for the first time the application of a heterologous avian receptor, the tumor virus receptor A (TVA), to selectively transduce TVA(+) cells in a mixed cell population. Expression of the TVA surface receptor via genetic engineering renders cells susceptible for infection by avian leucosis virus (ALV). We generated hiPSC lines with this stably integrated, ectopic TVA receptor gene that expressed the receptor while retaining pluripotency. The undifferentiated hiPSC(TVA+) as well as their differentiating progeny could be infected by recombinant ALV (so-called RCAS virus) with high efficiency. Due to incomplete receptor blocking, even sequential infection of differentiating or undifferentiated TVA(+) cells was possible. In conclusion, the TVA/RCAS system provides an efficient and gentle gene transfer system for hiPSC and extends our possibilities for selective cell targeting and lineage tracing studies. PMID:26109426

  5. Selection of Phage Display Peptides Targeting Human Pluripotent Stem Cell-Derived Progenitor Cell Lines.

    Science.gov (United States)

    Bignone, Paola A; Krupa, Rachel A; West, Michael D; Larocca, David

    2016-01-01

    The ability of human pluripotent stem cells (hPS) to both self-renew and differentiate into virtually any cell type makes them a promising source of cells for cell-based regenerative therapies. However, stem cell identity, purity, and scalability remain formidable challenges that need to be overcome for translation of pluripotent stem cell research into clinical applications. Directed differentiation from hPS cells is inefficient and residual contamination with pluripotent cells that have the potential to form tumors remains problematic. The derivation of scalable (self-renewing) embryonic progenitor stem cell lines offers a solution because they are well defined and clonally pure. Clonally pure progenitor stem cell lines also provide a means for identifying cell surface targeting reagents that are useful for identification, tracking, and repeated derivation of the corresponding progenitor stem cell types from additional hPS cell sources. Such stem cell targeting reagents can then be applied to the manufacture of genetically diverse banks of human embryonic progenitor cell lines for drug screening, disease modeling, and cell therapy. Here we present methods to identify human embryonic progenitor stem cell targeting peptides by selection of phage display libraries on clonal embryonic progenitor cell lines and demonstrate their use for targeting quantum dots (Qdots) for stem cell labeling. PMID:25410289

  6. Selection and delineation of target volumes in head and neck tumors: beyond ICRU definition

    International Nuclear Information System (INIS)

    Improvement in irradiation techniques, which allows dose distributions sculpting around volumes of very complex shapes, has revealed the limitations in selection and delineation of target volumes. The use of functional imaging (PET, fMRI) in addition to anatomic imaging, will probably bring an extra level of complexity to this issue. In particular, the use of specific markers to visualize biological pathways known to influence response to ionizing radiation (e.g. hypoxia, proliferation) could lead to the delineation of sub-target volumes for delivering an extra boost dose. Such concept of Image-Guided Radiation Therapy still need to be tested in experimental models and in well defined clinical situations before its use in a routine clinical set-up. (author)

  7. Masitinib (AB1010, a potent and selective tyrosine kinase inhibitor targeting KIT.

    Directory of Open Access Journals (Sweden)

    Patrice Dubreuil

    Full Text Available BACKGROUND: The stem cell factor receptor, KIT, is a target for the treatment of cancer, mastocytosis, and inflammatory diseases. Here, we characterise the in vitro and in vivo profiles of masitinib (AB1010, a novel phenylaminothiazole-type tyrosine kinase inhibitor that targets KIT. METHODOLOGY/PRINCIPAL FINDINGS: In vitro, masitinib had greater activity and selectivity against KIT than imatinib, inhibiting recombinant human wild-type KIT with an half inhibitory concentration (IC(50 of 200+/-40 nM and blocking stem cell factor-induced proliferation and KIT tyrosine phosphorylation with an IC(50 of 150+/-80 nM in Ba/F3 cells expressing human or mouse wild-type KIT. Masitinib also potently inhibited recombinant PDGFR and the intracellular kinase Lyn, and to a lesser extent, fibroblast growth factor receptor 3. In contrast, masitinib demonstrated weak inhibition of ABL and c-Fms and was inactive against a variety of other tyrosine and serine/threonine kinases. This highly selective nature of masitinib suggests that it will exhibit a better safety profile than other tyrosine kinase inhibitors; indeed, masitinib-induced cardiotoxicity or genotoxicity has not been observed in animal studies. Molecular modelling and kinetic analysis suggest a different mode of binding than imatinib, and masitinib more strongly inhibited degranulation, cytokine production, and bone marrow mast cell migration than imatinib. Furthermore, masitinib potently inhibited human and murine KIT with activating mutations in the juxtamembrane domain. In vivo, masitinib blocked tumour growth in mice with subcutaneous grafts of Ba/F3 cells expressing a juxtamembrane KIT mutant. CONCLUSIONS: Masitinib is a potent and selective tyrosine kinase inhibitor targeting KIT that is active, orally bioavailable in vivo, and has low toxicity.

  8. Pancratistatin selectively targets cancer cell mitochondria and reduces growth of human colon tumor xenografts.

    Science.gov (United States)

    Griffin, Carly; Karnik, Aditya; McNulty, James; Pandey, Siyaram

    2011-01-01

    The naturally occurring Amaryllidaceae alkaloid pancratistatin exhibits potent apoptotic activity against a large panel of cancer cells lines and has an insignificant effect on noncancerous cell lines, although with an elusive cellular target. Many current chemotherapeutics induce apoptosis via genotoxic mechanisms and thus have low selectivity. The observed selectivity of pancratistatin for cancer cells promoted us to consider the hypothesis that this alkaloid targets cancer cell mitochondria rather than DNA or its replicative machinery. In this study, we report that pancratistatin decreased mitochondrial membrane potential and induced apoptotic nuclear morphology in p53-mutant (HT-29) and wild-type p53 (HCT116) colorectal carcinoma cell lines, but not in noncancerous colon fibroblast (CCD-18Co) cells. Interestingly, pancratistatin was found to be ineffective against mtDNA-depleted (ρ(0)) cancer cells. Moreover, pancratistatin induced cell death in a manner independent of Bax and caspase activation, and did not alter β-tubulin polymerization rate nor cause double-stranded DNA breaks. For the first time we report the efficacy of pancratistatin in vivo against human colorectal adenocarcinoma xenografts. Intratumor administration of pancratistatin (3 mg/kg) caused significant reduction in the growth of subcutaneous HT-29 tumors in Nu/Nu mice (n = 6), with no apparent toxicity to the liver or kidneys as indicated by histopathologic analysis and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling. Altogether, this work suggests that pancratistatin may be a novel mitochondria-targeting compound that selectively induces apoptosis in cancer cells and significantly reduces tumor growth. PMID:21220492

  9. Entry mode choice and target firm selection: private and collective incentive analysis

    OpenAIRE

    Zhao, Kai

    2012-01-01

    The purpose of this paper is to formalize the choices of market entry strategy (Export Vs Greenfield investment Vs Cross border M&A) and the target selection (Acquisition of high-productivity firm or low-productivity one) for a foreign firm, and to delineate the relationship between foreign firm’s incentive and host government’s intention from an Industrial Organization (IO) perspective. It is found that cross border M&A is always the most profitable entry mode under both greenfield investmen...

  10. Advancing the sensitivity of selected reaction monitoring-based targeted quantitative proteomics

    OpenAIRE

    Shi, Tujin; Su, Dian; Liu, Tao; Tang, Keqi; Camp, David G; Qian, Wei-Jun; Smith, Richard D.

    2012-01-01

    Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the low ng/mL to pg/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in...

  11. Rapid and targeted introgression of genes into popular wheat cultivars using marker-assisted background selection.

    Directory of Open Access Journals (Sweden)

    Harpinder S Randhawa

    Full Text Available A marker-assisted background selection (MABS-based gene introgression approach in wheat (Triticum aestivum L. was optimized, where 97% or more of a recurrent parent genome (RPG can be recovered in just two backcross (BC generations. A four-step MABS method was developed based on 'Plabsim' computer simulations and wheat genome structure information. During empirical optimization of this method, double recombinants around the target gene were selected in a step-wise fashion during the two BC cycles followed by selection for recurrent parent genotype on non-carrier chromosomes. The average spacing between carrier chromosome markers was <4 cM. For non-carrier chromosome markers that flanked each of the 48 wheat gene-rich regions, this distance was approximately 12 cM. Employed to introgress seedling stripe rust (Puccinia striiformis f. sp. tritici resistance gene Yr15 into the spring wheat cultivar 'Zak', marker analysis of 2,187 backcross-derived progeny resulted in the recovery of a BC(2F(2ratio3 plant with 97% of the recurrent parent genome. In contrast, only 82% of the recurrent parent genome was recovered in phenotypically selected BC(4F(7 plants developed without MABS. Field evaluation results from 17 locations indicated that the MABS-derived line was either equal or superior to the recurrent parent for the tested agronomic characteristics. Based on these results, MABS is recommended as a strategy for rapidly introgressing a targeted gene into a wheat genotype in just two backcross generations while recovering 97% or more of the recurrent parent genotype.

  12. Selection and characterization of Anticalins targeting human prostate-specific membrane antigen (PSMA).

    Science.gov (United States)

    Barinka, Cyril; Ptacek, Jakub; Richter, Antonia; Novakova, Zora; Morath, Volker; Skerra, Arne

    2016-03-01

    Although prostate carcinoma (PCa) is by far the most commonly diagnosed neoplasia in men, corresponding diagnostic and therapeutic modalities have limited efficacy at present. Anticalins comprise a novel class of binding proteins based on a non-immunoglobulin scaffold that can be engineered to specifically address molecular targets of interest. Here we report the selection and characterization of Anticalins that recognize human prostate-specific membrane antigen (PSMA), a membrane-tethered metallopeptidase constituting a disease-related target for imaging and therapy of PCa as well as solid malignancies in general. We used a randomized lipocalin library based on the human lipocalin 2 (Lcn2) scaffold together with phage display and ELISA screening to select PSMA-specific variants. Five Anticalin candidates from the original panning were expressed in Escherichia coli as soluble monomeric proteins, revealing affinities toward PSMA down to the low nanomolar range. Binding characteristics of the most promising candidate were further improved via affinity maturation by applying error-prone PCR followed by selection via phage display as well as bacterial surface display under more stringent conditions. In BIAcore measurements, the dissociation constant of the best Anticalin was determined as ∼500 pM, with a substantially improved dissociation rate compared with the first-generation candidate. Finally, immunofluorescence microscopy revealed specific staining of PSMA-positive tumor cell lines while flow cytometric analysis confirmed the ability of the selected Anticalins to detect PSMA on live cells. Taken together, Anticalins resulting from this study offer a viable alternative to antibody-based PSMA binders for biomedical applications, including in vivo imaging of PCa or neovasculature of solid tumors. PMID:26802163

  13. Selective pressures for accurate altruism targeting: evidence from digital evolution for difficult-to-test aspects of inclusive fitness theory.

    Science.gov (United States)

    Clune, Jeff; Goldsby, Heather J; Ofria, Charles; Pennock, Robert T

    2011-03-01

    Inclusive fitness theory predicts that natural selection will favour altruist genes that are more accurate in targeting altruism only to copies of themselves. In this paper, we provide evidence from digital evolution in support of this prediction by competing multiple altruist-targeting mechanisms that vary in their accuracy in determining whether a potential target for altruism carries a copy of the altruist gene. We compete altruism-targeting mechanisms based on (i) kinship (kin targeting), (ii) genetic similarity at a level greater than that expected of kin (similarity targeting), and (iii) perfect knowledge of the presence of an altruist gene (green beard targeting). Natural selection always favoured the most accurate targeting mechanism available. Our investigations also revealed that evolution did not increase the altruism level when all green beard altruists used the same phenotypic marker. The green beard altruism levels stably increased only when mutations that changed the altruism level also changed the marker (e.g. beard colour), such that beard colour reliably indicated the altruism level. For kin- and similarity-targeting mechanisms, we found that evolution was able to stably adjust altruism levels. Our results confirm that natural selection favours altruist genes that are increasingly accurate in targeting altruism to only their copies. Our work also emphasizes that the concept of targeting accuracy must include both the presence of an altruist gene and the level of altruism it produces. PMID:20843843

  14. The SDSS-IV Extended Baryon Oscillation Spectroscopic Survey: Quasar Target Selection

    Science.gov (United States)

    Myers, Adam D.; Palanque-Delabrouille, Nathalie; Prakash, Abhishek; Pâris, Isabelle; Yeche, Christophe; Dawson, Kyle S.; Bovy, Jo; Lang, Dustin; Schlegel, David J.; Newman, Jeffrey A.; Petitjean, Patrick; Kneib, Jean-Paul; Laurent, Pierre; Percival, Will J.; Ross, Ashley J.; Seo, Hee-Jong; Tinker, Jeremy L.; Armengaud, Eric; Brownstein, Joel; Burtin, Etienne; Cai, Zheng; Comparat, Johan; Kasliwal, Mansi; Kulkarni, Shrinivas R.; Laher, Russ; Levitan, David; McBride, Cameron K.; McGreer, Ian D.; Miller, Adam A.; Nugent, Peter; Ofek, Eran; Rossi, Graziano; Ruan, John; Schneider, Donald P.; Sesar, Branimir; Streblyanska, Alina; Surace, Jason

    2015-12-01

    As part of the Sloan Digital Sky Survey (SDSS) IV the extended Baryon Oscillation Spectroscopic Survey (eBOSS) will improve measurements of the cosmological distance scale by applying the Baryon Acoustic Oscillation (BAO) method to quasar samples. eBOSS will adopt two approaches to target quasars over 7500 deg2. First, a “CORE” quasar sample will combine the optical selection in ugriz using a likelihood-based routine called XDQSOz, with a mid-IR-optical color cut. eBOSS CORE selection (to g 2.1 quasars. Second, a selection based on variability in multi-epoch imaging from the Palomar Transient Factory should recover an additional ˜3-4 deg-2z > 2.1 quasars to g sample should thus be sufficiently dense and homogeneous over 0.9 2.1 will be used to improve BAO measurements in the Lyα Forest. Beyond its key cosmological goals, eBOSS should be the next-generation quasar survey, comprising >500,000 new quasars and >500,000 uniformly selected spectroscopically confirmed 0.9 < z < 2.2 quasars. At the conclusion of eBOSS, the SDSS will have provided unique spectra for more than 800,000 quasars.

  15. Criteria for selection of target materials and design of high-efficiency-release targets for radioactive ion beam generation

    CERN Document Server

    Alton, G D; Liu, Y

    1999-01-01

    In this report, we define criteria for choosing target materials and for designing, mechanically stable, short-diffusion-length, highly permeable targets for generation of high-intensity radioactive ion beams (RIBs) for use at nuclear physics and astrophysics research facilities based on the ISOL principle. In addition, lists of refractory target materials are provided and examples are given of a number of successful targets, based on these criteria, that have been fabricated and tested for use at the Holifield Radioactive Ion Beam Facility (HRIBF).

  16. 3D models automatic reconstruction of selected close range objects. (Polish Title: Automatyczna rekonstrukcja modeli 3D małych obiektów bliskiego zasiegu)

    Science.gov (United States)

    Zaweiska, D.

    2013-12-01

    Reconstruction of three-dimensional, realistic models of objects from digital images has been the topic of research in many areas of science for many years. This development is stimulated by new technologies and tools, which appeared recently, such as digital photography, laser scanners, increase in the equipment efficiency and Internet. The objective of this paper is to present results of automatic modeling of selected close range objects, with the use of digital photographs acquired by the Hasselblad H4D50 camera. The author's software tool was utilized for calculations; it performs successive stages of the 3D model creation. The modeling process was presented as the complete process which starts from acquisition of images and which is completed by creation of a photorealistic 3D model in the same software environment. Experiments were performed for selected close range objects, with appropriately arranged image geometry, creating a ring around the measured object. The Area Base Matching (CC/LSM) method, the RANSAC algorithm, with the use of tensor calculus, were utilized form automatic matching of points detected with the SUSAN algorithm. Reconstruction of the surface of model generation is one of the important stages of 3D modeling. Reconstruction of precise surfaces, performed on the basis of a non-organized cloud of points, acquired from automatic processing of digital images, is a difficult task, which has not been finally solved. Creation of poly-angular models, which may meet high requirements concerning modeling and visualization is required in many applications. The polynomial method is usually the best way to precise representation of measurement results, and, at the same time, to achieving the optimum description of the surface. Three algorithm were tested: the volumetric method (VCG), the Poisson method and the Ball pivoting method. Those methods are mostly applied to modeling of uniform grids of points. Results of experiments proved that incorrect

  17. Update on the Pfam5000 Strategy for Selection of StructuralGenomics Targets

    Energy Technology Data Exchange (ETDEWEB)

    Chandonia, John-Marc; Brenner, Steven E.

    2005-06-27

    Structural Genomics is an international effort to determine the three-dimensional shapes of all important biological macromolecules, with a primary focus on proteins. Target proteins should be selected according to a strategy that is medically and biologically relevant, of good financial value, and tractable. In 2003, we presented the ''Pfam5000'' strategy, which involves selecting the 5,000 most important families from the Pfam database as sources for targets. In this update, we show that although both the Pfam database and the number of sequenced genomes have increased in size, the expected benefits of the Pfam5000 strategy have not changed substantially. Solving the structures of proteins from the 5,000 largest Pfam families would allow accurate fold assignment for approximately 65 percent of all prokaryotic proteins (covering 54 percent of residues) and 63 percent of eukaryotic proteins (42 percent of residues). Fewer than 2,300 of the largest families on this list remain to be solved, making the project feasible in the next five years given the expected throughput to be achieved in the production phase of the Protein Structure Initiative.

  18. Does Angling Technique Selectively Target Fishes Based on Their Behavioural Type?

    Directory of Open Access Journals (Sweden)

    Alexander D M Wilson

    Full Text Available Recently, there has been growing recognition that fish harvesting practices can have important impacts on the phenotypic distributions and diversity of natural populations through a phenomenon known as fisheries-induced evolution. Here we experimentally show that two common recreational angling techniques (active crank baits versus passive soft plastics differentially target wild largemouth bass (Micropterus salmoides and rock bass (Ambloplites rupestris based on variation in their behavioural tendencies. Fish were first angled in the wild using both techniques and then brought back to the laboratory and tested for individual-level differences in common estimates of personality (refuge emergence, flight-initiation-distance, latency-to-recapture and with a net, and general activity in an in-lake experimental arena. We found that different angling techniques appear to selectively target these species based on their boldness (as characterized by refuge emergence, a standard measure of boldness in fishes but not other assays of personality. We also observed that body size was independently a significant predictor of personality in both species, though this varied between traits and species. Our results suggest a context-dependency for vulnerability to capture relative to behaviour in these fish species. Ascertaining the selective pressures angling practices exert on natural populations is an important area of fisheries research with significant implications for ecology, evolution, and resource management.

  19. Selection of flowing liquid lead target structural materials for accelerator driven transmutation applications

    International Nuclear Information System (INIS)

    The beam entry window and container for a liquid lead spallation target will be exposed to high fluxes of protons and neutrons that are both higher in magnitude and energy than have been experienced in proton accelerators and fission reactors, as well as in a corrosive environment. The structural material of the target should have a good compatibility with liquid lead, a sufficient mechanical strength at elevated temperatures, a good performance under an intense irradiation environment, and a low neutron absorption cross section; these factors have been used to rank the applicability of a wide range of materials for structural containment Nb-1Zr has been selected for use as the structural container for the LANL ABC/ATW molten lead target. Corrosion and mass transfer behavior for various candidate structural materials in liquid lead are reviewed, together with the beneficial effects of inhibitors and various coatings to protect substrate against liquid lead corrosion. Mechanical properties of some candidate materials at elevated temperatures and the property changes resulting from 800 MeV proton irradiation are also reviewed

  20. Scientific objectives and selection of targets for the SMART-1 Infrared Spectrometer (SIR)

    Science.gov (United States)

    Basilevsky, A.T.; Keller, H.U.; Nathues, A.; Mall, U.; Hiesinger, H.; Rosiek, M.

    2004-01-01

    The European SMART-1 mission to the Moon, primarily a testbed for innovative technologies, was launched in September 2003 and will reach the Moon in 2005. On board are several scientific instruments, including the point-spectrometer SMART-1 Infrared Spectrometer (SIR). Taking into account the capabilities of the SMART-1 mission and the SIR instrument in particular, as well as the open questions in lunar science, a selection of targets for SIR observations has been compiled. SIR can address at least five topics: (1) Surface/regolith processes; (2) Lunar volcanism; (3) Lunar crust structure; (4) Search for spectral signatures of ices at the lunar poles; and (5) Ground truth and study of geometric effects on the spectral shape. For each topic we will discuss specific observation modes, necessary to achieve our scientific goals. The majority of SIR targets will be observed in the nadir-tracking mode. More than 100 targets, which require off-nadir pointing and off-nadir tracking, are planned. It is expected that results of SIR observations will significantly increase our understanding of the Moon. Since the exact arrival date and the orbital parameters of the SMART-1 spacecraft are not known yet, a more detailed planning of the scientific observations will follow in the near future. ?? 2004 Elsevier Ltd. All rights reserved.

  1. Akt mediated ROS-dependent selective targeting of mutant KRAS tumors.

    Science.gov (United States)

    Iskandar, Kartini; Rezlan, Majidah; Pervaiz, Shazib

    2014-10-01

    Reactive oxygen species (ROS) play a critical role in a variety of cellular processes, ranging from cell survival and proliferation to cell death. Previously, we reported the ability of a small molecule compound, C1, to induce ROS dependent autophagy associated apoptosis in human cancer cell lines and primary tumor cells (Wong C. et al. 2010). Our ongoing investigations have unraveled a hitherto undefined novel signaling network involving hyper-phosphorylation of Akt and Akt-mediated ROS production in cancer cell lines. Interestingly, drug-induced Akt activation is selectively seen in cell lines that carry mutant KRAS; HCT116 cells that carry the V13D KRAS mutation respond favorably to C1 while HT29 cells expressing wild type KRAS are relatively resistant. Of note, not only does the compound target mutant KRAS expressing cells but also induces RAS activation as evidenced by the PAK pull down assay. Corroborating this, pharmacological inhibition as well as siRNA mediated silencing of KRAS or Akt, blocked C1-induced ROS production and rescued tumor colony forming ability in HCT116 cells. To further confirm the involvement of KRAS, we made use of mutant KRAS transformed RWPE-1 prostate epithelial cells. Notably, drug-induced ROS generation and death sensitivity was significantly higher in RWPE-1-KRAS cells than the RWPE-1-vector cells, thus confirming the results obtained with mutant KRAS colorectal carcinoma cell line. Lastly, we made use of HCT116 mutant KRAS knockout cells (KO) where the mutant KRAS allele had been deleted, thus expressing a single wild-type KRAS allele. Exposure of the KO cells to C1 failed to induce Akt activation and mitochondrial ROS production. Taken together, results show the involvement of activated Akt in ROS-mediated selective targeting of mutant KRAS expressing tumors, which could have therapeutic implications given the paucity of chemotherapeutic strategies specifically targeting KRAS mutant cancers. PMID:26461287

  2. Selective target inactivation rather than global metabolic dormancy causes antibiotic tolerance in uropathogens.

    Science.gov (United States)

    Goneau, Lee W; Yeoh, Nigel S; MacDonald, Kyle W; Cadieux, Peter A; Burton, Jeremy P; Razvi, Hassan; Reid, Gregor

    2014-01-01

    Persister cells represent a multidrug-tolerant (MDT), physiologically distinct subpopulation of bacteria. The ability of these organisms to survive lethal antibiotic doses raises concern over their potential role in chronic disease, such as recurrent urinary tract infection (RUTI). Persistence is believed to be conveyed through global metabolic dormancy, which yields organisms unresponsive to external stimuli. However, recent studies have contested this stance. Here, various antibiotics that target different cellular processes were used to dissect the activity of transcription, translation, and peptidoglycan turnover in persister cells. Differential susceptibility patterns were found in type I and type II persisters, and responses differed between Staphylococcus saprophyticus and Escherichia coli uropathogens. Further, SOS-deficient strains were sensitized to ciprofloxacin, suggesting DNA gyrase activity in persisters and indicating the importance of active DNA repair systems for ciprofloxacin tolerance. These results indicate that global dormancy per se cannot sufficiently account for antibiotic tolerance. Rather, the activity of individual cellular processes dictates multidrug tolerance in an antibiotic-specific fashion. Furthermore, the susceptibility patterns of persisters depended on their mechanisms of onset, with subinhibitory antibiotic pretreatments selectively shutting down cognate targets and increasing the persister fraction against the same agent. Interestingly, antibiotics targeting transcription and translation enhanced persistence against multiple agents indirectly related to these processes. Conducting these assays with uropathogenic E. coli isolated from RUTI patients revealed an enriched persister fraction compared to organisms cleared with standard antibiotic therapy. This finding suggests that persister traits are either selected for during prolonged antibiotic treatment or initially contribute to therapy failure. PMID:24449771

  3. Target Selection Signals Influence Perceptual Decisions by Modulating the Onset and Rate of Evidence Accumulation.

    Science.gov (United States)

    Loughnane, Gerard M; Newman, Daniel P; Bellgrove, Mark A; Lalor, Edmund C; Kelly, Simon P; O'Connell, Redmond G

    2016-02-22

    Computational and neurophysiological research has highlighted neural processes that accumulate sensory evidence for perceptual decisions [1]. These processes have been studied in the context of highly simplified perceptual discrimination paradigms in which the physical evidence appears at times and locations that are either entirely predictable or exogenously cued (e.g., by the onset of the stimulus itself). Yet, we are rarely afforded such certainty in everyday life. For example, when driving along a busy motorway, we must continually monitor the movements of surrounding vehicles for events that call for a lane change. In such scenarios, it is unknown which of the continuously present information sources will become relevant or when. Although it is well established that evidence integration provides an effective mechanism for countering the impact of noise [2], the question of how this mechanism is implemented in the face of uncertain evidence onsets has yet to be answered. Here, we show that when monitoring two potential sources of information for evidence occurring unpredictably in both time and space, the human brain employs discrete, early target selection signals that significantly modulate the onset and rate of neural evidence accumulation, and thereby the timing and accuracy of perceptual reports. These selection signals share many of the key characteristics of the N2pc component highlighted in the literature on visual search [3, 4] yet are present even in the absence of distractors and under situations of low temporal and spatial uncertainty. These data provide novel insights into how target selection supports decision making in uncertain environments. PMID:26853360

  4. Bezielle selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS.

    Directory of Open Access Journals (Sweden)

    Vivian Chen

    Full Text Available Bezielle (BZL101 is a candidate oral drug that has shown promising efficacy and excellent safety in the early phase clinical trials for advanced breast cancer. Bezielle is an aqueous extract from the herb Scutellaria barbata. We have reported previously that Bezielle was selectively cytotoxic to cancer cells while sparing non-transformed cells. In tumor, but not in non-transformed cells, Bezielle induced generation of ROS and severe DNA damage followed by hyperactivation of PARP, depletion of the cellular ATP and NAD, and inhibition of glycolysis. We show here that tumor cells' mitochondria are the primary source of reactive oxygen species induced by Bezielle. Treatment with Bezielle induces progressively higher levels of mitochondrial superoxide as well as peroxide-type ROS. Inhibition of mitochondrial respiration prevents generation of both types of ROS and protects cells from Bezielle-induced death. In addition to glycolysis, Bezielle inhibits oxidative phosphorylation in tumor cells and depletes mitochondrial reserve capacity depriving cells of the ability to produce ATP. Tumor cells lacking functional mitochondria maintain glycolytic activity in presence of Bezielle thus supporting the hypothesis that mitochondria are the primary target of Bezielle. The metabolic effects of Bezielle towards normal cells are not significant, in agreement with the low levels of oxidative damage that Bezielle inflicts on them. Bezielle is therefore a drug that selectively targets cancer cell mitochondria, and is distinguished from other such drugs by its ability to induce not only inhibition of OXPHOS but also of glycolysis. This study provides a better understanding of the mechanism of Bezielle's cytotoxicity, and the basis of its selectivity towards cancer cells.

  5. Selective Vitamin D Receptor Activation as Anti-Inflammatory Target in Chronic Kidney Disease

    Directory of Open Access Journals (Sweden)

    J. Donate-Correa

    2014-01-01

    Full Text Available Paricalcitol, a selective vitamin D receptor (VDR activator used for treatment of secondary hyperparathyroidism in chronic kidney disease (CKD, has been associated with survival advantages, suggesting that this drug, beyond its ability to suppress parathyroid hormone, may have additional beneficial actions. In this prospective, nonrandomised, open-label, proof-of-concept study, we evaluated the hypothesis that selective vitamin D receptor activation with paricalcitol is an effective target to modulate inflammation in CKD patients. Eight patients with an estimated glomerular filtration rate between 15 and 44 mL/min/1.73 m2 and an intact parathyroid hormone (PTH level higher than 110 pg/mL received oral paricalcitol (1 μg/48 hours as therapy for secondary hyperparathyroidism. Nine patients matched by age, sex, and stage of CKD, but a PTH level <110 pg/mL, were enrolled as a control group. Our results show that five months of paricalcitol administration were associated with a reduction in serum concentrations of hs-CRP (13.9%, P<0.01, TNF-α (11.9%, P=0.01, and IL-6 (7%, P<0.05, with a nonsignificant increase of IL-10 by 16%. In addition, mRNA expression levels of the TNFα and IL-6 genes in peripheral blood mononuclear cells decreased significantly by 30.8% (P=0.01 and 35.4% (P=0.01, respectively. In conclusion, selective VDR activation is an effective target to modulate inflammation in CKD.

  6. Application of CellDesigner to the Selection of Anticancer Drug Targets: Test Case using P53

    OpenAIRE

    Isea, Raul; Hoebeke, Johan; Mayo, Rafael; Alvarez, Fernando; Holmes, David S.

    2013-01-01

    Cancer is a disease involving many genes, consequently it has been difficult to design anticancer drugs that are efficacious over a broad range of cancers. The robustness of cellular responses to gene knockout and the need to reduce undesirable side effects also contribute to the problem of effective anti-cancer drug design. To promote the successful selection of drug targets, each potential target should be subjected to a systems biology scrutiny to locate effective and specific targets whil...

  7. A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors

    Energy Technology Data Exchange (ETDEWEB)

    Kumar, Rajeev; Verma, Vikas; Sharma, Vikas; Jain, Ashish; Singh, Vishal [Division of Endocrinology, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Sarswat, Amit [Division of Medicinal & Process Chemistry, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Maikhuri, Jagdamba P. [Division of Endocrinology, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Sharma, Vishnu L. [Division of Medicinal & Process Chemistry, CSIR—Central Drug Research Institute, Lucknow 226 031 (India); Gupta, Gopal, E-mail: g_gupta@cdri.res.in [Division of Endocrinology, CSIR—Central Drug Research Institute, Lucknow 226 031 (India)

    2015-03-15

    Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~ 25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P < 0.01) and increased expression of ER-β target TNF-α (P < 0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization. - Highlights: • BP with benzopyran core of genistein was identified for ER-β selective action. • BP was 14-times more potent than genistien in targeting prostate cancer cells. • It behaved as a potent ER-β agonist and ER-α antagonist in gene reporter assays. • BP's anti-proliferative action was inhibited significantly in ER-β deficient cells. • BP — a unique lead

  8. A precisely substituted benzopyran targets androgen refractory prostate cancer cells through selective modulation of estrogen receptors

    International Nuclear Information System (INIS)

    Dietary consumption of phytoestrogens like genistein has been linked with lower incidence of prostate cancer. The estradiol-like benzopyran core of genistein confers estrogen receptor-β (ER-β) selectivity that imparts weak anti-proliferative activity against prostate cancer cells. DL-2-[4-(2-piperidinoethoxy)phenyl]-3-phenyl-2H-1-benzopyran (BP), a SERM designed with benzopyran core, targeted androgen independent prostate cancer (PC-3) cells 14-times more potently than genistein, ~ 25% more efficiently than tamoxifen and 6.5-times more actively than ICI-182780, without forfeiting significant specificity in comparison to genistein. BP increased apoptosis (annexin-V and TUNEL labeling), arrested cell cycle, and significantly increased caspase-3 activity along with mRNA expressions of estrogen receptor (ER)-β and FasL (qPCR) in PC-3 cells. In classical ERE-luc reporter assay BP behaved as a potent ER-α antagonist and ER-β agonist. Accordingly, it decreased expression of ER-α target PS2 (P < 0.01) and increased expression of ER-β target TNF-α (P < 0.05) genes in PC-3. ER-β deficient PC-3 (siRNA-transfected) was resistant to apoptotic and anti-proliferative actions of SERMs, including stimulation of FasL expression by BP. BP significantly inhibited phosphorylation of Akt and ERK-1/2, JNK and p38 in PC-3 (immunoblotting), and thus adopted a multi-pathway mechanism to exert a more potent anti-proliferative activity against prostate cancer cells than natural and synthetic SERMs. Its precise ER-subtype specific activity presents a unique lead structure for further optimization. - Highlights: • BP with benzopyran core of genistein was identified for ER-β selective action. • BP was 14-times more potent than genistien in targeting prostate cancer cells. • It behaved as a potent ER-β agonist and ER-α antagonist in gene reporter assays. • BP's anti-proliferative action was inhibited significantly in ER-β deficient cells. • BP — a unique lead

  9. Selection between Michaelis-Menten and target-mediated drug disposition pharmacokinetic models.

    Science.gov (United States)

    Yan, Xiaoyu; Mager, Donald E; Krzyzanski, Wojciech

    2010-02-01

    Target-mediated drug disposition (TMDD) models have been applied to describe the pharmacokinetics of drugs whose distribution and/or clearance are affected by its target due to high binding affinity and limited capacity. The Michaelis-Menten (M-M) model has also been frequently used to describe the pharmacokinetics of such drugs. The purpose of this study is to investigate conditions for equivalence between M-M and TMDD pharmacokinetic models and provide guidelines for selection between these two approaches. Theoretical derivations were used to determine conditions under which M-M and TMDD pharmacokinetic models are equivalent. Computer simulations and model fitting were conducted to demonstrate these conditions. Typical M-M and TMDD profiles were simulated based on literature data for an anti-CD4 monoclonal antibody (TRX1) and phenytoin administered intravenously. Both models were fitted to data and goodness of fit criteria were evaluated for model selection. A case study of recombinant human erythropoietin was conducted to qualify results. A rapid binding TMDD model is equivalent to the M-M model if total target density R ( tot ) is constant, and R ( tot ) K ( D ) /(K ( D ) + C) ( 2 ) < 1 where K ( D ) represents the dissociation constant and C is the free drug concentration. Under these conditions, M-M parameters are defined as: V ( max ) = k ( int ) R ( tot ) V ( c ) and K ( m ) = K ( D ) where k ( int ) represents an internalization rate constant, and V ( c ) is the volume of the central compartment. R ( tot ) is constant if and only if k ( int ) = k ( deg,) where k ( deg ) is a degradation rate constant. If the TMDD model predictions are not sensitive to k ( int ) or k ( deg ) parameters, the condition of R ( tot ) K ( D ) /(K ( D ) + C) ( 2 ) < 1 alone can preserve the equivalence between rapid binding TMDD and M-M models. The model selection process for drugs that exhibit TMDD should involve a full mechanistic model as well as reduced models. The best model

  10. Selective TDDFT with automatic removal of ghost transitions: application to a perylene-dye-sensitized solar cell model

    OpenAIRE

    Kovyrshin, Arseny; De Angelis, Filippo; Neugebauer, Johannes

    2012-01-01

    We present an application of a selective time-dependent density-functional theory (TDDFT) scheme to a model for a dye-sensitized solar cell (DSSC) with a perylene sensitizer dye on a TiO2 nanoparticle model. In an earlier study on this system [De Angelis, Chem. Phys. Lett., 2010, 493, 323], it was reported that a large number of conduction-band excitations severely complicate the identification of the bright p - p* excitations of the perylene dye. Here, we show that this proble...

  11. Automatic selection of optimal cardiac-phase in coronary CT angiography. Its clinical usefulness for patients with atrial fibrillation

    International Nuclear Information System (INIS)

    The optimal cardiac phases for coronary CT angiography (CTA) are end-systole and mid-diastole, in which cardiac movement is slow. In conventional methods, these cardiac phases are determined by visual selection. We have compared the images in the optimal cardiac phases that were selected by the conventional method and cardiac-phase search software (Phase Navi), and examined the clinical usefulness of Phase Navi in patients with atrial fibrillation. The subjects were 38 patients (regular rhythm: 20, atrial fibrillation: 18). The continuity scores of patients with regular rhythm (Phase Navi, conventional methods) were 2.4±0.3-2.5±0.3 in end-systole and 2.4±0.5-2.4±0.4 in mid-diastole. The scores of patients with atrial fibrillation (Phase Navi, conventional methods) were 2.3±0.4-2.3±0.4 in end-systole, and 2.2±0.5-2.1±0.6 in mid-diastole. Because the continuity scores of the optimal images from Phase Navi were similar to those from the conventional method, Phase Navi had clinical usefulness in patients with atrial fibrillation. (author)

  12. Pharmacological targeting of dopamine D3 receptors: Possible clinical applications of selective drugs.

    Science.gov (United States)

    Pich, Emilio Merlo; Collo, Ginetta

    2015-09-01

    Dopamine D3 receptors have been pharmacologically engaged in humans since the development of the first antipsychotics and ergot-derivative dopamine (DA) agonists, even without knowing it. These agents were generally non-selective, developed primarily to target D2 receptors. In the last 10 years the understanding of the clinical implication of D3 receptors has been progressing also due to the identification of D3 gene polymorphisms, the use of more selective PET ligands such as [(11)C]-(+)-PHNO and the learning regarding the clinical use of the D3-preferential D2/D3 agonists ropinirole and pramipexole. A new specific neuroplasticity role of D3 receptor regarding dendrite arborisation outgrowth in dopaminergic neurons was also proposed to support, at least in part, the slowing of disease observed in subjects with Parkinson׳s Disease treated with DA agonists. Similar mechanisms could be at the basis of the antidepressant-like effects observed with DA agonists when co-administered with standard of care. Severe adverse event occurring with the use of anti-parkinsonian DA agonists in predisposed subjects, i.e., impulse control disorders, are now suggested to be putatively related to overactive D3 receptors. Not surprisingly, blockade of D3 receptors was proposed as treatment for addictive disorders, a goal that could be potentially achieved by repositioning buspirone, an anxiolytic drug with D3-preferential antagonistic features, or with novel selective D3 antagonists or partial agonists currently in development for schizophrenia. At the moment ABT-925 is the only selective D3 antagonist tested in schizophrenic patients in Phase II, showing an intriguing cognitive enhancing effects supported by preclinical data. Finally, exploratory pharmacogenetic analysis suggested that ABT-925 could be effective in a subpopulation of patients with a polymorphism on the D3 receptor, opening to a possible personalised medicine approach. PMID:26298833

  13. Discussion of Automatic Control Valve Model Selection for Coal Gasification Working Condition%煤气化工况自控阀门选型探讨

    Institute of Scientific and Technical Information of China (English)

    刘志伟

    2013-01-01

    Automatic control valve plays a crucial role for the stable running of coal gasification plant. The water slurry gasification process is briefly described. The harsh conditions for coal slurry valve, oxygen valve, synthesis gas venting valve, lock slag valve, black water valve are evaluated according to the process characteristic. Based on the successful operating experience of same process, the valve design selection is discussed primarily. The advice on valve type, material, internals, sealed level and special treatment are given. It provides reference for instrument selection of similar process apparatus.%煤气化装置运行稳定与否,自控阀门起着关键的作用.简要介绍了水煤浆气化工艺,根据其工艺特征分别分析了煤浆阀、氧气阀、合成气放空阀、锁渣阀、黑水阀的严酷工况.依据同行业成功运行经验,重点对以上阀门的设计选型进行探讨,对阀门形式、材质、内件、密封等级及特殊处理给出了建议,为同类工艺装置的仪表选型提供了参考依据.

  14. Attenuation-based automatic kilovoltage selection and sonogram-affirmed iterative reconstruction: Effects on radiation exposure and image quality of portal-phase liver CT

    International Nuclear Information System (INIS)

    To compare the radiation dose and image quality between standard-dose CT and a low-dose CT obtained with the combined use of an attenuation-based automatic kilovoltage (kV) selection tool (CARE kV) and sonogram-affirmed iterative reconstruction (SAFIRE) for contrast-enhanced CT examination of the liver. We retrospectively reviewed 67 patients with chronic liver disease in whom both, standard-dose CT with 64-slice multidetector-row CT (MDCT) (protocol A), and low-dose CT with 128-slice MDCT using CARE kV and SAFIRE (protocol B) were performed. Images from protocol B during the portal phase were reconstructed using either filtered back projection or SAFIRE with 5 different iterative reconstruction (IR) strengths. We performed qualitative and quantitative analyses to select the appropriate IR strength. Reconstructed images were then qualitatively and quantitatively compared with protocol A images. Qualitative and quantitative analysis of protocol B demonstrated that SAFIRE level 2 (S2) was most appropriate in our study. Qualitative and quantitative analysis comparing S2 images from protocol B with images from protocol A, showed overall good diagnostic confidence of S2 images despite a significant radiation dose reduction (47% dose reduction, p < 0.001). Combined use of CARE kV and SAFIRE allowed significant reduction in radiation exposure while maintaining image quality in contrast-enhanced liver CT.

  15. Plausible improvements for selective targeting of dopamine receptors in therapy of Parkinson's disease.

    Science.gov (United States)

    Luthra, Pratibha Mehta; Kumar, J B Senthil

    2012-12-01

    Parkinson's disease (PD) is a neurodegenerative condition characterized by progressive and profound loss of dopaminergic neurons in the substantia nigra pars compacta leading to the formation of eosinophillic, intracytoplamic, proteinacious inclusions termed as lewy bodies. L-dopa remains as a gold standard for the treatment of PD, and is often combined with carbidopa to reduce the dose-limiting side effects. Long-term levodopa treatment is associated with the development of motor fluctuations and peak dose dyskinesias. Dopamine Replacement Therapy (DRT) with dopamine agonists (DAs) (ropinirole and pramipexole) is used to manage complications of L-dopa treatment, however, has been associated with numerous pharmacovigilence reports. The present review attempts to narrate the multiple receptor interaction of DAs followed by the assessment of their side effects during the treatment of PD and possible remedial strategy for selective targeting of dopamine receptors to overcome these affects in therapy of Parkinson's disease. PMID:22697513

  16. Targeted Multiplexed Selected Reaction Monitoring Analysis Evaluates Protein Expression Changes of Molecular Risk Factors for Major Psychiatric Disorders

    OpenAIRE

    Wesseling, Hendrik; Gottschalk, Michael G.; Bahn, Sabine

    2014-01-01

    Background: Extensive research efforts have generated genomic, transcriptomic, proteomic, and functional data hoping to elucidate psychiatric pathophysiology. Selected reaction monitoring, a recently developed targeted proteomic mass spectrometric approach, has made it possible to evaluate previous findings and hypotheses with high sensitivity, reproducibility, and quantitative accuracy. Methods: Here, we have developed a labelled multiplexed selected reaction monitoring assay, comprising 56 ...

  17. Visual encoding and fixation target selection in free viewing: presaccadic brain potentials

    Directory of Open Access Journals (Sweden)

    Andrey R Nikolaev

    2013-06-01

    Full Text Available In scrutinizing a scene, the eyes alternate between fixations and saccades. During a fixation, two component processes can be distinguished: visual encoding and selection of the next fixation target. We aimed to distinguish the neural correlates of these processes in the electrical brain activity prior to a saccade onset. Participants viewed color photographs of natural scenes, in preparation for a change detection task. Then, for each participant and each scene we computed an image heat map, with temperature representing the duration and density of fixations. The temperature difference between the start and end points of saccades was taken as a measure of the expected task-relevance of the information concentrated in specific regions of a scene. Visual encoding was evaluated according to whether subsequent change was correctly detected. Saccades with larger temperature difference were more likely to be followed by correct detection than ones with smaller temperature differences. The amplitude of presaccadic activity over anterior brain areas was larger for correct detection than for detection failure. This difference was observed for short “scrutinizing” but not for long “explorative” saccades, suggesting that presaccadic activity reflects top-down saccade guidance. Thus, successful encoding requires local scanning of scene regions which are expected to be task-relevant. Next, we evaluated fixation target selection. Saccades “moving up” in temperature were preceded by presaccadic activity of higher amplitude than those “moving down”. This finding suggests that presaccadic activity reflects attention deployed to the following fixation location. Our findings illustrate how presaccadic activity can elucidate concurrent brain processes related to the immediate goal of planning the next saccade and the larger-scale goal of constructing a robust representation of the visual scene.

  18. Targeted metabolomics of Gammarus pulex following controlled exposures to selected pharmaceuticals in water.

    Science.gov (United States)

    Gómez-Canela, Cristian; Miller, Thomas H; Bury, Nicolas R; Tauler, Romà; Barron, Leon P

    2016-08-15

    The effects of pharmaceuticals and personal care products (PPCPs) on aquatic organisms represent a significant current concern. Herein, a targeted metabolomics approach using liquid chromatography-high resolution mass spectrometry (LC-HRMS) is presented to characterise concentration changes in 29 selected metabolites following exposures of aquatic invertebrates, Gammarus pulex, to pharmaceuticals. Method performance revealed excellent linearity (R(2)>0.99), precision (0.1-19%) and lower instrumental limits of detection (0.002-0.20ng) for all metabolites studied. Three pharmaceuticals were selected representing the low, middle and high range of measured acute measured toxicities (of a total of 26 compounds). Gammarids were exposed to both the no-observed-adverse-effect-level (NOAEL) and the lowest-observed-adverse-effect-level (LOAEL) of triclosan (0.1 and 0.3mgL(-1)), nimesulide (0.5 and 1.4mgL(-1)) and propranolol (100 and 153mgL(-1)) over 24h. Quantitative metabolite profiling was then performed. Significant changes in metabolite concentrations relative to controls are presented and display distinct clustered trends for each pharmaceutical. Approximately 37% (triclosan), 33% (nimesulide) and 46% (propranolol) of metabolites showed statistically significant time-related effects. Observed changes are also discussed with respect to internal concentrations of the three pharmaceuticals measured using a method based on pulverised liquid extraction, solid phase extraction and LC-MS/MS. Potential metabolic pathways that may be affected by such exposures are also discussed. This represents the first study focussing on quantitative, targeted metabolomics of this lower trophic level benthic invertebrate that may elucidate biomarkers for future risk assessment. PMID:27110989

  19. Local node selection for target tracking based on underwater wireless sensor networks

    Science.gov (United States)

    Zhang, Qiang; Zhang, Chaojie; Liu, Meiqin; Zhang, Senlin

    2015-12-01

    Traditional sonar-array-based target tracking algorithms may be unsuitable for on-demand tracking missions, since they assume that the sonar arrays should be towed or mounted by a submarine or a ship. Alternatively, underwater wireless sensor networks can offer a promising solution approach. First, each underwater node is battery-powered, so saving energy expenditure is a critical issue. Instead of keeping all sensor nodes active, this paper provides a local node selection (LNS) scheme which increases energy efficiency by waking up only a small part of nodes at each time. Second, considering node's limited computing ability and the real-time requirement for the tracking algorithm, instead of employing the centralised fusion structure, we utilise the distributed Kalman filtering fusion with feedback in this paper. Finally, instead of assuming one sensor node can uniquely determine target's location, a more practical range-only measurement model is proposed. Then the LNS scheme and distributed fusion with feedback are extended to our range-only measurement model. The simulation results demonstrate the efficiency of our scheme.

  20. Asteroid Target Selection and Orbital Manipulation Sensitivity for Deflection Demonstration Missions

    Science.gov (United States)

    Sanchez, J. P.

    2015-06-01

    In recent years, space agencies have begun to seriously consider launching demonstration missions to test some of the asteroid orbital deflection technologies and methods that have been studied and discussed in the scientific literature. Consequently, several mission studies have already been carried out. This paper attempts to gain new insights into the target selection process by analyzing the orbital evolution of a large set of notional accessible asteroids that cover all types of Near Earth Object families. The evolution of their unperturbed orbits and their anthropogenically modified trajectories was compared, and a measure of the resilience of a given orbit to anthropogenic manipulation was taken (i.e., orbital innocuity). The results show that pruning criteria such as considering only Amor objects (i.e., non-Earth-crossers) reduce unnecessarily the population of potential suitable targets and that within large regions of Earth-crossing orbital space asteroids can be found that are both accessible and safe to manipulate from the standpoint of the Earth impact risk.

  1. FAMACHA©: A potential tool for targeted selective treatment of chronic fasciolosis in sheep.

    Science.gov (United States)

    Olah, Sophie; van Wyk, Jan A; Wall, Richard; Morgan, Eric R

    2015-09-15

    The liver fluke Fasciola hepatica causes considerable damage to the health, welfare and productivity of ruminants in temperate areas, and its control is challenged by anthelmintic resistance. Targeted selective treatment (TST) is an increasingly established strategy for preserving anthelmintic efficacy in grazing livestock, yet no practical indicators are available to target individuals for treatment against fluke infection. This paper evaluates the FAMACHA(©) system, a colour chart for the non-invasive detection of anaemia in small ruminants, for this purpose. FAMACHA(©) scores were collected from 288 sheep prior to slaughter during the winter period, when fluke infections were largely mature, and condemned livers were recovered and adult flukes extracted. Average FAMACHA(©) score was significantly higher (=paler conjunctivae) in animals whose livers were condemned (3.6, n=62) than in those whose livers were not condemned (2.1). The number of adult flukes recovered ranged from 2 to 485, and was positively correlated with FAMACHA(©) score (r(2)=0.54, phepatica, in support of refugia-based control of fluke and nematode infections, and further field evaluation is warranted. PMID:26223154

  2. A structural annotation resource for the selection of putative target proteins in the malaria parasite

    Directory of Open Access Journals (Sweden)

    Joubert Fourie

    2008-05-01

    Full Text Available Abstract Background Protein structure plays a pivotal role in elucidating mechanisms of parasite functioning and drug resistance. Moreover, protein structure aids the determination of protein function, which can together with the structure be used to identify novel drug targets in the parasite. However, various structural features in Plasmodium falciparum proteins complicate the experimental determination of protein structures. Limited similarity to proteins in the Protein Data Bank and the shortage of solved protein structures in the malaria parasite necessitate genome-scale structural annotation of P. falciparum proteins. Additionally, the annotation of a range of structural features facilitates the identification of suitable targets for experimental and computational studies. Methods An integrated structural annotation system was developed and applied to P. falciparum, Plasmodium vivax and Plasmodium yoelii. The annotation included searches for sequence similarity, patterns and domains in addition to the following predictions: secondary structure, transmembrane helices, protein disorder, low complexity, coiled-coils and small molecule interactions. Subsequently, candidate proteins for further structural studies were identified based on the annotated structural features. Results The annotation results are accessible through a web interface, enabling users to select groups of proteins which fulfil multiple criteria pertaining to structural and functional features 1. Analysis of features in the P. falciparum proteome showed that protein-interacting proteins contained a higher percentage of predicted disordered residues than non-interacting proteins. Proteins interacting with 10 or more proteins have a disordered content concentrated in the range of 60–100%, while the disorder distribution for proteins having only one interacting partner, was more evenly spread. Conclusion A series of P. falciparum protein targets for experimental structure

  3. Dipeptidyl peptidase IV as a potential target for selective prodrug activation and chemotherapeutic action in cancers.

    Science.gov (United States)

    Dahan, Arik; Wolk, Omri; Yang, Peihua; Mittal, Sachin; Wu, Zhiqian; Landowski, Christopher P; Amidon, Gordon L

    2014-12-01

    The efficacy of chemotherapeutic drugs is often offset by severe side effects attributable to poor selectivity and toxicity to normal cells. Recently, the enzyme dipeptidyl peptidase IV (DPPIV) was considered as a potential target for the delivery of chemotherapeutic drugs. The purpose of this study was to investigate the feasibility of targeting chemotherapeutic drugs to DPPIV as a strategy to enhance their specificity. The expression profile of DPPIV was obtained for seven cancer cell lines using DNA microarray data from the DTP database, and was validated by RT-PCR. A prodrug was then synthesized by linking the cytotoxic drug melphalan to a proline-glycine dipeptide moiety, followed by hydrolysis studies in the seven cell lines with a standard substrate, as well as the glycyl-prolyl-melphalan (GP-Mel). Lastly, cell proliferation studies were carried out to demonstrate enzyme-dependent activation of the candidate prodrug. The relative RT-PCR expression levels of DPPIV in the cancer cell lines exhibited linear correlation with U95Av2 Affymetrix data (r(2) = 0.94), and with specific activity of a standard substrate, glycine-proline-p-nitroanilide (r(2) = 0.96). The significantly higher antiproliferative activity of GP-Mel in Caco-2 cells (GI₅₀ = 261 μM) compared to that in SK-MEL-5 cells (GI₅₀ = 807 μM) was consistent with the 9-fold higher specific activity of the prodrug in Caco-2 cells (5.14 pmol/min/μg protein) compared to SK-MEL-5 cells (0.68 pmol/min/μg protein) and with DPPIV expression levels in these cells. Our results demonstrate the great potential to exploit DPPIV as a prodrug activating enzyme for efficient chemotherapeutic drug targeting. PMID:25365774

  4. Identification of cytotoxic drugs that selectively target tumor cells with MYC overexpression.

    Directory of Open Access Journals (Sweden)

    Anna Frenzel

    Full Text Available Expression of MYC is deregulated in a wide range of human cancers, and is often associated with aggressive disease and poorly differentiated tumor cells. Identification of compounds with selectivity for cells overexpressing MYC would hence be beneficial for the treatment of these tumors. For this purpose we used cell lines with conditional MYCN or c-MYC expression, to screen a library of 80 conventional cytotoxic compounds for their ability to reduce tumor cell viability and/or growth in a MYC dependent way. We found that 25% of the studied compounds induced apoptosis and/or inhibited proliferation in a MYC-specific manner. The activities of the majority of these were enhanced both by c-MYC or MYCN over-expression. Interestingly, these compounds were acting on distinct cellular targets, including microtubules (paclitaxel, podophyllotoxin, vinblastine and topoisomerases (10-hydroxycamptothecin, camptothecin, daunorubicin, doxorubicin, etoposide as well as DNA, RNA and protein synthesis and turnover (anisomycin, aphidicholin, gliotoxin, MG132, methotrexate, mitomycin C. Our data indicate that MYC overexpression sensitizes cells to disruption of specific pathways and that in most cases c-MYC and MYCN overexpression have similar effects on the responses to cytotoxic compounds. Treatment of the cells with topoisomerase I inhibitors led to down-regulation of MYC protein levels, while doxorubicin and the small molecule MYRA-A was found to disrupt MYC-Max interaction. We conclude that the MYC pathway is only targeted by a subset of conventional cytotoxic drugs currently used in the clinic. Elucidating the mechanisms underlying their specificity towards MYC may be of importance for optimizing treatment of tumors with MYC deregulation. Our data also underscores that MYC is an attractive target for novel therapies and that cellular screenings of chemical libraries can be a powerful tool for identifying compounds with a desired biological activity.

  5. Method for Automatic Tube Current Selection for Obtaining a Consistent Image Quality and Dose Optimization in a Cardiac Multidetector CT

    International Nuclear Information System (INIS)

    To evaluate a quantitative method for individually adjusting the tube current to obtain images with consistent noise in electrocardiogram (ECG)-gated CT cardiac scans. The image noise from timing bolus and cardiac CT scans of 80 patients (Group A) who underwent a 64-row multidetector (MD) CT cardiac examination with patient-independent scan parameters were analyzed. A formula was established using the noise correlation between the timing bolus and cardiac scans. This formula was used to predict the required tube current to obtain the desired cardiac CT image noise based on the timing bolus noise measurement. Subsequently, 80 additional cardiac patients (Group B) were scanned with individually adjusted tube currents using an established formula to evaluate its ability to obtain accurate and consistent image noise across the patient population. Image quality was evaluated using score scale of 1 to 5 with a score of 3 or higher being clinically acceptable. Using the formula, we obtained an average CT image noise of 28.55 Hounsfield unit (HU), with a standard deviation of only 1.7 HU, as opposed to a target value of 28 HU. Image quality scores were 4.03 and 4.27 for images in Groups A and B, respectively, and there was no statistical difference between the image quality scores between the two groups. However, the average CT dose index (CTDIvol) was 30% lower for Group B. Adjusting the tube current based on timing bolus scans may provide a consistent image quality and dose optimization for cardiac patients of various body mass index values

  6. A Data Mining-Based Response Model for Target Selection in Direct Marketing

    Directory of Open Access Journals (Sweden)

    Eniafe Festus Ayetiran

    2012-02-01

    Full Text Available Identifying customers who are more likely to respond to new product offers is an important issue in direct marketing. In direct marketing, data mining has been used extensively to identify potential customers for a new product (target selection. Using historical purchase data, a predictive response model with data mining techniques was developed to predict a probability that a customer in Ebedi Microfinance bank will respond to a promotion or an offer. To achieve this purpose, a predictive response model using customers’ historical purchase data was built with data mining techniques. The data were stored in a data warehouse to serve as management decision support system. The response model was built from customers’ historic purchases and demographic dataset.Bayesian algorithm precisely Naïve Bayes algorithm was employed in constructing the classifier system. Both filter and wrapper feature selection techniques were employed in determining inputs to the model.The results obtained shows that Ebedi Microfinance bank can plan effective marketing of their products and services by obtaining a guiding report on the status of their customers which will go a long way in assisting management in saving significant amount of money that could have been spent on wasteful promotional campaigns.

  7. Optimal Decision Rules for Biomarker-Based Subgroup Selection for a Targeted Therapy in Oncology

    Directory of Open Access Journals (Sweden)

    Johannes Krisam

    2015-05-01

    Full Text Available Throughout recent years, there has been a rapidly increasing interest regarding the evaluation of so-called targeted therapies. These therapies are assumed to show a greater benefit in a pre-specified subgroup of patients—commonly identified by a predictive biomarker—as compared to the total patient population of interest. This situation has led to the necessity to develop biostatistical methods allowing an efficient evaluation of such treatments. Among others, adaptive enrichment designs have been proposed as a solution. These designs allow the selection of the most promising patient population based on an efficacy analysis at interim and restricting recruitment to these patients afterwards. As has recently been shown, the performance of the applied interim decision rule in such a design plays a crucial role in ensuring a successful trial. In this work, we investigate the situation when the primary outcome of the trial is a binary variable. Optimal decision rules are derived which incorporate the uncertainty about the treatment effects. These optimal decision rules are evaluated with respect to their performance in an adaptive enrichment design in terms of correct selection probability and power, and are compared to proposed ad hoc decision rules. Our methods are illustrated by means of a clinical trial example.

  8. Functionalizing Liposomes with anti-CD44 Aptamer for Selective Targeting of Cancer Cells.

    Science.gov (United States)

    Alshaer, Walhan; Hillaireau, Hervé; Vergnaud, Juliette; Ismail, Said; Fattal, Elias

    2015-07-15

    CD44 receptor protein is found to be overexpressed by many tumors and is identified as one of the most common cancer stem cell surface markers including tumors affecting colon, breast, pancreas, and head and neck, making this an attractive receptor for therapeutic targeting. In this study, 2'-F-pyrimidine-containing RNA aptamer (Apt1), previously selected against CD44, was successfully conjugated to the surface of PEGylated liposomes using the thiol-maleimide click reaction. The conjugation of Apt1 to the surface of liposomes was confirmed by the change in size and zeta potential and by migration on agarose gel electrophoresis. The binding affinity of Apt1 was improved after conjugation compared to free-Apt1. The cellular uptake for Apt1-Lip was tested by flow cytometry and confocal imaging using the two CD44(+) cell lines, human lung cancer cells (A549) and human breast cancer cells (MDA-MB-231), and the CD44(-) cell line, mouse embryonic fibroblast cells (NIH/3T3). The results showed higher sensitivity and selectivity for Apt1-Lip compared to the blank liposomes (Mal-Lip). In conclusion, we demonstrate a successful conjugation of anti-CD44 aptamer to the surface of liposome and binding preference of Apt1-Lip to CD44-expressing cancer cells and conclude to a promising potency of Apt1-Lip as a specific drug delivery system. PMID:25343502

  9. Identifying Human Genome-Wide CNV, LOH and UPD by Targeted Sequencing of Selected Regions.

    Directory of Open Access Journals (Sweden)

    Wei Li

    Full Text Available Copy-number variations (CNV, loss of heterozygosity (LOH, and uniparental disomy (UPD are large genomic aberrations leading to many common inherited diseases, cancers, and other complex diseases. An integrated tool to identify these aberrations is essential in understanding diseases and in designing clinical interventions. Previous discovery methods based on whole-genome sequencing (WGS require very high depth of coverage on the whole genome scale, and are cost-wise inefficient. Another approach, whole exome genome sequencing (WEGS, is limited to discovering variations within exons. Thus, we are lacking efficient methods to detect genomic aberrations on the whole genome scale using next-generation sequencing technology. Here we present a method to identify genome-wide CNV, LOH and UPD for the human genome via selectively sequencing a small portion of genome termed Selected Target Regions (SeTRs. In our experiments, the SeTRs are covered by 99.73%~99.95% with sufficient depth. Our developed bioinformatics pipeline calls genome-wide CNVs with high confidence, revealing 8 credible events of LOH and 3 UPD events larger than 5M from 15 individual samples. We demonstrate that genome-wide CNV, LOH and UPD can be detected using a cost-effective SeTRs sequencing approach, and that LOH and UPD can be identified using just a sample grouping technique, without using a matched sample or familial information.

  10. A Fixed-Target ExpeRiment at the LHC (AFTER@LHC) : luminosities, target polarisation and a selection of physics studies

    CERN Document Server

    Lansberg, J P; Didelez, J P; Genolini, B; Hadjidakis, C; Rosier, P; Arnaldi, R; Scomparin, E; Brodsky, S J; Ferreiro, E G; Fleuret, F; Rakotozafindrabe, A; Uggerhøj, U I

    2012-01-01

    We report on a future multi-purpose fixed-target experiment with the proton or lead ion LHC beams extracted by a bent crystal. The multi-TeV LHC beams allow for the most energetic fixed-target experiments ever performed. Such an experiment, tentatively named AFTER for "A Fixed-Target ExperRiment", gives access to new domains of particle and nuclear physics complementing that of collider experiments, in particular at RHIC and at the EIC projects. The instantaneous luminosity at AFTER using typical targets surpasses that of RHIC by more than 3 orders of magnitude. Beam extraction by a bent crystal offers an ideal way to obtain a clean and very collimated high-energy beam, without decreasing the performance of the LHC. The fixed-target mode also has the advantage of allowing for spin measurements with a polarised target and for an access over the full backward rapidity domain up to xF ~ - 1. Here, we elaborate on the reachable luminosities, the target polarisation and a selection of measurements with hydrogen an...

  11. Selective targeting of TGF-β activation to treat fibroinflammatory airway disease.

    Science.gov (United States)

    Minagawa, Shunsuke; Lou, Jianlong; Seed, Robert I; Cormier, Anthony; Wu, Shenping; Cheng, Yifan; Murray, Lynne; Tsui, Ping; Connor, Jane; Herbst, Ronald; Govaerts, Cedric; Barker, Tyren; Cambier, Stephanie; Yanagisawa, Haruhiko; Goodsell, Amanda; Hashimoto, Mitsuo; Brand, Oliver J; Cheng, Ran; Ma, Royce; McKnelly, Kate J; Wen, Weihua; Hill, Arthur; Jablons, David; Wolters, Paul; Kitamura, Hideya; Araya, Jun; Barczak, Andrea J; Erle, David J; Reichardt, Louis F; Marks, James D; Baron, Jody L; Nishimura, Stephen L

    2014-06-18

    Airway remodeling, caused by inflammation and fibrosis, is a major component of chronic obstructive pulmonary disease (COPD) and currently has no effective treatment. Transforming growth factor-β (TGF-β) has been widely implicated in the pathogenesis of airway remodeling in COPD. TGF-β is expressed in a latent form that requires activation. The integrin αvβ8 (encoded by the itgb8 gene) is a receptor for latent TGF-β and is essential for its activation. Expression of integrin αvβ8 is increased in airway fibroblasts in COPD and thus is an attractive therapeutic target for the treatment of airway remodeling in COPD. We demonstrate that an engineered optimized antibody to human αvβ8 (B5) inhibited TGF-β activation in transgenic mice expressing only human and not mouse ITGB8. The B5 engineered antibody blocked fibroinflammatory responses induced by tobacco smoke, cytokines, and allergens by inhibiting TGF-β activation. To clarify the mechanism of action of B5, we used hydrodynamic, mutational, and electron microscopic methods to demonstrate that αvβ8 predominantly adopts a constitutively active, extended-closed headpiece conformation. Epitope mapping and functional characterization of B5 revealed an allosteric mechanism of action due to locking-in of a low-affinity αvβ8 conformation. Collectively, these data demonstrate a new model for integrin function and present a strategy to selectively target the TGF-β pathway to treat fibroinflammatory airway diseases. PMID:24944194

  12. Uranium exploration target selection for proterozoic iron oxide/breccia complex type deposits in India

    International Nuclear Information System (INIS)

    Multimetal iron oxide/breccia complex (IOBC) type deposits exemplified by Olympic Dam in Australia, fall under low grade, large tonnage deposits. A multidisciplinary integrated exploration programme consisting of airborne surveys, ground geological surveys, geophysical and geochemical investigations and exploratory drilling, supported adequately by the state of the art analytical facilities, data processing using various software and digital image processing has shown moderate success in the identification of target areas for this type of deposits in the Proterozoic terrains of India. Intracratonic, anorogenic, continental rift to continental margin environment have been identified in a very wide spectrum of rock associations. The genesis and evolution of such associations during the Middle Proterozoic period have been reviewed and applied for target selection in the (i) Son-Narmada rift valley zone; (ii) areas covered by Dongargarh Supergroup of rocks in Madhya Pradesh; (iii) areas exposing ferruginous breccia in the western part of the Singhbhum Shear Zone (SSZ) around Lotapahar; (iv) Siang Group of rocks in Arunachal Pradesh; (v) Crystalline rocks of Garo Hills around Anek; and (vi) Chhotanagpur Gneissic complex in the Bahia-Ulatutoli tract of Ranchi Plateau. Of theses six areas, the Son-Narmada rift area appears to be the most promising area for IOBC type deposits. Considering occurrences of the uranium anomalies near Meraraich, Kundabhati, Naktu and Kudar and positive favourability criteria observed in a wide variety of rocks spatially related to the rifts and shears, certain sectors in Son-Narmada rift zone have been identified as promising for intense subsurface exploration. 20 refs, 4 figs, 1 tab

  13. Effects of automatic tube potential selection on radiation dose index, image quality, and lesion detectability in pediatric abdominopelvic CT and CTA: a phantom study

    Energy Technology Data Exchange (ETDEWEB)

    Brinkley, Michael F.; Choudhury, Kingshuk Roy; Frush, Donald P. [Duke University School of Medicine, Department of Radiology, DUMC Box 3808, Durham, NC (United States); Ramirez-Giraldo, Juan C. [Siemens Healthcare, Malvern (United States); Samei, Ehsan; Wilson, Joshua M.; Christianson, Olav I. [Duke University School of Medicine, Clinical Imaging Physics Group, Department of Radiology, Durham, NC (United States); Frush, Daniel J. [Duke University School of Medicine, Medical Physics, Durham, NC (United States)

    2016-01-15

    To assess the effect of automatic tube potential selection (ATPS) on radiation dose, image quality, and lesion detectability in paediatric abdominopelvic CT and CT angiography (CTA). A paediatric modular phantom with contrast inserts was examined with routine pitch (1.4) and high pitch (3.0) using a standard abdominopelvic protocol with fixed 120 kVp, and ATPS with variable kVp in non-contrast, contrast-enhanced, and CTA mode. The volume CT dose index (CTDI{sub vol}), contrast-to-noise ratio (CNR) and lesion detectability index (d') were compared between the standard protocol and ATPS examinations. CTDI{sub vol} was reduced in all routine pitch ATPS examinations, with dose reductions of 27-52 % in CTA mode (P < 0.0001), 15-33 % in contrast-enhanced mode (P = 0.0003) and 8-14 % in non-contrast mode (P = 0.03). Iodine and soft tissue insert CNR and d' were improved or maintained in all ATPS examinations. kVp and dose were reduced in 25 % of high pitch ATPS examinations and in none of the full phantom examinations obtained after a single full phantom localizer. ATPS reduces radiation dose while maintaining image quality and lesion detectability in routine pitch paediatric abdominopelvic CT and CTA, but technical factors such as pitch and imaging range must be considered to optimize ATPS benefits. (orig.)

  14. Effects of automatic tube potential selection on radiation dose index, image quality, and lesion detectability in pediatric abdominopelvic CT and CTA: a phantom study

    International Nuclear Information System (INIS)

    To assess the effect of automatic tube potential selection (ATPS) on radiation dose, image quality, and lesion detectability in paediatric abdominopelvic CT and CT angiography (CTA). A paediatric modular phantom with contrast inserts was examined with routine pitch (1.4) and high pitch (3.0) using a standard abdominopelvic protocol with fixed 120 kVp, and ATPS with variable kVp in non-contrast, contrast-enhanced, and CTA mode. The volume CT dose index (CTDIvol), contrast-to-noise ratio (CNR) and lesion detectability index (d') were compared between the standard protocol and ATPS examinations. CTDIvol was reduced in all routine pitch ATPS examinations, with dose reductions of 27-52 % in CTA mode (P < 0.0001), 15-33 % in contrast-enhanced mode (P = 0.0003) and 8-14 % in non-contrast mode (P = 0.03). Iodine and soft tissue insert CNR and d' were improved or maintained in all ATPS examinations. kVp and dose were reduced in 25 % of high pitch ATPS examinations and in none of the full phantom examinations obtained after a single full phantom localizer. ATPS reduces radiation dose while maintaining image quality and lesion detectability in routine pitch paediatric abdominopelvic CT and CTA, but technical factors such as pitch and imaging range must be considered to optimize ATPS benefits. (orig.)

  15. Automatic selection of the left ventricular sampling region by nuclear angiocardiography and extraction of the ejection fraction as compared with the three-region-method by hand

    International Nuclear Information System (INIS)

    A program for automatic determination of the left ventricle contour and for automatic calculation of the ejection fraction is presented. The results are comparable to those of the tedious manual evaluation procedure. Preconditions are: A suitable statistics of counting rates and a correct projection of the left ventricle without superposition of the left atrium or the right ventricle. (WU)

  16. Viability of the Happy Factor™ targeted selective treatment approach on several sheep farms in Scotland.

    Science.gov (United States)

    McBean, David; Nath, Mintu; Lambe, Nicola; Morgan-Davies, Claire; Kenyon, Fiona

    2016-03-15

    The aim of this study was to examine the use of Happy Factor™ weight based targeted selective treatment (TST) on several commercial farms in Scotland in combination with findings from a long term trial on a research farm to assess the potential for TST use in varying farming operations as an alternative to the current regimen of whole flock treatment. Lambs on each farm were regularly weighed and climatic conditions and pasture availability measured for inclusion into the Happy Factor™ model to calculate weight targets. Half of the lambs were allocated to TST treatment and any failing to reach the weight target was treated with the anthelmintic of choice on that farm, while the remaining half of each flock was treated with anthelmintic as per normal practice on that farm (routine treatment, RT). The research farm (farm 1) hosted a long term trial using four anthelmintic treatment regimes over 6 years, and data from two regimes are presented here, alongside findings from three further farms: two commercial enterprises (farms 2 and 3) and a research farm operating as a commercial analogue with two breeds (farms 4a and 4b). The effect of TST strategy on lamb productivity and the number of anthelmintic treatments was investigated. There was no evidence (p>0.300) that mean bodyweight or growth rate was different between TST and RT groups on any of the farms and 95% confidence intervals of TST and RT groups generally suggested that TST had negligible unfavourable effects on the average growth of lambs for most of the farms. Growth rates ranged from 97.39 to 189.16g/day reflecting the varied nature of the farms. All commercial farms used significantly less (1.34 RT versus 1.14 TST treatments per animal, p<0.05) anthelmintic in lambs following TST, with a reduction from 1, 1, 1.03 and 1.14 to 0.77, 0.57, 0.82 and 0.81 in the number of treatments per animal for farms 2, 3, 4a and 4b respectively. This study suggests that TST is a viable means of controlling parasitic

  17. Characterisation of aptamer-target interactions by branched selection and high-throughput sequencing of SELEX pools

    DEFF Research Database (Denmark)

    Dupont, Daniel M; Larsen, Niels; Jensen, Jan K;

    2015-01-01

    Nucleic acid aptamer selection by systematic evolution of ligands by exponential enrichment (SELEX) has shown great promise for use in the development of research tools, therapeutics and diagnostics. Typically, aptamers are identified from libraries containing up to 10(16) different RNA or DNA...... sequences by 5-10 rounds of affinity selection towards a target of interest. Such library screenings can result in complex pools of many target-binding aptamers. New high-throughput sequencing techniques may potentially revolutionise aptamer selection by allowing quantitative assessment of the dynamic...... provide detailed information about aptamer binding sites, preferences for specific target conformations, and functional effects of the aptamers. The procedure was applied on a diverse pool of 2'-fluoropyrimidine-modified RNA enriched for aptamers specific for the serpin plasminogen activator inhibitor-1...

  18. On and off-target effects of telomere uncapping G-quadruplex selective ligands based on pentacyclic acridinium salts

    OpenAIRE

    Iachettini, Sara; Stevens, Malcolm FG; Frigerio, Mark; Hummersone, Marc G; Hutchinson, Ian; Garner, Thomas P.; Searle, Mark S.; Wilson, David W; Munde, Manoj; Nanjunda, Rupesh; D’Angelo, Carmen; Zizza, Pasquale; Rizzo, Angela; Cingolani, Chiara; De Cicco, Federica

    2013-01-01

    Quadruplexes DNA are present in telomeric DNA as well as in several cancer-related gene promoters and hence affect gene expression and subsequent biological processes. The conformations of G4 provide selective recognition sites for small molecules and thus these structures have become important drug-design targets for cancer treatment. The DNA G-quadruplex binding pentacyclic acridinium salt RHPS4 (1) has many pharmacological attributes of an ideal telomere-targeting agent but has undesirable...

  19. In vitro selection of G-rich RNA aptamers that target HIV-1 integrase

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Aptamers that interact with various HIV-1 proteins,such as reverse transcriptase,Rev,Tat protein,and nuclear capsule protein,have been prepared through SELEX (systematic evolution of ligands by ex-ponential enrichment) technique. However,there are few reports about the DNA or RNA aptamers that target HIV-1 integrase. In this investigation,we selected alternative RNA aptamers specific for the HIV-1 integrase by using a different binding buffer containing 10 mmol·L-1 MgCl2 and 100 mmol·L-1 KCl. Aptamer IN1,IN2,IN3 had similar and the highest Kd values from 145 to 239 nmol·L-1. Structural studies showed that they formed similar stem-loop structure. Deletion of any stem structure resulted in diminished affinity. In addition,structure probing study with antisense DNA indicated that the stem-loop structure in the random region was critical for integrase binding. Although aptamer IN1 failed to form G-quartet structure,it might directly interact with the DDE motif of integrase,which is the virus DNA-binding site,because G-quadruplex T40214 competitively inhibited the interaction between IN1 and integrase. Together,this study generated a novel RNA aptamer IN1,which could be useful in basic research and anti-HIV drug screening.

  20. A statistical approach to selecting and confirming validation targets in -omics experiments

    Directory of Open Access Journals (Sweden)

    Leek Jeffrey T

    2012-06-01

    Full Text Available Abstract Background Genomic technologies are, by their very nature, designed for hypothesis generation. In some cases, the hypotheses that are generated require that genome scientists confirm findings about specific genes or proteins. But one major advantage of high-throughput technology is that global genetic, genomic, transcriptomic, and proteomic behaviors can be observed. Manual confirmation of every statistically significant genomic result is prohibitively expensive. This has led researchers in genomics to adopt the strategy of confirming only a handful of the most statistically significant results, a small subset chosen for biological interest, or a small random subset. But there is no standard approach for selecting and quantitatively evaluating validation targets. Results Here we present a new statistical method and approach for statistically validating lists of significant results based on confirming only a small random sample. We apply our statistical method to show that the usual practice of confirming only the most statistically significant results does not statistically validate result lists. We analyze an extensively validated RNA-sequencing experiment to show that confirming a random subset can statistically validate entire lists of significant results. Finally, we analyze multiple publicly available microarray experiments to show that statistically validating random samples can both (i provide evidence to confirm long gene lists and (ii save thousands of dollars and hundreds of hours of labor over manual validation of each significant result. Conclusions For high-throughput -omics studies, statistical validation is a cost-effective and statistically valid approach to confirming lists of significant results.

  1. Selective induction of oxidative stress in cancer cells via synergistic combinations of agents targeting redox homeostasis.

    Science.gov (United States)

    Akladios, Fady N; Andrew, Scott D; Parkinson, Christopher J

    2015-07-01

    Cancer cell resistance to chemotherapy is still a heavy burden that impairs the response of many cancer patients to conventional chemotherapy. Using drug combinations is one therapeutic approach to overcome the developing resistance to any one drug. Oxidative stress is now a generally regarded hallmark of cancer that can be one approach to selectively target cancer cells while sparing normal cells. With the aim of increasing oxidative stress in cancer cells to a lethal set point, we have generated and combined several series of redox active compounds that act at different points of the cellular oxidative cascade. The premise of such combinations is to deplete of endogenous antioxidant defence proteins (e.g., Glutathione) while concomitantly increasing the generation of ROS via metal redox recycling and Fenton chemistry which eventually leads to the disruption of cellular redox homeostasis and induction of cell death. Through this approach, we have identified highly synergistic combinations of two distinctive classes of compounds (Azines and Copper(II) complexes of 2-pyridyl ketone thiosemicarbazones) which are capable of eliminating cancer cells without concomitant increase in toxicity toward normal cells. In one of our most potent combinations, a combination index (CI) value of 0.056 was observed, representing a 17 fold enhancement in activity beyond additive effects. Such new combination regimen of redox active compounds can be one step closer to potentially safer low dose chemotherapy. PMID:26022081

  2. In vitro selection of G-rich RNA aptamers that target HIV-1 integrase

    Institute of Scientific and Technical Information of China (English)

    LIU YingChun; ZHANG Yan; YE GuoZhu; YANG ZhenJun; ZHANG LiangRen; ZHANG LiHe

    2008-01-01

    Aptamers that interact with various HIV-1 proteins, such as reverse transcriptase, Rev, Tat protein, and nuclear capsule protein, have been prepared through SELEX (systematic evolution of ligands by ex-ponential enrichment) technique. However, there are few reports about the DNA or RNA aptamers that target HIV-1 integrase. In this investigation, we selected alternative RNA aptamers specific for the HIV-1 Aptamer IN1, IN2, IN3 had similar and the highest Kd values from 145 to 239 nmol. L-1. Structural studies showed that they formed similar stem-loop structure. Deletion of any stem structure resulted in diminished affinity. In addition, structure probing study with antisense DNA indicated that the stem-loop structure in the random region was critical for integrase binding. Although aptamer IN1 failed to form G-quartet structure, it might directly interact with the DDE motif of integrase, which is the virus DNA-binding site, because G-quadruplex T40214 competitively inhibited the interaction between IN1 and integrase. Together, this study generated a novel RNA aptamer IN1, which could be useful in basic research and anti-HIV drug screening.

  3. Generation of orthogonally selective bacterial riboswitches by targeted mutagenesis and in vivo screening.

    Science.gov (United States)

    Vincent, Helen A; Robinson, Christopher J; Wu, Ming-Cheng; Dixon, Neil; Micklefield, Jason

    2014-01-01

    Riboswitches are naturally occurring RNA-based genetic switches that control gene expression in response to the binding of small-molecule ligands, typically through modulation of transcription or translation. Their simple mechanism of action and the expanding diversity of riboswitch classes make them attractive targets for the development of novel gene expression tools. The essential first step in realizing this potential is to generate artificial riboswitches that respond to nonnatural, synthetic ligands, thereby avoiding disruption of normal cellular function. Here we describe a strategy for engineering orthogonally selective riboswitches based on natural switches. The approach begins with saturation mutagenesis of the ligand-binding pocket of a naturally occurring riboswitch to generate a library of riboswitch mutants. These mutants are then screened in vivo against a synthetic compound library to identify functional riboswitch-ligand combinations. Promising riboswitch-ligand pairs are then further characterized both in vivo and in vitro. Using this method, a series of artificial riboswitches can be generated that are versatile synthetic biology tools for use in protein production, gene functional analysis, metabolic engineering, and other biotechnological applications. PMID:24549615

  4. Ken & barbie selectively regulates the expression of a subset of Jak/STAT pathway target genes.

    Science.gov (United States)

    Arbouzova, Natalia I; Bach, Erika A; Zeidler, Martin P

    2006-01-10

    A limited number of evolutionarily conserved signal transduction pathways are repeatedly reused during development to regulate a wide range of processes. Here we describe a new negative regulator of JAK/STAT signaling and identify a potential mechanism by which the pleiotropy of responses resulting from pathway activation is generated in vivo. As part of a genetic interaction screen, we have identified Ken & Barbie (Ken) , which is an ortholog of the mammalian proto-oncogene BCL6 , as a negative regulator of the JAK/STAT pathway. Ken genetically interacts with the pathway in vivo and recognizes a DNA consensus sequence overlapping that of STAT92E in vitro. Tissue culture-based assays demonstrate the existence of Ken-sensitive and Ken-insensitive STAT92E binding sites, while ectopically expressed Ken is sufficient to downregulate a subset of JAK/STAT pathway target genes in vivo. Finally, we show that endogenous Ken specifically represses JAK/STAT-dependent expression of ventral veins lacking (vvl) in the posterior spiracles. Ken therefore represents a novel regulator of JAK/STAT signaling whose dynamic spatial and temporal expression is capable of selectively modulating the transcriptional repertoire elicited by activated STAT92E in vivo. PMID:16401426

  5. Green tea extract selectively targets nanomechanics of live metastatic cancer cells

    International Nuclear Information System (INIS)

    Green tea extract (GTE) is known to be a potential anticancer agent (Yang et al 2009 Nat. Rev. Cancer 9 429-39) with various biological activities (Lu et al 2005 Clin. Cancer Res. 11 1675-83; Yang et al 1998 Carcinogenesis 19 611-6) yet the precise mechanism of action is still unclear. The biomechanical response of GTE treated cells taken directly from patient's body samples was measured using atomic force microscopy (AFM) (Binnig et al 1986 Phys. Rev. Lett. 56 930). We found significant increase in stiffness of GTE treated metastatic tumor cells, with a resulting value similar to untreated normal mesothelial cells, whereas mesothelial cell stiffness after GTE treatment is unchanged. Immunofluorescence analysis showed an increase in cytoskeletal-F-actin in GTE treated tumor cells, suggesting GTE treated tumor cells display mechanical, structural and morphological features similar to normal cells, which appears to be mediated by annexin-I expression, as determined by siRNA analysis of an in vitro cell line model. Our data indicates that GTE selectively targets human metastatic cancer cells but not normal mesothelial cells, a finding that is significantly advantageous compared to conventional chemotherapy agents.

  6. Green tea extract selectively targets nanomechanics of live metastatic cancer cells

    Science.gov (United States)

    Cross, Sarah E.; Jin, Yu-Sheng; Lu, Qing-Yi; Rao, JianYu; Gimzewski, James K.

    2011-05-01

    Green tea extract (GTE) is known to be a potential anticancer agent (Yang et al 2009 Nat. Rev. Cancer 9 429-39) with various biological activities (Lu et al 2005 Clin. Cancer Res. 11 1675-83 Yang et al 1998 Carcinogenesis 19 611-6) yet the precise mechanism of action is still unclear. The biomechanical response of GTE treated cells taken directly from patient's body samples was measured using atomic force microscopy (AFM) (Binnig et al 1986 Phys. Rev. Lett. 56 930). We found significant increase in stiffness of GTE treated metastatic tumor cells, with a resulting value similar to untreated normal mesothelial cells, whereas mesothelial cell stiffness after GTE treatment is unchanged. Immunofluorescence analysis showed an increase in cytoskeletal-F-actin in GTE treated tumor cells, suggesting GTE treated tumor cells display mechanical, structural and morphological features similar to normal cells, which appears to be mediated by annexin-I expression, as determined by siRNA analysis of an in vitro cell line model. Our data indicates that GTE selectively targets human metastatic cancer cells but not normal mesothelial cells, a finding that is significantly advantageous compared to conventional chemotherapy agents.

  7. Receptor-Bound Targets of Selective Autophagy Use a Scaffold Protein to Activate the Atg1 Kinase.

    Science.gov (United States)

    Kamber, Roarke A; Shoemaker, Christopher J; Denic, Vladimir

    2015-08-01

    Selective autophagy eliminates protein aggregates, damaged organelles, and other targets that otherwise accumulate and cause disease. Autophagy receptors mediate selectivity by connecting targets to the autophagosome membrane. It has remained unknown whether receptors perform additional functions. Here, we show that in yeast certain receptor-bound targets activate Atg1, the kinase that controls autophagosome formation. Specifically, we found that in nutrient-rich conditions, Atg1 is active only in a multisubunit complex comprising constitutive protein aggregates, their autophagy receptor, and a scaffold protein, Atg11. Development of a cell-free assay for Atg1-mediated phosphorylation enabled us to activate Atg1 with purified receptor-bound aggregates and Atg11. Another target, damaged peroxisomes, also activated Atg1 using Atg11 with a distinct receptor. Our work reveals that receptor-target complexes activate Atg1 to drive formation of selective autophagosomes. This regulatory logic is a key similarity between selective autophagy and bulk autophagy, which is initiated by a distinct Atg1 activation mechanism during starvation. PMID:26166702

  8. New Strategies for the Next Generation of Matrix-Metalloproteinase Inhibitors: Selectively Targeting Membrane-Anchored MMPs with Therapeutic Antibodies

    Directory of Open Access Journals (Sweden)

    Laetitia Devy

    2011-01-01

    Full Text Available MMP intervention strategies have met with limited clinical success due to severe toxicities. In particular, treatment with broad-spectrum MMP-inhibitors (MMPIs caused musculoskeletal pain and inflammation. Selectivity may be essential for realizing the clinical potential of MMPIs. Here we review discoveries pinpointing membrane-bound MMPs as mediators of mechanisms underlying cancer and inflammation and as possible therapeutic targets for prevention/treatment of these diseases. We discuss strategies to target these therapeutic proteases using highly selective inhibitory agents (i.e., human blocking antibodies against individual membrane-bound MMPs.

  9. SDSS-III Baryon Oscillation Spectroscopic Survey Data Release 12: galaxy target selection and large scale structure catalogues

    CERN Document Server

    Reid, Beth; Padmanabhan, Nikhil; Percival, Will J; Tinker, Jeremy; Tojeiro, Rita; White, Martin; Eisenstein, Daniel J; Maraston, Claudia; Ross, Ashley J; Sanchez, Ariel G; Schlegel, David; Sheldon, Erin; Strauss, Michael A; Thomas, Daniel; Wake, David; Beutler, Florian; Bizyaev, Dmitry; Bolton, Adam S; Brownstein, Joel R; Chuang, Chia-Hsun; Dawson, Kyle; Harding, Paul; Kitaura, Francisco-Shu; Leauthaud, Alexie; Masters, Karen; McBride, Cameron K; More, Surhud; Olmstead, Matthew D; Oravetz, Daniel; Nuza, Sebastian E; Pan, Kaike; Parejko, John; Pforr, Janine; Prada, Francisco; Rodriguez-Torres, Sergio; Salazar-Albornoz, Salvador; Samushia, Lado; Schneider, Donald P; Scoccola, Claudia G; Simmons, Audrey; Vargas-Magana, Mariana

    2015-01-01

    The Baryon Oscillation Spectroscopic Survey (BOSS), part of the Sloan Digital Sky Survey (SDSS) III project, has provided the largest survey of galaxy redshifts available to date, in terms of both the number of galaxy redshifts measured by a single survey, and the effective cosmological volume covered. Key to analysing the clustering of these data to provide cosmological measurements is understanding the detailed properties of this sample. Potential issues include variations in the target catalogue caused by changes either in the targeting algorithm or properties of the data used, the pattern of spectroscopic observations, the spatial distribution of targets for which redshifts were not obtained, and variations in the target sky density due to observational systematics. We document here the target selection algorithms used to create the galaxy samples that comprise BOSS. We also present the algorithms used to create large scale structure catalogues for the final Data Release (DR12) samples and the associated ...

  10. Metformin selectively targets cancer stem cells, and acts together with chemotherapy to block tumor growth and prolong remission

    OpenAIRE

    Hirsch, Heather A; Iliopoulos, Dimitrios; Tsichlis, Philip N.; Struhl, Kevin

    2009-01-01

    The cancer stem cell hypothesis suggests that, unlike most cancer cells within a tumor, cancer stem cells resist chemotherapeutic drugs and can regenerate the various cell types in the tumor, thereby causing relapse of the disease. Thus, drugs that selectively target cancer stem cells offer great promise for cancer treatment, particularly in combination with chemotherapy. Here, we show that low doses of metformin, a standard drug for diabetes, inhibits cellular transformation and selectively ...

  11. An N-sulfanylethylanilide-based traceable linker for enrichment and selective labelling of target proteins.

    Science.gov (United States)

    Morisaki, Takuya; Denda, Masaya; Yamamoto, Jun; Tsuji, Daisuke; Inokuma, Tsubasa; Itoh, Kohji; Shigenaga, Akira; Otaka, Akira

    2016-05-25

    An N-sulfanylethylanilide-based traceable linker, developed to facilitate identification of target proteins of bioactive compounds, was introduced into an alkynylated target protein. Subsequent adsorption onto streptavidin beads allowed it to be treated with a cysteine-fluorophore conjugate in the presence of phosphate. This induced the N-S acyl transfer reaction of the N-sulfanylethylanilide unit. The subsequent native chemical ligation of the fluorophore resulted in cleavage of the linker for target elution and fluorescence labelling of the target, allowing it to be distinguished from non-target proteins. PMID:27146590

  12. Semantic Priming from Letter-Searched Primes Occurs for Low- but Not High-Frequency Targets: Automatic Semantic Access May Not Be a Myth

    Science.gov (United States)

    Tse, Chi-Shing; Neely, James H.

    2007-01-01

    Letter-search (LS) within a prime often eliminates semantic priming. In 2 lexical decision experiments, the authors found that priming from LS primes occurred for low-frequency (LF) but not high-frequency (HF) targets whether the target's word frequency was manipulated between or within participants and whether the prime-target pairs were…

  13. From Target Selection to Post-Stimulation Analysis: Example of an Unconventional Faulted Reservoir

    Science.gov (United States)

    LeCalvez, J. H.; Williams, M.; Xu, W.; Stokes, J.; Moros, H.; Maxwell, S. C.; Conners, S.

    2011-12-01

    As the global balance of supply and demand forces the hydrocarbon industry toward unconventional resources, technology- and economics-driven shale oil and gas production is gaining momentum throughout many basins worldwide. Production from such unconventional plays is facilitated by massive hydraulic fracturing treatments aimed at increasing permeability and reactivating natural fractures. Large-scale faulting and fracturing partly control stress distribution, hence stimulation-derived hydraulically-induced fracture systems development. Therefore, careful integrated approaches to target selection, treatment staging, and stimulation methods need to be used to economically maximize ultimate hydrocarbon recovery. We present a case study of a multistage, multilateral stimulation project in the Fort Worth Basin, Texas. Wells had to be drilled within city limits in a commercially developing building area. Well locations and trajectories were determined in and around large-scale faults using 3D surface seismic with throws varying from seven to thirty meters. As a result, three horizontal wells were drilled in the Lower Barnett Shale section, 150 m apart with the central well landed about 25 m shallower than the outside laterals. Surface seismic indicates that the surface locations are on top of a major fault complex with the lateral sections drilling away from the major fault system and through a smaller fault. Modeling of the borehole-based microseismic monitoring options led to the selection of an optimum set of configurations given the operational restrictions faced: monitoring would mainly take place using a horizontal array to be tractored downhole and moved according to the well and stage to be monitored. Wells were completed using a perf-and-plug approach allowing for each stimulation stage to obtain a precise orientation of the various three-component accelerometers of the monitoring array as well as the calibration of the velocity model used to process the

  14. SynLethDB: synthetic lethality database toward discovery of selective and sensitive anticancer drug targets.

    Science.gov (United States)

    Guo, Jing; Liu, Hui; Zheng, Jie

    2016-01-01

    Synthetic lethality (SL) is a type of genetic interaction between two genes such that simultaneous perturbations of the two genes result in cell death or a dramatic decrease of cell viability, while a perturbation of either gene alone is not lethal. SL reflects the biologically endogenous difference between cancer cells and normal cells, and thus the inhibition of SL partners of genes with cancer-specific mutations could selectively kill cancer cells but spare normal cells. Therefore, SL is emerging as a promising anticancer strategy that could potentially overcome the drawbacks of traditional chemotherapies by reducing severe side effects. Researchers have developed experimental technologies and computational prediction methods to identify SL gene pairs on human and a few model species. However, there has not been a comprehensive database dedicated to collecting SL pairs and related knowledge. In this paper, we propose a comprehensive database, SynLethDB (http://histone.sce.ntu.edu.sg/SynLethDB/), which contains SL pairs collected from biochemical assays, other related databases, computational predictions and text mining results on human and four model species, i.e. mouse, fruit fly, worm and yeast. For each SL pair, a confidence score was calculated by integrating individual scores derived from different evidence sources. We also developed a statistical analysis module to estimate the druggability and sensitivity of cancer cells upon drug treatments targeting human SL partners, based on large-scale genomic data, gene expression profiles and drug sensitivity profiles on more than 1000 cancer cell lines. To help users access and mine the wealth of the data, we developed other practical functionalities, such as search and filtering, orthology search, gene set enrichment analysis. Furthermore, a user-friendly web interface has been implemented to facilitate data analysis and interpretation. With the integrated data sets and analytics functionalities, SynLethDB would

  15. HELIOSEISMOLOGY OF PRE-EMERGING ACTIVE REGIONS. I. OVERVIEW, DATA, AND TARGET SELECTION CRITERIA

    International Nuclear Information System (INIS)

    This first paper in a series describes the design of a study testing whether pre-appearance signatures of solar magnetic active regions were detectable using various tools of local helioseismology. The ultimate goal is to understand flux-emergence mechanisms by setting observational constraints on pre-appearance subsurface changes, for comparison with results from simulation efforts. This first paper provides details of the data selection and preparation of the samples, each containing over 100 members, of two populations: regions on the Sun that produced a numbered NOAA active region, and a 'control' sample of areas that did not. The seismology is performed on data from the GONG network; accompanying magnetic data from SOHO/MDI are used for co-temporal analysis of the surface magnetic field. Samples are drawn from 2001-2007, and each target is analyzed for 27.7 hr prior to an objectively determined time of emergence. The results of two analysis approaches are published separately: one based on averages of the seismology- and magnetic-derived signals over the samples, another based on Discriminant Analysis of these signals, for a statistical test of detectable differences between the two populations. We include here descriptions of a new potential-field calculation approach and the algorithm for matching sample distributions over multiple variables. We describe known sources of bias and the approaches used to mitigate them. We also describe unexpected bias sources uncovered during the course of the study and include a discussion of refinements that should be included in future work on this topic.

  16. Efficacy Trial of a Selective Prevention Program Targeting Both Eating Disorder Symptoms and Unhealthy Weight Gain among Female College Students

    Science.gov (United States)

    Stice, Eric; Rohde, Paul; Shaw, Heather; Marti, C. Nathan

    2012-01-01

    Objective: Evaluate a selective prevention program targeting both eating disorder symptoms and unhealthy weight gain in young women. Method: Female college students at high-risk for these outcomes by virtue of body image concerns (N = 398; M age = 18.4 years, SD = 0.6) were randomized to the Healthy Weight group-based 4-hr prevention program,…

  17. Free ion selective radionuclide extraction (FISRE) and the targeting potential of theranostic radio-complexes

    International Nuclear Information System (INIS)

    The present paper briefly discusses molecular targeting, receptors, and distribution, all set in the context of the use of radiolabelled and chelated peptides in peptide receptor scintigraphy (PRS) and peptide radionuclide therapy (PRRT). The discussion further addresses the potential of compartmental modelling as a tool in optimization approaches for targeting complexes. The latter point is illustrated by the use of FISRE-methods and clinical data on 177Lu-DOTA-Tyr3-octreotate in a preliminary modelling trial, to show the principal relevance of various complex properties for targeting characteristics in optimization exercises. The results indicate that improving the complex dynamic stability may mimic improved complex targeting potential. (author)

  18. Acquisitions as lotteries? : The selection of target-firm risk and its impact on merger outcomes

    NARCIS (Netherlands)

    Schneider, Christoph; Spalt, Oliver

    2017-01-01

    From 1987 to 2008, riskier firms were more likely to be taken over. Yet, on average, the acquirer declined in value by 2.8% when it bought a "risky target" (the third tercile, having an annualized idiosyncratic volatility of 61% or more), but only by 0.6% when it bought a "safe target" (the first te

  19. Electronic amplifiers for automatic compensators

    CERN Document Server

    Polonnikov, D Ye

    1965-01-01

    Electronic Amplifiers for Automatic Compensators presents the design and operation of electronic amplifiers for use in automatic control and measuring systems. This book is composed of eight chapters that consider the problems of constructing input and output circuits of amplifiers, suppression of interference and ensuring high sensitivity.This work begins with a survey of the operating principles of electronic amplifiers in automatic compensator systems. The succeeding chapters deal with circuit selection and the calculation and determination of the principal characteristics of amplifiers, as

  20. Selection of Novel Peptides Homing the 4T1 CELL Line: Exploring Alternative Targets for Triple Negative Breast Cancer.

    Science.gov (United States)

    Silva, Vera L; Ferreira, Debora; Nobrega, Franklin L; Martins, Ivone M; Kluskens, Leon D; Rodrigues, Ligia R

    2016-01-01

    The use of bacteriophages to select novel ligands has been widely explored for cancer therapy. Their application is most warranted in cancer subtypes lacking knowledge on how to target the cancer cells in question, such as the triple negative breast cancer, eventually leading to the development of alternative nanomedicines for cancer therapeutics. Therefore, the following study aimed to select and characterize novel peptides for a triple negative breast cancer murine mammary carcinoma cell line- 4T1. Using phage display, 7 and 12 amino acid random peptide libraries were screened against the 4T1 cell line. A total of four rounds, plus a counter-selection round using the 3T3 murine fibroblast cell line, was performed. The enriched selective peptides were characterized and their binding capacity towards 4T1 tissue samples was confirmed by immunofluorescence and flow cytometry analysis. The selected peptides (4T1pep1 -CPTASNTSC and 4T1pep2-EVQSSKFPAHVS) were enriched over few rounds of selection and exhibited specific binding to the 4T1 cell line. Interestingly, affinity to the human MDA-MB-231 cell line was also observed for both peptides, promoting the translational application of these novel ligands between species. Additionally, bioinformatics analysis suggested that both peptides target human Mucin-16. This protein has been implicated in different types of cancer, as it is involved in many important cellular functions. This study strongly supports the need of finding alternative targeting systems for TNBC and the peptides herein selected exhibit promising future application as novel homing peptides for breast cancer therapy. PMID:27548261

  1. Comparing the Selection and Placement of Best Management Practices in Improving Water Quality Using a Multiobjective Optimization and Targeting Method

    Directory of Open Access Journals (Sweden)

    Li-Chi Chiang

    2014-03-01

    Full Text Available Suites of Best Management Practices (BMPs are usually selected to be economically and environmentally efficient in reducing nonpoint source (NPS pollutants from agricultural areas in a watershed. The objective of this research was to compare the selection and placement of BMPs in a pasture-dominated watershed using multiobjective optimization and targeting methods. Two objective functions were used in the optimization process, which minimize pollutant losses and the BMP placement areas. The optimization tool was an integration of a multi-objective genetic algorithm (GA and a watershed model (Soil and Water Assessment Tool—SWAT. For the targeting method, an optimum BMP option was implemented in critical areas in the watershed that contribute the greatest pollutant losses. A total of 171 BMP combinations, which consist of grazing management, vegetated filter strips (VFS, and poultry litter applications were considered. The results showed that the optimization is less effective when vegetated filter strips (VFS are not considered, and it requires much longer computation times than the targeting method to search for optimum BMPs. Although the targeting method is effective in selecting and placing an optimum BMP, larger areas are needed for BMP implementation to achieve the same pollutant reductions as the optimization method.

  2. Targeting hunter distribution based on host resource selection and kill sites to manage disease risk

    DEFF Research Database (Denmark)

    Dugal, Cherie; van Beest, Floris; Vander Wal, Eric;

    2013-01-01

    Endemic and emerging diseases are rarely uniform in their spatial distribution or prevalence among cohorts of wildlife. Spatial models that quantify risk-driven differences in resource selection and hunter mortality of animals at fine spatial scales can assist disease management by identifying high......-risk areas and individuals. We used resource selection functions (RSFs) and selection ratios (SRs) to quantify sex- and age-specific resource selection patterns of collared (n = 67) and hunter-killed (n = 796) nonmigratory elk (Cervus canadensis manitobensis) during the hunting season between 2002 and 2012...... disease) rarely selected for sites outside of parks during the hunting season in contrast to adult females and juvenile males. The RSFs showed selection by adult females and juvenile males to be negatively associated with landscape-level forest cover, high road density, and water cover, whereas hunter...

  3. Using automatic programming for simulating reliability network models

    Science.gov (United States)

    Tseng, Fan T.; Schroer, Bernard J.; Zhang, S. X.; Wolfsberger, John W.

    1988-01-01

    This paper presents the development of an automatic programming system for assisting modelers of reliability networks to define problems and then automatically generate the corresponding code in the target simulation language GPSS/PC.

  4. Economic assessment of FEC-based targeted selective drenching in horses.

    Science.gov (United States)

    Sallé, Guillaume; Cortet, Jacques; Koch, Christine; Reigner, Fabrice; Cabaret, Jacques

    2015-11-30

    In the face of an increased prevalence of drug-resistant cyathostomin populations, a targeted selective treatment (TST) strategy based on Faecal Egg Counts (FECs) has been proposed as an alternative management strategy. However, associated costs may be a barrier to the uptake of this strategy. Our study aims to provide an economic assessment of FEC-based TST. FECs were determined in a Welsh pony herd thrice a year from 2010 to 2014. This database was used to explore the impact of FEC price, sampling strategy (individual or pooled) and labour-associated costs. Drug price was set at the cheapest level, hence providing a conservative framework to determine the maximum viable FEC price in the context of a cost-driven horse industry. The maximum viable FEC price for a cost-efficient individual based strategy was determined by an in silico bootstrap approach consisting of randomly sampling 1000 virtual pony herds of various sizes (1 to 100 ponies) from the available database and estimating the associated costs (FEC price ranging from € 1 to € 10, anthelmintic costs and labour-associated costs). The costs and benefits of the pooling strategy that consists of basing the decision to treat on group FEC values were also investigated. This is thought to reduce FEC-based costs but may result in highly infected individuals being left undrenched, i.e. in false-negatives, as a result of FEC overdispersion. For various pool-sizes (1-20 ponies) and various cut-off thresholds (50-200 eggs/g), we sampled 1000 pony herds in silico to estimate the associated costs and determine the number of positive ponies within a negative pool. Following these simulations, pool-based FECs of various sizes were performed on 40 ponies to compare predictions with real data. Within 4 years, anthelmintic costs were cut by 80%, albeit with free FECs. In silico estimations suggested that an individual FEC-based TST would not be cost-efficient in this context for an FEC price above € 5. With a pooled

  5. Target-selective homologous recombination cloning for high-throughput generation of monoclonal antibodies from single plasma cells

    OpenAIRE

    Isobe Masaharu; Yoshioka Megumi; Kurosawa Nobuyuki

    2011-01-01

    Abstract Background Molecular cloning of functional immunoglobulin genes from single plasma cells is one of the most promising technologies for the rapid development of monoclonal antibody drugs. However, the proper insertion of PCR-amplified immunoglobulin genes into expression vectors remains an obstacle to the high-throughput production of recombinant monoclonal antibodies. Results We developed a single-step cloning method, target-selective homologous recombination (TS-HR), in which PCR-am...

  6. Animal models for medications development targeting alcohol abuse using selectively bred rat lines: Neurobiological and pharmacological validity

    OpenAIRE

    Bell, Richard L.; Sable, Helen J. K.; Colombo, Giancarlo; Hyytia, Petri; Rodd, Zachary A.; Lumeng, Lawrence

    2012-01-01

    The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models f...

  7. Selective recognition and stabilization of new ligands targeting the potassium form of the human telomeric G-quadruplex DNA

    Science.gov (United States)

    Lin, Yi-Hwa; Chuang, Show-Mei; Wu, Pei-Ching; Chen, Chun-Liang; Jeyachandran, Sivakamavalli; Lo, Shou-Chen; Huang, Hsu-Shan; Hou, Ming-Hon

    2016-01-01

    The development of a ligand that is capable of distinguishing among the wide variety of G-quadruplex structures and targeting telomeres to treat cancer is particularly challenging. In this study, the ability of two anthraquinone telomerase inhibitors (NSC749235 and NSC764638) to target telomeric G-quadruplex DNA was probed. We found that these ligands specifically target the potassium form of telomeric G-quadruplex DNA over the DNA counterpart. The characteristic interaction with the telomeric G-quadruplex DNA and the anticancer activities of these ligands were also explored. The results of this present work emphasize our understanding of the binding selectivity of anthraquinone derivatives to G-quadruplex DNA and assists in future drug development for G-quadruplex-specific ligands. PMID:27511133

  8. K-targeted metabolomic analysis extends chemical subtraction to DESIGNER extracts: selective depletion of extracts of hops (Humulus lupulus).

    Science.gov (United States)

    Ramos Alvarenga, René F; Friesen, J Brent; Nikolić, Dejan; Simmler, Charlotte; Napolitano, José G; van Breemen, Richard; Lankin, David C; McAlpine, James B; Pauli, Guido F; Chen, Shao-Nong

    2014-12-26

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid-liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGNER extract = total extract ± target compound(s). Expanding the scope of the recently reported depletion of extracts by immunoaffinity or solid phase liquid chromatography, the present approach allows a more flexible, single- or multi-targeted removal of constituents from complex extracts such as botanicals. Chemical subtraction enables both chemical and biological characterization, including detection of synergism/antagonism by both the subtracted targets and the remaining metabolite mixture, as well as definition of the residual complexity of all fractions. The feasibility of the DESIGNER concept is shown by K-targeted subtraction of four bioactive prenylated phenols, isoxanthohumol (1), 8-prenylnaringenin (2), 6-prenylnaringenin (3), and xanthohumol (4), from a standardized hops (Humulus lupulus L.) extract using specific solvent systems. Conversely, adding K-targeted isolates allows enrichment of the original extract and hence provides an augmented DESIGNER material. Multiple countercurrent separation steps were used to purify each of the four compounds, and four DESIGNER extracts with varying depletions were prepared. The DESIGNER approach innovates the characterization of chemically complex extracts through integration of enabling technologies such as countercurrent separation, K-by-bioactivity, the residual complexity concepts, as well as quantitative analysis by (1)H NMR, LC-MS, and HiFSA-based NMR fingerprinting. PMID:25437744

  9. PLS-Based and Regularization-Based Methods for the Selection of Relevant Variables in Non-targeted Metabolomics Data.

    Science.gov (United States)

    Bujak, Renata; Daghir-Wojtkowiak, Emilia; Kaliszan, Roman; Markuszewski, Michał J

    2016-01-01

    Non-targeted metabolomics constitutes a part of the systems biology and aims at determining numerous metabolites in complex biological samples. Datasets obtained in the non-targeted metabolomics studies are high-dimensional due to sensitivity of mass spectrometry-based detection methods as well as complexity of biological matrices. Therefore, a proper selection of variables which contribute into group classification is a crucial step, especially in metabolomics studies which are focused on searching for disease biomarker candidates. In the present study, three different statistical approaches were tested using two metabolomics datasets (RH and PH study). The orthogonal projections to latent structures-discriminant analysis (OPLS-DA) without and with multiple testing correction as well as the least absolute shrinkage and selection operator (LASSO) with bootstrapping, were tested and compared. For the RH study, OPLS-DA model built without multiple testing correction selected 46 and 218 variables based on the VIP criteria using Pareto and UV scaling, respectively. For the PH study, 217 and 320 variables were selected based on the VIP criteria using Pareto and UV scaling, respectively. In the RH study, OPLS-DA model built after correcting for multiple testing, selected 4 and 19 variables as in terms of Pareto and UV scaling, respectively. For the PH study, 14 and 18 variables were selected based on the VIP criteria in terms of Pareto and UV scaling, respectively. In the RH and PH study, the LASSO selected 14 and 4 variables with reproducibility between 99.3 and 100%, respectively. In the light of PLS-based models, the larger the search space the higher the probability of developing models that fit the training data well with simultaneous poor predictive performance on the validation set. The LASSO offers potential improvements over standard linear regression due to the presence of the constrain, which promotes sparse solutions. This paper is the first one to date

  10. Target-selectivity of parvalbumin-positive interneurons in layer II of medial entorhinal cortex in normal and epileptic animals.

    Science.gov (United States)

    Armstrong, Caren; Wang, Jessica; Yeun Lee, Soo; Broderick, John; Bezaire, Marianne J; Lee, Sang-Hun; Soltesz, Ivan

    2016-06-01

    The medial entorhinal cortex layer II (MEClayerII ) is a brain region critical for spatial navigation and memory, and it also demonstrates a number of changes in patients with, and animal models of, temporal lobe epilepsy (TLE). Prior studies of GABAergic microcircuitry in MEClayerII revealed that cholecystokinin-containing basket cells (CCKBCs) select their targets on the basis of the long-range projection pattern of the postsynaptic principal cell. Specifically, CCKBCs largely avoid reelin-containing principal cells that form the perforant path to the ipsilateral dentate gyrus and preferentially innervate non-perforant path forming calbindin-containing principal cells. We investigated whether parvalbumin containing basket cells (PVBCs), the other major perisomatic targeting GABAergic cell population, demonstrate similar postsynaptic target selectivity as well. In addition, we tested the hypothesis that the functional or anatomic arrangement of circuit selectivity is disrupted in MEClayerII in chronic TLE, using the repeated low-dose kainate model in rats. In control animals, we found that PVBCs innervated both principal cell populations, but also had significant selectivity for calbindin-containing principal cells in MEClayerII . However, the magnitude of this preference was smaller than for CCKBCs. In addition, axonal tracing and paired recordings showed that individual PVBCs were capable of contacting both calbindin and reelin-containing principal cells. In chronically epileptic animals, we found that the intrinsic properties of the two principal cell populations, the GABAergic perisomatic bouton numbers, and selectivity of the CCKBCs and PVBCs remained remarkably constant in MEClayerII . However, miniature IPSC frequency was decreased in epilepsy, and paired recordings revealed the presence of direct excitatory connections between principal cells in the MEClayerII in epilepsy, which is unusual in normal adult MEClayerII . Taken together, these findings advance

  11. The use of selective volatization in the separation of 68Ge from irradiated Ga targets

    International Nuclear Information System (INIS)

    Cyclotron-produced 68Ge can be separated from its Ga target material by dissolving the target in aqua regia and collecting the volatile 68Ge in a solution containing 1.0 M NaOH and 2% Na2SO3. The solution is then acidified with HF before being loaded onto a column containing AG MP-1 anion exchange resin. The column is rinsed with dilute HF to remove any remaining impurities, before eluting the desired product with 0.1 M HCl. A radiochemically pure product is obtained.

  12. A Phase I Trial of Preoperative Partial Breast Radiotherapy: Patient Selection, Target Delineation, and Dose Delivery

    Science.gov (United States)

    Blitzblau, Rachel C.; Arya, Ritu; Yoo, Sua; Baker, Jay A.; Chang, Zheng; Palta, Manisha; Duffy, Eileen; Horton, Janet K.

    2015-01-01

    Purpose Diffusion of accelerated partial breast irradiation (APBI) into clinical practice is limited by the need for specialized equipment and training. The accessible external beam technique yields unacceptable complication rates, likely due to large post-operative target volumes. We designed a phase I trial evaluating preoperative radiotherapy to the intact tumor utilizing widely available technology. Methods Patients received 15, 18, or 21Gy in a single fraction to the breast tumor plus margin. Magnetic resonance imaging (MRI) was used in conjunction with standard computed tomography (CT)-based planning to identify contrast enhancing tumor. Skin markers and an intra-tumor biopsy marker were utilized for verification during treatment. Results MRI imaging was critical for target delineation as not all breast tumors were reliably identified on CT scan. Breast shape differences were consistently seen between CT and MRI but did not impede image registration or tumor identification. Target volumes were markedly smaller than historical post-operative volumes and normal tissue constraints were easily met. A biopsy marker within the breast proved sufficient for set up localization. Conclusions This single fraction linear-accelerator based ABPI approach can be easily incorporated at most treatment centers. In vivo targeting may improve accuracy and can reduce the dose to normal tissues. PMID:25834942

  13. 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

    when using zoom, but total pointing times were shorter using zoom. Furthermore, participants perceived magnification as more fatiguing than zoom. The higher accuracy of magnification makes it preferable when interacting with small targets. Our findings may guide the development of interface tools to...

  14. SDSS-III Baryon Oscillation Spectroscopic Survey Data Release 12: galaxy target selection and large-scale structure catalogues

    Science.gov (United States)

    Reid, Beth; Ho, Shirley; Padmanabhan, Nikhil; Percival, Will J.; Tinker, Jeremy; Tojeiro, Rita; White, Martin; Eisenstein, Daniel J.; Maraston, Claudia; Ross, Ashley J.; Sánchez, Ariel G.; Schlegel, David; Sheldon, Erin; Strauss, Michael A.; Thomas, Daniel; Wake, David; Beutler, Florian; Bizyaev, Dmitry; Bolton, Adam S.; Brownstein, Joel R.; Chuang, Chia-Hsun; Dawson, Kyle; Harding, Paul; Kitaura, Francisco-Shu; Leauthaud, Alexie; Masters, Karen; McBride, Cameron K.; More, Surhud; Olmstead, Matthew D.; Oravetz, Daniel; Nuza, Sebastián E.; Pan, Kaike; Parejko, John; Pforr, Janine; Prada, Francisco; Rodríguez-Torres, Sergio; Salazar-Albornoz, Salvador; Samushia, Lado; Schneider, Donald P.; Scóccola, Claudia G.; Simmons, Audrey; Vargas-Magana, Mariana

    2016-01-01

    The Baryon Oscillation Spectroscopic Survey (BOSS), part of the Sloan Digital Sky Survey (SDSS) III project, has provided the largest survey of galaxy redshifts available to date, in terms of both the number of galaxy redshifts measured by a single survey, and the effective cosmological volume covered. Key to analysing the clustering of these data to provide cosmological measurements is understanding the detailed properties of this sample. Potential issues include variations in the target catalogue caused by changes either in the targeting algorithm or properties of the data used, the pattern of spectroscopic observations, the spatial distribution of targets for which redshifts were not obtained, and variations in the target sky density due to observational systematics. We document here the target selection algorithms used to create the galaxy samples that comprise BOSS. We also present the algorithms used to create large-scale structure catalogues for the final Data Release (DR12) samples and the associated random catalogues that quantify the survey mask. The algorithms are an evolution of those used by the BOSS team to construct catalogues from earlier data, and have been designed to accurately quantify the galaxy sample. The code used, designated MKSAMPLE, is released with this paper.

  15. The selectivity of the gill-nets used to target hake ( Merluccius merluccius ) in the Cornish and Irish offshore fisheries

    DEFF Research Database (Denmark)

    Revill, A.; Cotter, J.; Armstrong, M.;

    2007-01-01

    The North European gill-net fishery targeting hake (Merluccius merluccius) is mostly prosecuted using gill-nets with a mesh size of 120 mm. Fishers from both the UK and Ireland are active in this fishery using this particular gear type. A study was undertaken aboard a commercial gill-netter off the...... coast of Cornwall (UK) in 2005 to estimate the selectivity parameters of this particular fishing gear, as little published information was available. We found that the 120 mm gill-net caught mostly larger hake, catching few fish below 60 cm. The modal selectivity length for hake using gill-nets with...... this mesh size was close to 80 cm. The study indicates that the 120 mm gill-fishery off Cornwall and Ireland is a highly size-selective component of the international fishery exploiting the northern hake stock, a stock in which international landings at length peaked at around 30 cm (2004)....

  16. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    Science.gov (United States)

    Di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-01-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation. PMID:26567894

  17. Structure-based drug design targeting the cell membrane receptor GPBAR1: exploiting the bile acid scaffold towards selective agonism

    Science.gov (United States)

    di Leva, Francesco Saverio; Festa, Carmen; Renga, Barbara; Sepe, Valentina; Novellino, Ettore; Fiorucci, Stefano; Zampella, Angela; Limongelli, Vittorio

    2015-11-01

    Bile acids can regulate nutrient metabolism through the activation of the cell membrane receptor GPBAR1 and the nuclear receptor FXR. Developing an exogenous control over these receptors represents an attractive strategy for the treatment of enterohepatic and metabolic disorders. A number of dual GPBAR1/FXR agonists are known, however their therapeutic use is limited by multiple unwanted effects due to activation of the diverse downstream signals controlled by the two receptors. On the other hand, designing selective GPBAR1 and FXR agonists is challenging since the two proteins share similar structural requisites for ligand binding. Here, taking advantage of our knowledge of the two targets, we have identified through a rational drug design study a series of amine lithocholic acid derivatives as selective GPBAR1 agonists. The presence of the 3α-NH2 group on the steroidal scaffold is responsible for the selectivity over FXR unveiling unprecedented structural insights into bile acid receptors activity modulation.

  18. Automatic derivation of domain terms and concept location based on the analysis of the identifiers

    OpenAIRE

    Vaclavik, Peter; Poruban, Jaroslav; Mezei, Marek

    2010-01-01

    Developers express the meaning of the domain ideas in specifically selected identifiers and comments that form the target implemented code. Software maintenance requires knowledge and understanding of the encoded ideas. This paper presents a way how to create automatically domain vocabulary. Knowledge of domain vocabulary supports the comprehension of a specific domain for later code maintenance or evolution. We present experiments conducted in two selected domains: application servers and we...

  19. Variable selection for confounder control, flexible modeling and Collaborative Targeted Minimum Loss-based Estimation in causal inference

    Science.gov (United States)

    Schnitzer, Mireille E.; Lok, Judith J.; Gruber, Susan

    2015-01-01

    This paper investigates the appropriateness of the integration of flexible propensity score modeling (nonparametric or machine learning approaches) in semiparametric models for the estimation of a causal quantity, such as the mean outcome under treatment. We begin with an overview of some of the issues involved in knowledge-based and statistical variable selection in causal inference and the potential pitfalls of automated selection based on the fit of the propensity score. Using a simple example, we directly show the consequences of adjusting for pure causes of the exposure when using inverse probability of treatment weighting (IPTW). Such variables are likely to be selected when using a naive approach to model selection for the propensity score. We describe how the method of Collaborative Targeted minimum loss-based estimation (C-TMLE; van der Laan and Gruber, 2010) capitalizes on the collaborative double robustness property of semiparametric efficient estimators to select covariates for the propensity score based on the error in the conditional outcome model. Finally, we compare several approaches to automated variable selection in low-and high-dimensional settings through a simulation study. From this simulation study, we conclude that using IPTW with flexible prediction for the propensity score can result in inferior estimation, while Targeted minimum loss-based estimation and C-TMLE may benefit from flexible prediction and remain robust to the presence of variables that are highly correlated with treatment. However, in our study, standard influence function-based methods for the variance underestimated the standard errors, resulting in poor coverage under certain data-generating scenarios. PMID:26226129

  20. A novel peptide, selected from phage display library of random peptides, can efficiently target into human breast cancer cell

    Institute of Scientific and Technical Information of China (English)

    DONG Jian; LIU WeiQing; JIANG AiMei; ZHANG KeJian; CHEN MingQing

    2008-01-01

    To develop a targeting vector for breast cancer biotherapy, MDA-MB-231 cell, a human breast cancer cell line, was co-cultured with pC89 (9 aa) phage display library of random peptides. In multiple inde-pendent peptide-presenting phage screening trials, subtilisin was used as a protease to inactivate ex-tra-cellular phages. The internalized phages were collected by cell lysising and amplified in E. coli XLI-Blue. Through five rounds of selection, the peptide-presenting phages which could be internalized in MDA-MB-231 cells were isolated. A comparison was made between internalization capacities of pep-tide-presenting phages isolated from MDA-MB-231 cells and RGD-integrin binding phage by cocultur-ing them with other human tumor cell lines and normal cells. The nucleotide sequences of isolated peptide-presenting phages were then determined by DNA sequencing. To uncover whether phage coat protein or amino acid order was required for the character of the peptide to MDA-MB-231 cells, three peptides were synthesized. They are CASPSGALRSC, ASPSGALRS and CGVIFDHSVPC (the shifted sequence of CASPSGALRSC), and after coculturing them with different cell lines, their targeting ca-pacities to MDA-MB-231 cells were detected. These data suggested that the internalization process was highly selective, and capable of capturing a specific peptide from parent peptide variants. Moreover, the targeting internalization event of peptides was an amino acid sequence dependent manner. The results demonstrated the feasibility of using phage display library of random peptides to develop new targeting system for intracellular delivery of macromolecules, and the peptide we obtained might be modified as a targeting vector for breast cancer gene therapy.

  1. ANPS - AUTOMATIC NETWORK PROGRAMMING SYSTEM

    Science.gov (United States)

    Schroer, B. J.

    1994-01-01

    Development of some of the space program's large simulation projects -- like the project which involves simulating the countdown sequence prior to spacecraft liftoff -- requires the support of automated tools and techniques. The number of preconditions which must be met for a successful spacecraft launch and the complexity of their interrelationship account for the difficulty of creating an accurate model of the countdown sequence. Researchers developed ANPS for the Nasa Marshall Space Flight Center to assist programmers attempting to model the pre-launch countdown sequence. Incorporating the elements of automatic programming as its foundation, ANPS aids the user in defining the problem and then automatically writes the appropriate simulation program in GPSS/PC code. The program's interactive user dialogue interface creates an internal problem specification file from user responses which includes the time line for the countdown sequence, the attributes for the individual activities which are part of a launch, and the dependent relationships between the activities. The program's automatic simulation code generator receives the file as input and selects appropriate macros from the library of software modules to generate the simulation code in the target language GPSS/PC. The user can recall the problem specification file for modification to effect any desired changes in the source code. ANPS is designed to write simulations for problems concerning the pre-launch activities of space vehicles and the operation of ground support equipment and has potential for use in developing network reliability models for hardware systems and subsystems. ANPS was developed in 1988 for use on IBM PC or compatible machines. The program requires at least 640 KB memory and one 360 KB disk drive, PC DOS Version 2.0 or above, and GPSS/PC System Version 2.0 from Minuteman Software. The program is written in Turbo Prolog Version 2.0. GPSS/PC is a trademark of Minuteman Software. Turbo Prolog

  2. Tricyclic covalent inhibitors selectively target Jak3 through an active site thiol.

    Science.gov (United States)

    Goedken, Eric R; Argiriadi, Maria A; Banach, David L; Fiamengo, Bryan A; Foley, Sage E; Frank, Kristine E; George, Jonathan S; Harris, Christopher M; Hobson, Adrian D; Ihle, David C; Marcotte, Douglas; Merta, Philip J; Michalak, Mark E; Murdock, Sara E; Tomlinson, Medha J; Voss, Jeffrey W

    2015-02-20

    The action of Janus kinases (JAKs) is required for multiple cytokine signaling pathways, and as such, JAK inhibitors hold promise for treatment of autoimmune disorders, including rheumatoid arthritis, inflammatory bowel disease, and psoriasis. However, due to high similarity in the active sites of the four members (Jak1, Jak2, Jak3, and Tyk2), developing selective inhibitors within this family is challenging. We have designed and characterized substituted, tricyclic Jak3 inhibitors that selectively avoid inhibition of the other JAKs. This is accomplished through a covalent interaction between an inhibitor containing a terminal electrophile and an active site cysteine (Cys-909). We found that these ATP competitive compounds are irreversible inhibitors of Jak3 enzyme activity in vitro. They possess high selectivity against other kinases and can potently (IC50 < 100 nm) inhibit Jak3 activity in cell-based assays. These results suggest irreversible inhibitors of this class may be useful selective agents, both as tools to probe Jak3 biology and potentially as therapies for autoimmune diseases. PMID:25552479

  3. Selective targeting of nuclear receptor FXR by avermectin analogues with therapeutic effects on nonalcoholic fatty liver disease

    Science.gov (United States)

    Jin, Lihua; Wang, Rui; Zhu, Yanlin; Zheng, Weili; Han, Yaping; Guo, Fusheng; Ye, Frank Bin; Li, Yong

    2015-01-01

    Non-alcoholic fatty liver disease (NAFLD) has become a predictive factor of death from many diseases. Farnesoid X receptor (FXR) is an ideal target for NAFLD drug development due to its crucial roles in lipid metabolism. The aim of this work is to examine the molecular mechanisms and functional roles of FXR modulation by avermectin analogues in regulating metabolic syndromes like NAFLD. We found that among avermectin analogues studied, the analogues that can bind and activate FXR are effective in regulating metabolic parameters tested, including reducing hepatic lipid accumulation, lowering serum cholesterol and glucose levels, and improving insulin sensitivity, in a FXR dependent manner. Mechanistically, the avermectin analogues that interact with FXR exhibited features as partial agonists, with distinctive properties in modulating coregulator recruitment. Structural features critical for avermectin analogues to selectively bind to FXR were also revealed. This study indicated that in addition to antiparasitic activity, avermectin analogues are promising drug candidates to treat metabolism syndrome including NAFLD by directly targeting FXR. Additionally, the structural features that discriminate the selective binding of FXR by avermectin analogues may provide a unique safe approach to design drugs targeting FXR signaling. PMID:26620317

  4. Automatic readout micrometer

    International Nuclear Information System (INIS)

    A measuring system is disclosed for surveying and very accurately positioning objects with respect to a reference line. A principal use of this surveying system is for accurately aligning the electromagnets which direct a particle beam emitted from a particle accelerator. Prior art surveying systems require highly skilled surveyors. Prior art systems include, for example, optical surveying systems which are susceptible to operator reading errors, and celestial navigation-type surveying systems, with their inherent complexities. The present invention provides an automatic readout micrometer which can very accurately measure distances. The invention has a simplicity of operation which practically eliminates the possibilities of operator optical reading error, owning to the elimination of traditional optical alignments for making measurements. The invention has an extendable arm which carries a laser surveying target. The extendable arm can be continuously positioned over its entire length of travel by either a coarse or fine adjustment without having the fine adjustment outrun the coarse adjustment until a reference laser beam is centered on the target as indicated by a digital readout. The length of the micrometer can then be accurately and automatically read by a computer and compared with a standardized set of alignment measurements. Due to its construction, the micrometer eliminates any errors due to temperature changes when the system is operated within a standard operating temperature range

  5. Selective inhibition of regulatory T cells by targeting the PI3K-Akt pathway.

    Science.gov (United States)

    Abu-Eid, Rasha; Samara, Raed N; Ozbun, Laurent; Abdalla, Maher Y; Berzofsky, Jay A; Friedman, Kevin M; Mkrtichyan, Mikayel; Khleif, Samir N

    2014-11-01

    Despite the strides that immunotherapy has made in mediating tumor regression, the clinical effects are often transient, and therefore more durable responses are still needed. The temporary nature of the therapy-induced immune response can be attributed to tumor immune evasion mechanisms, mainly the effect of suppressive immune cells and, in particular, regulatory T cells (Treg). Although the depletion of Tregs has been shown to be effective in enhancing immune responses, selective depletion of these suppressive cells without affecting other immune cells has not been very successful, and new agents are sought. We found that PI3K-Akt pathway inhibitors selectively inhibit Tregs with minimal effect on conventional T cells (Tconv). Our results clearly show selective in vitro inhibition of activation (as represented by a decrease in downstream signaling) and proliferation of Tregs in comparison with Tconvs when treated with different Akt and PI3K inhibitors. This effect has been observed in both human and murine CD4 T cells. In vivo treatment with these inhibitors resulted in a significant and selective reduction in Tregs in both naïve and tumor-bearing mice. Furthermore, these PI3K-Akt inhibitors led to a significant therapeutic antitumor effect, which was shown to be Treg dependent. Here, we report the use of PI3K-Akt pathway inhibitors as potent agents for the selective depletion of suppressive Tregs. We show that these inhibitors are able to enhance the antitumor immune response and are therefore promising clinical reagents for Treg depletion. PMID:25080445

  6. Selective inhibition of regulatory T cells by targeting PI3K-Akt pathway

    Science.gov (United States)

    Abu-Eid, R; Samara, RN; Ozbun, L; Abdalla, MY; Berzofsky, JA; Friedman, KM; Mkrtichyan, M; Khleif, SN

    2014-01-01

    Despite the strides that immunotherapy has made in mediating tumor regression, the clinical effects are often transient, and therefore more durable responses still are needed. The temporary nature of the therapy-induced immune response can be attributed to tumor immune evasion mechanisms, mainly the effect of suppressive immune cells and, in particular, T regulatory cells (Treg). Although the depletion of Treg has been shown to be effective in enhancing immune responses, selective depletion of these suppressive cells without affecting other immune cells has not been very successful, and new agents are sought. We found that PI3K-Akt pathway inhibitors selectively inhibit Treg with minimal effect on conventional T cells (Tconv). Our results clearly show selective in vitro inhibition of activation (as represented by a decrease in downstream signaling) and proliferation of Treg in comparison to Tconv when treated with different Akt and PI3K inhibitors. This effect has been observed in both human and murine CD4 T cells. In vivo treatment with these inhibitors resulted in a significant and selective reduction in Treg both in naïve and tumor-bearing mice. Furthermore, these PI3K-Akt inhibitors led to a significant therapeutic antitumor effect, which was shown to be Treg-dependent. Here, we report the use of PI3K-Akt pathway inhibitors as potent agents for the selective depletion of suppressive Treg. We show that these inhibitors are able to enhance the antitumor immune response and are therefore promising clinical reagents for Treg-depletion. PMID:25080445

  7. A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases.

    Science.gov (United States)

    Carels, Nicolas; Tilli, Tatiana; Tuszynski, Jack A

    2015-01-01

    In this report, we describe a strategy for the optimized selection of protein targets suitable for drug development against neoplastic diseases taking the particular case of breast cancer as an example. We combined human interactome and transcriptome data from malignant and control cell lines because highly connected proteins that are up-regulated in malignant cell lines are expected to be suitable protein targets for chemotherapy with a lower rate of undesirable side effects. We normalized transcriptome data and applied a statistic treatment to objectively extract the sub-networks of down- and up-regulated genes whose proteins effectively interact. We chose the most connected ones that act as protein hubs, most being in the signaling network. We show that the protein targets effectively identified by the combination of protein connectivity and differential expression are known as suitable targets for the successful chemotherapy of breast cancer. Interestingly, we found additional proteins, not generally targeted by drug treatments, which might justify the extension of existing formulation by addition of inhibitors designed against these proteins with the consequence of improving therapeutic outcomes. The molecular alterations observed in breast cancer cell lines represent either driver events and/or driver pathways that are necessary for breast cancer development or progression. However, it is clear that signaling mechanisms of the luminal A, B and triple negative subtypes are different. Furthermore, the up- and down-regulated networks predicted subtype-specific drug targets and possible compensation circuits between up- and down-regulated genes. We believe these results may have significant clinical implications in the personalized treatment of cancer patients allowing an objective approach to the recycling of the arsenal of available drugs to the specific case of each breast cancer given their distinct qualitative and quantitative molecular traits. PMID:25625699

  8. A computational strategy to select optimized protein targets for drug development toward the control of cancer diseases.

    Directory of Open Access Journals (Sweden)

    Nicolas Carels

    Full Text Available In this report, we describe a strategy for the optimized selection of protein targets suitable for drug development against neoplastic diseases taking the particular case of breast cancer as an example. We combined human interactome and transcriptome data from malignant and control cell lines because highly connected proteins that are up-regulated in malignant cell lines are expected to be suitable protein targets for chemotherapy with a lower rate of undesirable side effects. We normalized transcriptome data and applied a statistic treatment to objectively extract the sub-networks of down- and up-regulated genes whose proteins effectively interact. We chose the most connected ones that act as protein hubs, most being in the signaling network. We show that the protein targets effectively identified by the combination of protein connectivity and differential expression are known as suitable targets for the successful chemotherapy of breast cancer. Interestingly, we found additional proteins, not generally targeted by drug treatments, which might justify the extension of existing formulation by addition of inhibitors designed against these proteins with the consequence of improving therapeutic outcomes. The molecular alterations observed in breast cancer cell lines represent either driver events and/or driver pathways that are necessary for breast cancer development or progression. However, it is clear that signaling mechanisms of the luminal A, B and triple negative subtypes are different. Furthermore, the up- and down-regulated networks predicted subtype-specific drug targets and possible compensation circuits between up- and down-regulated genes. We believe these results may have significant clinical implications in the personalized treatment of cancer patients allowing an objective approach to the recycling of the arsenal of available drugs to the specific case of each breast cancer given their distinct qualitative and quantitative molecular

  9. Target-selective homologous recombination cloning for high-throughput generation of monoclonal antibodies from single plasma cells

    Directory of Open Access Journals (Sweden)

    Isobe Masaharu

    2011-04-01

    Full Text Available Abstract Background Molecular cloning of functional immunoglobulin genes from single plasma cells is one of the most promising technologies for the rapid development of monoclonal antibody drugs. However, the proper insertion of PCR-amplified immunoglobulin genes into expression vectors remains an obstacle to the high-throughput production of recombinant monoclonal antibodies. Results We developed a single-step cloning method, target-selective homologous recombination (TS-HR, in which PCR-amplified immunoglobulin variable genes were selectively inserted into vectors, even in the presence of nonspecifically amplified DNA. TS-HR utilizes Red/ET-mediated homologous recombination with a target-selective vector (TS-vector with unique homology arms on its termini. Using TS-HR, immunoglobulin variable genes were cloned directly into expression vectors by co-transforming unpurified PCR products and the TS-vector into E. coli. Furthermore, the high cloning specificity of TS-HR allowed plasmids to be extracted from pools of transformed bacteria without screening single colonies for correct clones. We present a one-week protocol for the production of recombinant mouse monoclonal antibodies from large numbers of single plasma cells. Conclusion The time requirements and limitations of traditional cloning procedures for the production of recombinant immunoglobulins have been significantly reduced with the development of the TS-HR cloning technique.

  10. Design of hypoxia-targeting radiopharmaceuticals: selective uptake of copper-64 complexes in hypoxic cells in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Dearling, J.L.J.; Lewis, J.S.; Mullen, G.E.D.; Rae, M.T. [Biosciences Dept., University of Kent, Canterbury (United Kingdom); Zweit, J. [Joint Dept of Physics, Institute of Cancer Research, Sutton (United Kingdom); Blower, P.J. [Biosciences Dept., University of Kent, Canterbury (United Kingdom)]|[Nuclear Medicine Dept, Kent and Canterbury Hospital, Canterbury (United Kingdom)

    1998-07-01

    The well-known perfusion tracer CuPTSM, labelled with {sup 62}Cu or {sup 64}Cu, is believed to be trapped in cells non-selectively by a bioreductive mechanism. It is proposed that by modifying the ligand to increase its electron donor strength (for example by adding alkyl functionality or replacing sulphur ligands with oxygen ligands), the copper complexes will become less easily reduced and tracers with selectivity for hypoxic tissues could thus be developed. The aim of this work was to prepare {sup 64}Cu-labelled complexes of two series of ligands, based on the bis(thiosemicarbazone) (13 ligands) and bis(salicylaldimine) (3 ligands) skeletons, and to evaluate the hypoxia dependence of their uptake in cells. The complexes were incubated with Chinese hamster ovary cells under normoxic and hypoxic conditions, and the cells isolated by centrifugation to determine radioactivity uptake at various time points up to 90 min. Several members of both series demonstrated significant (P<0.05) or highly significant (P<0.01) hypoxia selectivity, indicating that both series of complexes offer a basis for development of hypoxia-targeting radiopharmaceuticals for positron emission tomography ({sup 60}Cu, {sup 61}Cu, {sup 62}Cu, {sup 64}Cu) and targeted radiotherapy ({sup 64}Cu, {sup 67}Cu). (orig.) With 5 figs., 1 tab., 10 refs.

  11. Role of receptor tyrosine kinases in gastric cancer: New targets for a selective therapy

    Institute of Scientific and Technical Information of China (English)

    JC Becker; C Müller-Tidow; H Serve; W Domschke; T Pohle

    2006-01-01

    Receptor tyrosine kinases (RTKs) such as the epidermal growth factor receptor family participate in several steps of tumor formation including proliferation and metastatic spread. Several known RTKs are upregulated in gastric cancer being prime targets of a tailored therapy. Only preliminary data exist, however, on the use of the currently clinically available drugs such as trastuzumab,cetuximab, bevacizumab, gefitinib, erlotinib, and imatinib in the setting of gastric cancer. Preclinical data suggest a potential benefit of their use, especially in combination with "conventional" cytostatic therapy. This review summarizes the current knowledge about their use in cancer therapy as well as new approaches and drugs to optimize treatment success.

  12. Selective inhibition of regulatory T cells by targeting PI3K-Akt pathway

    OpenAIRE

    Abu-Eid, R; Samara, RN; Ozbun, L; Abdalla, MY; Berzofsky, JA; Friedman, KM; Mkrtichyan, M; Khleif, SN

    2014-01-01

    Despite the strides that immunotherapy has made in mediating tumor regression, the clinical effects are often transient, and therefore more durable responses still are needed. The temporary nature of the therapy-induced immune response can be attributed to tumor immune evasion mechanisms, mainly the effect of suppressive immune cells and, in particular, T regulatory cells (Treg). Although the depletion of Treg has been shown to be effective in enhancing immune responses, selective depletion o...

  13. Targeted Quantitation of Acetylated Lysine Peptides by Selected Reaction Monitoring Mass Spectrometry

    OpenAIRE

    Rardin, Matthew J.; Held, Jason M.; Gibson, Bradford W.

    2013-01-01

    Mass spectrometry (MS) allows for the large-scale identification of multiple peptide analytes in complex mixtures. However, the low abundance of acetylated peptides in the overall mixture requires an enrichment step. After enrichment, the resulting acetylated peptides of interest can be quantitated using selected reaction monitoring (SRM)-MS with stable isotope dilution. Here, we describe the enrichment of lysine acetylated peptides from typsin digested mouse liver mitochondria, and the targe...

  14. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells

    Science.gov (United States)

    Geninatti Crich, S.; Cadenazzi, M.; Lanzardo, S.; Conti, L.; Ruiu, R.; Alberti, D.; Cavallo, F.; Cutrin, J. C.; Aime, S.

    2015-04-01

    In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation.In this work the selective uptake of native horse spleen ferritin and apoferritin loaded with MRI contrast agents has been assessed in human breast cancer cells (MCF-7 and MDA-MB-231). The higher expression of L-ferritin receptors (SCARA5) led to an enhanced uptake in MCF-7 as shown in T2 and T1 weighted MR images, respectively. The high efficiency of ferritin internalization in MCF-7 has been exploited for the simultaneous delivery of curcumin, a natural therapeutic molecule endowed with antineoplastic and anti-inflammatory action, and the MRI contrast agent Gd-HPDO3A. This theranostic system is able to treat selectively breast cancer cells over-expressing ferritin receptors. By entrapping in apoferritin both Gd-HPDO3A and curcumin, it was possible to deliver a therapeutic dose of 167 μg ml-1 (as calculated by MRI) of this natural drug to MCF-7 cells, thus obtaining a significant reduction of cell proliferation. Electronic supplementary information (ESI) available: Competition studies with free apoferritin, Fig. S1; APO-FITC intracellular distribution by

  15. Patients with schizophrenia do not preserve automatic grouping when mentally re-grouping figures: shedding light on an ignored difficulty

    Directory of Open Access Journals (Sweden)

    AnneGiersch

    2012-08-01

    Full Text Available Looking at a pair of objects is easy when automatic grouping mechanisms bind these objects together, but visual exploration can also be more flexible. It is possible to mentally ‘re-group’ two objects that are not only separate but belong to different pairs of objects. ‘Re-grouping’ is in conflict with automatic grouping, since it entails a separation of each item from the set it belongs to. This ability appears to be impaired in patients with schizophrenia. Here we check if this impairment is selective, which would suggest a dissociation between grouping and ‘re-grouping’, or if it impacts on usual, automatic grouping, which would call for a better understanding of the interactions between automatic grouping and ‘re-grouping’. Sixteen outpatients with schizophrenia and healthy controls had to identify two identical and contiguous target figures within a display of circles and squares alternating around a fixation point. Eye-tracking was used to check central fixation. The target pair could be located in the same or separate hemifields. Identical figures were grouped by a connector (grouped automatically or not (to be re-grouped. Attention modulation of automatic grouping was tested by manipulating the proportion of connected and unconnected targets, thus prompting subjects to focalize on either connected or unconnected pairs. Both groups were sensitive to automatic grouping in most conditions, but patients were unusually slowed down for connected targets while focalizing on unconnected pairs. In addition, this unusual effect occurred only when target were presented within the same hemifield. Patients and controls differed on this asymmetry between within- and across-hemifield presentation, suggesting that patients with schizophrenia do not re-group figures in the same way as controls do. We discuss possible implications on how ‘re-grouping’ ties in with ongoing, automatic perception in healthy volunteers.

  16. Predicting the Interactome of Xanthomonas oryzae pathovar oryzae for target selection and DB service

    Directory of Open Access Journals (Sweden)

    Yoon Kyong-Oh

    2008-01-01

    Full Text Available Abstract Background Protein-protein interactions (PPIs play key roles in various cellular functions. In addition, some critical inter-species interactions such as host-pathogen interactions and pathogenicity occur through PPIs. Phytopathogenic bacteria infect hosts through attachment to host tissue, enzyme secretion, exopolysaccharides production, toxins release, iron acquisition, and effector proteins secretion. Many such mechanisms involve some kind of protein-protein interaction in hosts. Our first aim was to predict the whole protein interaction pairs (interactome of Xanthomonas oryzae pathovar oryzae (Xoo that is an important pathogenic bacterium that causes bacterial blight (BB in rice. We developed a detection protocol to find possibly interacting proteins in its host using whole genome PPI prediction algorithms. The second aim was to build a DB server and a bioinformatic procedure for finding target proteins in Xoo for developing pesticides that block host-pathogen protein interactions within critical biochemical pathways. Description A PPI network in Xoo proteome was predicted by bioinformatics algorithms: PSIMAP, PEIMAP, and iPfam. We present the resultant species specific interaction network and host-pathogen interaction, XooNET. It is a comprehensive predicted initial PPI data for Xoo. XooNET can be used by experimentalists to pick up protein targets for blocking pathological interactions. XooNET uses most of the major types of PPI algorithms. They are: 1 Protein Structural Interactome MAP (PSIMAP, a method using structural domain of SCOP, 2 Protein Experimental Interactome MAP (PEIMAP, a common method using public resources of experimental protein interaction information such as HPRD, BIND, DIP, MINT, IntAct, and BioGrid, and 3 Domain-domain interactions, a method using Pfam domains such as iPfam. Additionally, XooNET provides information on network properties of the Xoo interactome. Conclusion XooNET is an open and free public

  17. Lysosomotropism of basic cathepsin K inhibitors contributes to increased cellular potencies against off-target cathepsins and reduced functional selectivity.

    Science.gov (United States)

    Falgueyret, Jean-Pierre; Desmarais, Sylvie; Oballa, Renata; Black, W Cameron; Cromlish, Wanda; Khougaz, Karine; Lamontagne, Sonia; Massé, Frederic; Riendeau, Denis; Toulmond, Sylvie; Percival, M David

    2005-12-01

    The lysosomal cysteine protease cathepsin K is a target for osteoporosis therapy. The aryl-piperazine-containing cathepsin K inhibitor CRA-013783/L-006235 (1) displays greater than 4000-fold selectivity against the lysosomal/endosomal antitargets cathepsin B, L, and S. However, 1 and other aryl-piperazine-containing analogues, including balicatib (10), are approximately 10-100-fold more potent in cell-based enzyme occupancy assays than against each purified enzyme. This phenomenon arises from their basic, lipophilic nature, which results in lysosomal trapping. Consistent with its lysosomotropic nature, 1 accumulates in cells and in rat tissues of high lysosome content. In contrast, nonbasic aryl-morpholino-containing analogues do not exhibit lysosomotropic properties. Increased off-target activities of basic cathepsin K inhibitors were observed in a cell-based cathepsin S antigen presentation assay. No potency increases of basic inhibitors in a functional cathepsin K bone resorption whole cell assay were detected. Therefore, basic cathepsin K inhibitors, such as 1, suffer from reduced functional selectivities compared to those predicted using purified enzyme assays. PMID:16302795

  18. Design of RC frames for pre-selected collapse mechanism and target displacement using energy–balance

    Indian Academy of Sciences (India)

    Onur Merter; Taner Ucar

    2014-06-01

    In earthquake-prone countries, structures may be exposed to several seismic loads in any stage of building’s life. It is expected that the structures designed by engineers will show ductile behaviour under the effect of vertical and lateral loads and remain stable without making a sudden collapse. In consequence of nonlinear behaviour, plastic hinges are expected to form in structural members which are under the effect of external loads. Earthquake input energy is dissipated in plastic hinges, so, structures behave ductile. In this study, total energy of RC frames is calculated and the energy–based base shear force is determined by equating the total internal energy to the work done by external lateral design forces for pre-selected target displacement and collapse mechanism. Sections of RC frames are controlled if they can resist the calculated design lateral loads or not. If the capacity of the sections cannot withstand the external design loads, the design is rearranged and new sections are chosen. Beam and column sections that can resist the design loads securely are accepted as final sections of the energy–based design methodology. Pre-selected target displacement for desired performance level is checked using the results of nonlinear analyses. The results of the presented design methodology in this study are compatible with the results of nonlinear analyses.

  19. Host selection in the forest interior: cowbirds target ground-nesting species

    Science.gov (United States)

    Hahn, D.C.; Hatfield, J.S.

    2000-01-01

    We investigated patterns of cowbird host selection in a large (1300 ha), unfragmented forest in eastern New York in 1992-3 to determine whether cowbird parasitism rates can be attributed to species-specific traits or to other features associated with nest sites. Nest height was significantly associated with parasitism (P = 0.003) in this community of 23 species (n = 430 nests, 23% parasitized). Further analysis revealed that the difference in mean nest heights between parasitized and unparasitized nests was due to species identity, and within each species there was no difference in mean nest heights between parasitized and unparasitized nests. These results imply that during 1992-3 cowbirds in this forest specialized on species that have low nests and did not necessarily select low nests regardless of species. This was further supported by a negative association across all 23 species between mean nest height and parasitism rate (P = 0.03). Thus, although most of the forest-nesting species in this community experienced cowbird parasitism, there was a tendency for higher parasitism rates on low-nesting species such as the Ovenbird, Black-and-white Warbler, Louisiana Waterthrush, Veery, and Hermit Thrush. The Wood Thrush, a mid-range nester which is heavily parasitized in southern Illinois, experienced only 10% parasitism in our site and ranked 9th in parasitism rate, although it was the most abundant species in this forest in terms of the number of nests found. A long-term study is necessary to determine whether this cowbird population consistently parasitizes the ground-nesting species of this forest community more often than those nesting at higher levels or whether they periodically shift among hosts at different heights and in different habitats across the local landscape.

  20. Affinity peptide developed by phage display selection for targeting gastric cancer

    Institute of Scientific and Technical Information of China (English)

    Wen-Jie Zhang; Yan-Xia Sui; Arun Budha; Jian-Bao Zheng; Xue-Jun Sun; Ying-Chun Hou; Thomas D Wang; Shao-Ying Lu

    2012-01-01

    AIM:To develop an affinity peptide that binds to gastric cancer used for the detection of early gastric cancer.METHODS:A peptide screen was performed by biopanning the PhD-12 phage display library,clearing non-specific binders against tumor-adjacent normal appearing gastric mucosa and obtaining selective binding against freshly harvested gastric cancer tissues.Tumortargeted binding of selected peptides was confirmed by bound phage counts,enzyme-linked immunosorbent assay,competitive inhibition,fluorescence microscopy and semi-quantitative analysis on immunohistochemistry using different types of cancer tissues.RESULTS:Approximately 92.8% of the non-specific phage clones were subtracted from the original phage library after two rounds of biopanning against normalappearing gastric mucosa.After the third round of positive screening,the peptide sequence AADNAKTKSFPV (AAD) appeared in 25% (12/48) of the analyzed phages.For the control peptide,these values were 6.8 ± 2.3,5.1 ± 1.7,3.5 ± 2.1,4.6 ± 1.9 and 1.1 ± 0.5,respectively.The values for AAD peptide were statistically significant (P < 0.01) for gastric cancer as compared with other histological classifications and control peptide.CONCLUSION:A novel peptide is discovered to have a specific binding activity to gastric cancer,and can be used to distinguish neoplastic from normal gastric mucosa,demonstrating the potential for early cancer detection on endoscopy.

  1. Selective NFAT targeting in T cells ameliorates GvHD while maintaining antitumor activity.

    Science.gov (United States)

    Vaeth, Martin; Bäuerlein, Carina A; Pusch, Tobias; Findeis, Janina; Chopra, Martin; Mottok, Anja; Rosenwald, Andreas; Beilhack, Andreas; Berberich-Siebelt, Friederike

    2015-01-27

    Graft-versus-host disease (GvHD) is a life-threatening immunological complication after allogenic hematopoietic stem cell transplantation (allo-HCT). The intrinsic graft-versus-leukemia (GvL) effect, however, is the desirable curative benefit. Patients with acute GvHD are treated with cyclosporine A (CsA) or tacrolimus (FK506), which not only often causes severe adverse effects, but also interferes with the anticipated GvL. Both drugs inhibit calcineurin, thus at first suppressing activation of the nuclear factor of activated T cells (NFAT). Therefore, we explored the specific contribution of individual NFAT factors in donor T cells in animal models of GvHD and GvL. Ablation of NFAT1, NFAT2, or a combination of both resulted in ameliorated GvHD, due to reduced proliferation, target tissue homing, and impaired effector function of allogenic donor T cells. In contrast, the frequency of Foxp3(+) regulatory T (Treg) cells was increased and NFAT-deficient Tregs were fully protective in GvHD. CD8(+) T-cell recall response and, importantly, the beneficial antitumor activity were largely preserved in NFAT-deficient effector T cells. Thus, specific inhibition of NFAT opens an avenue for an advanced therapy of GvHD maintaining protective GvL. PMID:25583478

  2. Microinterventions targeting regulatory focus and regulatory fit selectively reduce dysphoric and anxious mood.

    Science.gov (United States)

    Strauman, Timothy J; Socolar, Yvonne; Kwapil, Lori; Cornwell, James F M; Franks, Becca; Sehnert, Steen; Higgins, E Tory

    2015-09-01

    Depression and generalized anxiety, separately and as comorbid states, continue to represent a significant public health challenge. Current cognitive-behavioral treatments are clearly beneficial but there remains a need for continued development of complementary interventions. This manuscript presents two proof-of-concept studies, in analog samples, of "microinterventions" derived from regulatory focus and regulatory fit theories and targeting dysphoric and anxious symptoms. In Study 1, participants with varying levels of dysphoric and/or anxious mood were exposed to a brief intervention either to increase or to reduce engagement in personal goal pursuit, under the hypothesis that dysphoria indicates under-engagement of the promotion system whereas anxiety indicates over-engagement of the prevention system. In Study 2, participants with varying levels of dysphoric and/or anxious mood received brief training in counterfactual thinking, under the hypothesis that inducing individuals in a state of promotion failure to generate subtractive counterfactuals for past failures (a non-fit) will lessen their dejection/depression-related symptoms, whereas inducing individuals in a state of prevention failure to generate additive counterfactuals for past failures (a non-fit) will lessen their agitation/anxiety-related symptoms. In both studies, we observed discriminant patterns of reduction in distress consistent with the hypothesized links between dysfunctional states of the two motivational systems and dysphoric versus anxious symptoms. PMID:26163353

  3. Fungal sterol C22-desaturase is not an antimycotic target as shown by selective inhibitors and testing on clinical isolates.

    Science.gov (United States)

    Müller, Christoph; Binder, Ulrike; Maurer, Elisabeth; Grimm, Christian; Giera, Martin; Bracher, Franz

    2015-09-01

    Inhibition of concise enzymes in ergosterol biosynthesis is one of the most prominent strategies for antifungal chemotherapy. Nevertheless, the enzymes sterol C5-desaturase and sterol C22-desaturase, which introduce double bonds into the sterol core and side chain, have not been fully investigated yet for their potential as antifungal drug targets. Lathosterol side chain amides bearing N-alkyl groups of proper length are known as potent inhibitors of the enzymes sterol C5-desaturase and sterol Δ(24)-reductase in mammalian cholesterol biosynthesis. Here we present the results of our evaluation of these amides for their ability to inhibit enzymes in fungal ergosterol biosynthesis. In the presence of inhibitor(s) an accumulation of sterols lacking a double bond at C22/23 (mainly ergosta-5,7-dien-3β-ol) was observed in Candida glabrata, Saccharomyces cerevisiae, and Yarrowia lipolytica. Hence, the lathosterol side chain amides were identified as selective inhibitors of the fungal sterol C22-desaturase, which was discussed as a specific target for novel antifungals. One representative inhibitor, (3S,20S)-20-N-butylcarbamoylpregn-7-en-3β-ol was subjected to antifungal susceptibility testing on patient isolates according to modified EUCAST guidelines. But, the test organisms showed no significant reduction of cell growth and/or viability up to an inhibitor concentration of 100μg/mL. This leads to the conclusion that sterol C22-desaturase is not an attractive target for the development of antifungals. PMID:26022150

  4. Tumor cell-selective apoptosis induction through targeting of KV10.1 via bifunctional TRAIL antibody

    Directory of Open Access Journals (Sweden)

    Pardo Luis A

    2011-09-01

    Full Text Available Abstract Background The search for strategies to target ion channels for therapeutic applications has become of increasing interest. Especially, the potassium channel KV10.1 (Ether-á-go-go is attractive as target since this surface protein is virtually not detected in normal tissue outside the central nervous system, but is expressed in approximately 70% of tumors from different origins. Methods We designed a single-chain antibody against an extracellular region of KV10.1 (scFv62 and fused it to the human soluble TRAIL. The KV10.1-specific scFv62 antibody -TRAIL fusion protein was expressed in CHO-K1 cells, purified by chromatography and tested for biological activity. Results Prostate cancer cells, either positive or negative for KV10.1 were treated with the purified construct. After sensitization with cytotoxic drugs, scFv62-TRAIL induced apoptosis only in KV10.1-positive cancer cells, but not in non-tumor cells, nor in tumor cells lacking KV10.1 expression. In co-cultures with KV10.1-positive cancer cells the fusion protein also induced apoptosis in bystander KV10.1-negative cancer cells, while normal prostate epithelial cells were not affected when present as bystander. Conclusions KV10.1 represents a novel therapeutic target for cancer. We could design a strategy that selectively kills tumor cells based on a KV10.1-specific antibody.

  5. Metabolic targeting of oncogene MYC by selective activation of the proton-coupled monocarboxylate family of transporters.

    Science.gov (United States)

    Gan, L; Xiu, R; Ren, P; Yue, M; Su, H; Guo, G; Xiao, D; Yu, J; Jiang, H; Liu, H; Hu, G; Qing, G

    2016-06-01

    Deregulation of the MYC oncogene produces Myc protein that regulates multiple aspects of cancer cell metabolism, contributing to the acquisition of building blocks essential for cancer cell growth and proliferation. Therefore, disabling Myc function represents an attractive therapeutic option for cancer treatment. However, pharmacological strategies capable of directly targeting Myc remain elusive. Here, we identified that 3-bromopyruvate (3-BrPA), a drug candidate that primarily inhibits glycolysis, preferentially induced massive cell death in human cancer cells overexpressing the MYC oncogene, in vitro and in vivo, without appreciable effects on those exhibiting low MYC levels. Importantly, pharmacological inhibition of glutamine metabolism synergistically potentiated the synthetic lethal targeting of MYC by 3-BrPA due in part to the metabolic disturbance caused by this combination. Mechanistically, we identified that the proton-coupled monocarboxylate transporter 1 (MCT1) and MCT2, which enable efficient 3-BrPA uptake by cancer cells, were selectively activated by Myc. Two regulatory mechanisms were involved: first, Myc directly activated MCT1 and MCT2 transcription by binding to specific recognition sites of both genes; second, Myc transcriptionally repressed miR29a and miR29c, resulting in enhanced expression of their target protein MCT1. Of note, expressions of MCT1 and MCT2 were each significantly elevated in MYCN-amplified neuroblastomas and C-MYC-overexpressing lymphomas than in tumors without MYC overexpression, correlating with poor prognosis and unfavorable patient survival. These results identify a novel mechanism by which Myc sensitizes cells to metabolic inhibitors and validate 3-BrPA as potential Myc-selective cancer therapeutics. PMID:26434591

  6. Restricted Bipartite Graphs Based Target Detection for Hyperspectral Image Classification with GFA-LFDA Multi Feature Selection

    Directory of Open Access Journals (Sweden)

    T. Karthikeyan

    2015-06-01

    Full Text Available Hyper spectral imaging has recently become one of the most active research areas in remote sensing. Hyper spectral imagery possesses more spectral information than multispectral imagery because the number of spectral bands in hyper spectral imagery is in the hundreds rather than in the tens. However, the high dimensions of hyper spectral images cause redundancy in spatial-spectral feature domain and consider only spectral and spatial features only and ability of the classifier to excel even as training HSI images are limited. However, unless develop suitable algorithms for target detection or classification of the hyper spectral images data becomes difficult. Therefore, it is becomes essential to consider different features and find exact target detection rate to improve classification rate. In order to overcome this problem in this study presents a novel classification framework for hyper spectral data. Proposed system uses a graph based representation, Restricted Bipartite Graphs (RBG for exact detection of the class values. Before that the feature of the HSI images are selected using the Gaussian Firefly Algorithm (GFA for multiple feature selection and Local-Fisher’s Discriminant Analysis (LFDA based feature projection are performed in a raw spectral-spatial feature space for effective dimensionality reduction. Then RBG is proposed to represent the reduced feature results into graphical manner to solve exact target class matching problem, in hyper spectral imaginary. Classification is performed using the Hybrid Genetic Fuzzy Neural Network (HGFNN, Genetic algorithm is used to optimize the weights of the fuzzifier and the defuzzifier for labeled and unlabeled data samples. Experimentation results show that the proposed GFA-LFDA-RBG-HGFNN method outperforms in terms of the classification accuracy and less misclassification results than traditional methods.

  7. 基于回光强度的平面标靶自动识别方法%Automatic recognition method of planar target based on return light intensity

    Institute of Scientific and Technical Information of China (English)

    王力; 李广云; 张洪新

    2011-01-01

    平面标靶在中长距离三维激光扫描仪的检校、数据采集、单点测量等环节中发挥着重要作用,而平面标靶的高精度、自动化识别是在其使用中面临的一个关键问题.在分析扫描数据特点的基础上,提出一种基于回光强度的平面标靶自动识别方法.具体的步骤为:改正回光强度以消除距离的影响;基于回光强度进行阈值分割以得到平面标靶点云;提出一种基于扫描线的聚类算法,将平面标靶点云聚集在一起;采用形状检测技术排除非标靶对象;采用回光强度加权法计算平面标靶中心的三维坐标.通过对Riegl公司的三维激光扫描仪LMS Z620获取的实测数据进行实验,结果表明:此方法能完成标靶的快速、全自动识别,点位精度优于2mm,能够满足测量任务的需要.%Planar target plays an important role in the calibration, data collection and single point measurement of 3D laser scanner of middle and long range. The high precision and automatic recognition of planar targets is a key problem in application of laser scanner. A new recognizing method was put forward by using return light intensity based on analyzing the character of scan data. The steps are as follows: the return light intensity was corrected to eliminate the effects of distance. The point cloud of planar target was obtained by threshold segmenting based on return light intensity. A cluster method was proposed to gather the point cloud of planar target. The area detection was adopted to eliminate those objects which were not real target. 3D coordinate of planar target center was computed by adopting return light intensity weighting method. Experimental results obtained by using Riegl's LMS Z620 show that this method can realize the full automatic recognition quickly with the accuracy of point position better than 2 mm and meet the needs of survey task.

  8. Targeted selective treatment for worm management--how do we sell rational programs to farmers?

    Science.gov (United States)

    van Wyk, J A; Hoste, H; Kaplan, R M; Besier, R B

    2006-07-31

    Seriously escalating global anthelmintic resistance in gastrointestinal nematodes of small ruminants has spawned a variety of alternatives to anthelmintics for worm management, based on the need for sustainable Integrated Parasite Management (sIPM). Pivotal to the sIPM approach is the concept of refugia, the proportion of a given parasite population that escapes exposure to control measures. By balancing drug applications with the maintenance of refugia, the accumulation of anthelmintic resistance alleles in worm populations can be considerably delayed, while still providing good levels of control. The over-dispersed nature of parasitic infections provides an opportunity to achieve this balance, by targeting treatments to the members of a flock or herd that are least tolerant to nematode infection. However, implementation of this strategy has only recently become feasible, with the development of the FAMACHA((c)) system for clinical evaluation of anaemia due to haemonchosis. Subsequently, the use of milk yields has proven an effective indicator in dairy goats infected predominantly with nematodes other than Haemonchus contortus. In addition, short-term weight changes and perhaps also body condition scoring may provide indices of parasitism, permitting the rapid identification of animals likely to benefit from treatment. However, sIPM and refugia-based approaches are more complex than whole-flock treatments in conventional programs, and adoption by farmers is most likely where the theoretical basis is understood. As close communication with informed advisors is generally limited, there is a danger that sIPM will remain a theoretical concept without alternative modes of communication. The development of computer-based decision support programs, which use epidemiological, seasonal and clinical information to provide recommendations for specific situations, should be accorded high priority in the future development of worm management systems. PMID:16774807

  9. Identification of compounds that selectively target highly chemotherapy refractory neuroblastoma cancer stem cells.

    Science.gov (United States)

    Díaz-Carballo, David; Acikelli, Ali Haydar; Bardenheuer, Walter; Gustmann, Sebastian; Malak, Sascha; Stoll, Raphael; Kedziorski, Thorsten; Nazif, Mhd Ali; Jastrow, Holger; Wennemuth, Gunter; Dammann, Philip; Feigel, Martin; Strumberg, Dirk

    2014-09-01

    Relapse of cancer months or years after an apparently successful therapy is probably caused by cancer stem cells (CSCs) due to their intrinsic features like dormant periods, radiorefraction, and acquired multidrug resistance (MDR) phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack of currently efficacious interventions remains a major problem in the treatment of malignancies, together with the inability of existing drugs to destroy specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory extracranial tumors in infants with very low survival rates. So far, no effective cytostatics against this kind of tumors are clinically available. Therefore, we have put much effort into the development of agents to efficiently combat this malignancy. For this purpose, we tested several compounds isolated from Cuban propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which expressed several characteristics of tumor-initiating cells both in in-vitro and in-vivo models. Some small molecules such as flavonoids and polycyclic polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC cycles and identified employing mass spectrometry and NMR spectroscopic techniques. Their cytotoxicity was first screened in sensitive cell systems by MTT proliferation assays and afterwards studied in less sensitive neuroblastoma iCSC models. We found several compounds with considerable anti-iCSC activity, most of them belonging to the PPAP class. The majority of the compounds act in a pleiotropic manner on the molecular biology of tumors although their specific targets remain unclear. Nevertheless, two substances, one of them a flavonoid, induced a strong disruption of tubulin polymerization. In addition, an unknown compound strongly inhibited replicative enzymes like toposimerases I/II and DNA polymerase. Here, we report for the first time cytotoxic activities of small molecules isolated from Caribbean propolis

  10. Targeted reengineering of protein geranylgeranyltransferase type I selectivity functionally implicates active-site residues in protein-substrate recognition.

    Science.gov (United States)

    Gangopadhyay, Soumyashree A; Losito, Erica L; Hougland, James L

    2014-01-21

    Posttranslational modifications are vital for the function of many proteins. Prenylation is one such modification, wherein protein geranylgeranyltransferase type I (GGTase-I) or protein farnesyltransferase (FTase) modify proteins by attaching a 20- or 15-carbon isoprenoid group, respectively, to a cysteine residue near the C-terminus of a target protein. These enzymes require a C-terminal Ca1a2X sequence on their substrates, with the a1, a2, and X residues serving as substrate-recognition elements for FTase and/or GGTase-I. While crystallographic structures of rat GGTase-I show a tightly packed and hydrophobic a2 residue binding pocket, consistent with a preference for moderately sized a2 residues in GGTase-I substrates, the functional impact of enzyme-substrate contacts within this active site remains to be determined. Using site-directed mutagenesis and peptide substrate structure-activity studies, we have identified specific active-site residues within rat GGTase-I involved in substrate recognition and developed novel GGTase-I variants with expanded/altered substrate selectivity. The ability to drastically alter GGTase-I selectivity mirrors similar behavior observed in FTase but employs mutation of a distinct set of structurally homologous active-site residues. Our work demonstrates that tunable selectivity may be a general phenomenon among multispecific enzymes involved in posttranslational modification and raises the possibility of variable substrate selectivity among GGTase-I orthologues from different organisms. Furthermore, the GGTase-I variants developed herein can serve as tools for studying GGTase-I substrate selectivity and the effects of prenylation pathway modifications on specific proteins. PMID:24344934

  11. Target-Driven Positive Selection at Hot Spots of Scorpion Toxins Uncovers Their Potential in Design of Insecticides.

    Science.gov (United States)

    Zhu, Limei; Peigneur, Steve; Gao, Bin; Zhang, Shangfei; Tytgat, Jan; Zhu, Shunyi

    2016-08-01

    Positive selection sites (PSSs), a class of amino acid sites with an excess of nonsynonymous to synonymous substitutions, are indicators of adaptive molecular evolution and have been detected in many protein families involved in a diversity of biological processes by statistical approaches. However, few studies are conducted to evaluate their functional significance and the driving force behind the evolution (i.e., agent of selection). Scorpion α-toxins are a class of multigene family of peptide neurotoxins affecting voltage-gated Na(+ )(Nav) channels, whose members exhibit differential potency and preference for insect and mammalian Nav channels. In this study, we undertook a systematical molecular dissection of nearly all the PSSs newly characterized in the Mesobuthus α-toxin family and a two-residue insertion ((19)AlaPhe(20)) located within a positively selected loop via mutational analysis of α-like MeuNaTxα-5, one member affecting both insect and mammalian Nav channels. This allows to identify hot-spot residues on its functional face involved in interaction with the receptor site of Nav channels, which comprises two PSSs (Ile(40) and Leu(41)) and the small insertion, both located on two spatially separated functional loops. Mutations at these hot-spots resulted in a remarkably decreased anti-mammalian activity in MeuNaTxα-5 with partially impaired or enhanced insecticide activity, suggesting the potential of PSSs in designing promising candidate insecticides from scorpion α-like toxins. Based on an experiment-guided toxin-channel complex model and high evolutionary variability in the receptor site of predators and prey of scorpions, we provide new evidence for target-driven adaptive evolution of scorpion toxins to deal with their targets' diversity. PMID:27189560

  12. Nature's inordinate fondness for metabolic enzymes: why metabolic enzyme loci are so frequently targets of selection.

    Science.gov (United States)

    Marden, James H

    2013-12-01

    Metabolic enzyme loci were some of the first genes accessible for molecular evolution and ecology research. New technologies now make the whole genome, transcriptome or proteome readily accessible, allowing unbiased scans for loci exhibiting significant differences in allele frequency or expression level and associated with phenotypes and/or responses to natural selection. With surprising frequency and in many cases in proportions greater than chance relative to other genes, glycolysis and TCA cycle enzyme loci appear among the genes with significant associations in these studies. Hence, there is an ongoing need to understand the basis for fitness effects of metabolic enzyme polymorphisms. Allele-specific effects on the binding affinity and catalytic rate of individual enzymes are well known, but often of uncertain significance because metabolic control theory and in vivo studies indicate that many individual metabolic enzymes do not affect pathway flux rate. I review research, so far little used in evolutionary biology, showing that metabolic enzyme substrates affect signalling pathways that regulate cell and organismal biology, and that these enzymes have moonlighting functions. To date there is little knowledge of how alleles in natural populations affect these phenotypes. I discuss an example in which alleles of a TCA enzyme locus associate with differences in a signalling pathway and development, organismal performance, and ecological dynamics. Ultimately, understanding how metabolic enzyme polymorphisms map to phenotypes and fitness remains a compelling and ongoing need for gaining robust knowledge of ecological and evolutionary processes. PMID:24106889

  13. Targeted selected reaction monitoring mass spectrometric immunoassay for insulin-like growth factor 1.

    Directory of Open Access Journals (Sweden)

    Eric E Niederkofler

    Full Text Available Insulin-like growth factor 1 (IGF1 is an important biomarker of human growth disorders that is routinely analyzed in clinical laboratories. Mass spectrometry-based workflows offer a viable alternative to standard IGF1 immunoassays, which utilize various pre-analytical preparation strategies. In this work we developed an assay that incorporates a novel sample preparation method for dissociating IGF1 from its binding proteins. The workflow also includes an immunoaffinity step using antibody-derivatized pipette tips, followed by elution, trypsin digestion, and LC-MS/MS separation and detection of the signature peptides in a selected reaction monitoring (SRM mode. The resulting quantitative mass spectrometric immunoassay (MSIA exhibited good linearity in the range of 1 to 1,500 ng/mL IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest limits of detection of 1 ng/mL. The linearity and recovery characteristics of the assay were also established, and the new method compared to a commercially available immunoassay using a large cohort of human serum samples. The IGF1 SRM MSIA is well suited for use in clinical laboratories.

  14. Nanocrystalline diamond sensor targeted for selective CRP detection: an ATR-FTIR spectroscopy study.

    Science.gov (United States)

    Andersson, Per Ola; Viberg, Pernilla; Forsberg, Pontus; Nikolajeff, Fredrik; Österlund, Lars; Karlsson, Mikael

    2016-05-01

    Protein immobilization on functionalized fluorine-terminated nanocrystalline (NCD) films was studied by attenuated total reflection Fourier transform infrared (ATR-FTIR) spectroscopy using an immobilization protocol developed to specifically bind C-reactive protein (CRP). Using an ATR-FTIR spectroscopy method employing a force-controlled anvil-type configuration, three critical steps of the ex situ CRP immobilization were analyzed. First, the NCD surface was passivated by deposition of a copolymer layer consisting of polyethylene oxide and polypropylene oxide. Second, a synthetic modified polypeptide binder with high affinity to CRP was covalently attached to the polymeric film. Third, CRP dissolved in aqueous buffer in concentrations of 10-20 μg/mL was added on the functionalized NCD surface. Both the amide I and II bands, due to the polypeptide binder and CRP, were clearly observed in ATR-FTIR spectra. CRP amide I bands were extracted from difference spectra and yielded bands that agreed well with the reported amide I band of free (non-bonded) CRP in solution. Thus, our results show that CRP retains its secondary structure when it is attached to the polypeptide binders. Compared to previous IR studies of CRP in solution, about 200 times lower concentration was applied in the present study. Graphical Abstract Direct non-destructive ATR-FTIR analysis of C-reactive protein (CRP) selectively bound to functionalized nanocrystalline diamond (NCD) sensor surface. PMID:27007740

  15. Targeting of breast metastases using a viral gene vector with tumour-selective transcription.

    LENUS (Irish Health Repository)

    Rajendran, Simon

    2012-01-31

    BACKGROUND: Adeno-associated virus (AAV) vectors have significant potential as gene delivery vectors for cancer gene therapy. However, broad AAV2 tissue tropism results in nonspecific gene expression. MATERIALS AND METHODS: We investigated use of the C-X-C chemokine receptor type 4 (CXCR4) promoter to restrict AAV expression to tumour cells, in subcutaneous MCF-7 xenograft mouse models of breast cancer and in patient samples, using bioluminescent imaging and flow cytometric analysis. RESULTS: Higher transgene expression levels were observed in subcutaneous MCF-7 tumours relative to normal tissue (muscle) using the CXCR4 promoter, unlike a ubiquitously expressing Cytomegalovirus promoter construct, with preferential AAVCXCR4 expression in epithelial tumour and CXCR4-positive cells. Transgene expression following intravenously administered AAVCXCR4 in a model of liver metastasis was detected specifically in livers of tumour bearing mice. Ex vivo analysis using patient samples also demonstrated higher AAVCXCR4 expression in tumour compared with normal liver tissue. CONCLUSION: This study demonstrates for the first time, the potential for systemic administration of AAV2 vector for tumour-selective gene therapy.

  16. Around the laboratories: Rutherford: Successful tests on bubble chamber target technique; Stanford (SLAC): New storage rings proposal; Berkeley: The HAPPE project to examine cosmic rays with superconducting magnets; The 60th birthday of Professor N.N. Bogolyubov; Argonne: Performance of the automatic film measuring system POLLY II

    CERN Multimedia

    1969-01-01

    Around the laboratories: Rutherford: Successful tests on bubble chamber target technique; Stanford (SLAC): New storage rings proposal; Berkeley: The HAPPE project to examine cosmic rays with superconducting magnets; The 60th birthday of Professor N.N. Bogolyubov; Argonne: Performance of the automatic film measuring system POLLY II

  17. K-Targeted Metabolomic Analysis Extends Chemical Subtraction to DESIGNER Extracts: Selective Depletion of Extracts of Hops (Humulus lupulus)⊥

    OpenAIRE

    Ramos Alvarenga, René F.; Friesen, J. Brent; Nikolić, Dejan; Simmler, Charlotte; Napolitano, José G.; van Breemen, Richard; Lankin, David C.; McAlpine, James B.; Pauli, Guido F.; Chen, Shao-Nong

    2014-01-01

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid–liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DES...

  18. The solution structures of two soybean calmodulin isoforms provide a structural basis for their selective target activation properties.

    Science.gov (United States)

    Ishida, Hiroaki; Huang, Hao; Yamniuk, Aaron P; Takaya, Yoshiaki; Vogel, Hans J

    2008-05-23

    The intracellular calcium ion is one of the most important secondary messengers in eukaryotic cells. Ca(2+) signals are translated into physiological responses by EF-hand calcium-binding proteins such as calmodulin (CaM). Multiple CaM isoforms occur in plant cells, whereas only a single CaM protein is found in animals. Soybean CaM isoform 1 (sCaM1) shares 90% amino acid sequence identity with animal CaM (aCaM), whereas sCaM4 is only 78% identical. These two sCaM isoforms have distinct target-enzyme activation properties and physiological functions. sCaM4 is highly expressed during the self-defense reaction of the plant and activates the enzyme nitric-oxide synthase (NOS), whereas sCaM1 is incapable of activating NOS. The mechanism of selective target activation by plant CaM isoforms is poorly understood. We have determined high resolution NMR solution structures of Ca(2+)-sCaM1 and -sCaM4. These were compared with previously determined Ca(2+)-aCaM structures. For the N-lobe of the protein, the solution structures of Ca(2+)-sCaM1, -sCaM4, and -aCaM all closely resemble each other. However, despite the high sequence identity with aCaM, the C-lobe of Ca(2+)-sCaM1 has a more open conformation and consequently a larger hydrophobic target-protein binding pocket than Ca(2+)-aCaM or -sCaM4, the presence of which was further confirmed through biophysical measurements. The single Val-144 --> Met substitution in the C-lobe of Ca(2+)-sCaM1, which restores its ability to activate NOS, alters the structure of the C-lobe to a more closed conformation resembling Ca(2+)-aCaM and -sCaM4. The relationships between the structural differences in the two Ca(2+)-sCaM isoforms and their selective target activation properties are discussed. PMID:18347016

  19. Selection of focal earthworm species as non-target soil organisms for environmental risk assessment of genetically modified plants.

    Science.gov (United States)

    van Capelle, Christine; Schrader, Stefan; Arpaia, Salvatore

    2016-04-01

    By means of a literature survey, earthworm species of significant relevance for soil functions in different biogeographical regions of Europe (Atlantic, Boreal, Mediterranean) were identified. These focal earthworm species, defined here according to the EFSA Guidance Document on the environmental risk assessment (ERA) of genetically modified plants, are typical for arable soils under crop rotations with maize and/or potatoes within the three regions represented by Ireland, Sweden and Spain, respectively. Focal earthworm species were selected following a matrix of four steps: Identification of functional groups, categorization of non-target species, ranking species on ecological criteria, and final selection of focal species. They are recommended as appropriate non-target organisms to assess environmental risks of genetically modified (GM) crops; in this case maize and potatoes. In total, 44 literature sources on earthworms in arable cropping systems including maize or potato from Ireland, Sweden and Spain were collected, which present information on species diversity, individual density and specific relevance for soil functions. By means of condensed literature data, those species were identified which (i) play an important functional role in respective soil systems, (ii) are well adapted to the biogeographical regions, (iii) are expected to occur in high abundances under cultivation of maize or potato and (iv) fulfill the requirements for an ERA test system based on life-history traits. First, primary and secondary decomposers were identified as functional groups being exposed to the GM crops. In a second step, anecic and endogeic species were categorized as potential species. In step three, eight anecic and endogeic earthworm species belonging to the family Lumbricidae were ranked as relevant species: Aporrectodea caliginosa, Aporrectodea rosea, Aporrectodea longa, Allolobophora chlorotica, Lumbricus terrestris, Lumbricus friendi, Octodrilus complanatus and

  20. CstF-64 and 3′-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα

    OpenAIRE

    Kandala, Divya T.; Mohan, Nimmy; A, Vivekanand; AP, Sudheesh; G, Reshmi; Laishram, Rakesh S.

    2015-01-01

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3′-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadeny...

  1. Mixed methods evaluation of targeted selective anthelmintic treatment by resource-poor smallholder goat farmers in Botswana.

    Science.gov (United States)

    Walker, Josephine G; Ofithile, Mphoeng; Tavolaro, F Marina; van Wyk, Jan A; Evans, Kate; Morgan, Eric R

    2015-11-30

    Due to the threat of anthelmintic resistance, livestock farmers worldwide are encouraged to selectively apply treatments against gastrointestinal nematodes (GINs). Targeted selective treatment (TST) of individual animals would be especially useful for smallholder farmers in low-income economies, where cost-effective and sustainable intervention strategies will improve livestock productivity and food security. Supporting research has focused mainly on refining technical indicators for treatment, and much less on factors influencing uptake and effectiveness. We used a mixed method approach, whereby qualitative and quantitative approaches are combined, to develop, implement and validate a TST system for GINs in small ruminants, most commonly goats, among smallholder farmers in the Makgadikgadi Pans region of Botswana, and to seek better understanding of system performance within a cultural context. After the first six months of the study, 42 out of 47 enrolled farmers were followed up; 52% had monitored their animals using the taught inspection criteria and 26% applied TST during this phase. Uptake level showed little correlation with farmer characteristics, such as literacy and size of farm. Herd health significantly improved in those herds where anthelmintic treatment was applied: anaemia, as assessed using the five-point FAMACHA(©) scale, was 0.44-0.69 points better (95% confidence interval) and body condition score was 0.18-0.36 points better (95% C.I., five-point scale) in treated compared with untreated herds. Only targeting individuals in greatest need led to similar health improvements compared to treating the entire herd, leading to dose savings ranging from 36% to 97%. This study demonstrates that TST against nematodes can be implemented effectively by resource-poor farmers using a community-led approach. The use of mixed methods provides a promising system to integrate technical and social aspects of TST programmes for maximum uptake and effect. PMID

  2. The ear, the eye, earthquakes and feature selection: listening to automatically generated seismic bulletins for clues as to the differences between true and false events.

    Science.gov (United States)

    Kuzma, H. A.; Arehart, E.; Louie, J. N.; Witzleben, J. L.

    2012-04-01

    Listening to the waveforms generated by earthquakes is not new. The recordings of seismometers have been sped up and played to generations of introductory seismology students, published on educational websites and even included in the occasional symphony. The modern twist on earthquakes as music is an interest in using state-of-the-art computer algorithms for seismic data processing and evaluation. Algorithms such as such as Hidden Markov Models, Bayesian Network models and Support Vector Machines have been highly developed for applications in speech recognition, and might also be adapted for automatic seismic data analysis. Over the last three years, the International Data Centre (IDC) of the Comprehensive Test Ban Treaty Organization (CTBTO) has supported an effort to apply computer learning and data mining algorithms to IDC data processing, particularly to the problem of weeding through automatically generated event bulletins to find events which are non-physical and would otherwise have to be eliminated by the hand of highly trained human analysts. Analysts are able to evaluate events, distinguish between phases, pick new phases and build new events by looking at waveforms displayed on a computer screen. Human ears, however, are much better suited to waveform processing than are the eyes. Our hypothesis is that combining an auditory representation of seismic events with visual waveforms would reduce the time it takes to train an analyst and the time they need to evaluate an event. Since it takes almost two years for a person of extraordinary diligence to become a professional analyst and IDC contracts are limited to seven years by Treaty, faster training would significantly improve IDC operations. Furthermore, once a person learns to distinguish between true and false events by ear, various forms of audio compression can be applied to the data. The compression scheme which yields the smallest data set in which relevant signals can still be heard is likely an

  3. Developing a multi-pollutant conceptual framework for the selection and targeting of interventions in water industry catchment management schemes.

    Science.gov (United States)

    Bloodworth, J W; Holman, I P; Burgess, P J; Gillman, S; Frogbrook, Z; Brown, P

    2015-09-15

    In recent years water companies have started to adopt catchment management to reduce diffuse pollution in drinking water supply areas. The heterogeneity of catchments and the range of pollutants that must be removed to meet the EU Drinking Water Directive (98/83/EC) limits make it difficult to prioritise areas of a catchment for intervention. Thus conceptual frameworks are required that can disaggregate the components of pollutant risk and help water companies make decisions about where to target interventions in their catchments to maximum effect. This paper demonstrates the concept of generalising pollutants in the same framework by reviewing key pollutant processes within a source-mobilisation-delivery context. From this, criteria are developed (with input from water industry professionals involved in catchment management) which highlights the need for a new water industry specific conceptual framework. The new CaRPoW (Catchment Risk to Potable Water) framework uses the Source-Mobilisation-Delivery concept as modular components of risk that work at two scales, source and mobilisation at the field scale and delivery at the catchment scale. Disaggregating pollutant processes permits the main components of risk to be ascertained so that appropriate interventions can be selected. The generic structure also allows for the outputs from different pollutants to be compared so that potential multiple benefits can be identified. CaRPow provides a transferable framework that can be used by water companies to cost-effectively target interventions under current conditions or under scenarios of land use or climate change. PMID:26172105

  4. Practices to optimise gastrointestinal nematode control on sheep, goat and cattle farms in Europe using targeted (selective) treatments.

    Science.gov (United States)

    Charlier, J; Morgan, E R; Rinaldi, L; van Dijk, J; Demeler, J; Höglund, J; Hertzberg, H; Van Ranst, B; Hendrickx, G; Vercruysse, J; Kenyon, F

    2014-09-13

    Due to the development of anthelmintic resistance, there have been calls for more sustainable nematode control practices. Two important concepts were introduced to study and promote the sustainable use of anthelmintics: targeted treatments (TT), where the whole flock/herd is treated based on knowledge of the risk, or parameters that quantify the severity of infection; and targeted selective treatments (TST), where only individual animals within the grazing group are treated. The aim of the TT and TST approaches is to effectively control nematode-induced production impacts while preserving anthelmintic efficacy by maintaining a pool of untreated parasites in refugia. Here, we provide an overview of recent studies that assess the use of TT/TST against gastrointestinal nematodes in ruminants and investigate the economic consequences, feasibility and knowledge gaps associated with TST. We conclude that TT/TST approaches are ready to be used and provide practical benefits today. However, a major shift in mentality will be required to make these approaches common practice in parasite control. PMID:25217603

  5. Measurements of non-target organ doses using MOSFET dosemeters for selected IMRT and 3D CRT radiation treatment procedures.

    Science.gov (United States)

    Wang, Brian; Xu, X George

    2008-01-01

    Many expressed concerns about the potential increase in second cancer risk from the widespread shift to intensity-modulated radiation therapy (IMRT) techniques from traditional 3-D conformal radiation treatment (3D CRT). This paper describes the study on in-phantom measurements of radiation doses in organ sites away from the primary tumour target. The measurements involved a RANDO((R)) phantom and Metal Oxide Semiconductor Field Effect Transistor dosemeters for selected 3D CRT and IMRT treatment plans. Three different treatment plans, 4-field 3D CRT, 6-field 3D CRT and 7-field IMRT for the prostate, were considered in this study. Steps to reconstruct organ doses from directly measured data were also presented. The dosemeter readings showed that the doses decrease as the distances increase for all treatment plans. At 40 cm from the prostate target, doses were <1% of the therapeutic dose. At this location, however, the IMRT plan resulted in an absorbed dose from photons, that is a factor of 3-5 higher than the 3D CRT treatment plans. This increase on absorbed dose is due to the increased exposure time for delivering the IMRT plan. The total monitor unit (MU) was 2850 for the IMRT case, while the MU was 1308 and 1260 for 6-field and 4-field 3D CRT cases, respectively. Findings from this case study involving the prostate treatments agree with those from previous studies that IMRT indeed delivers higher photon doses to locations that are away from the primary target. PMID:17627959

  6. Automatic recognition and validation of the common carotid artery wall segmentation in 100 longitudinal ultrasound images: an integrated approach using feature selection, fitting and classification

    Science.gov (United States)

    Molinari, Filippo; Zeng, Guang; Suri, Jasjit S.

    2010-03-01

    Most of the algorithms for the common carotid artery (CCA) segmentation require human interaction. The aim of this study is to show a novel accurate algorithm for the computer-based automated tracing of CCA in longitudinal B-Mode ultrasound images. One hundred ultrasound B-Mode longitudinal images of the CCA were processed to delineate the region of interest containing the artery. The algorithm is based on geometric feature extraction, line fitting, and classification. Output of the algorithm is the tracings of the near and far adventitia layers. Performance of the algorithm was validated against human tracings (ground truth) and benchmarked with a previously developed automated technique. Ninety-eight images were correctly processed, resulting in an overall system error (with respect to ground truth) equal to 0.18 +/- 0.17 mm (near adventitia) and 0.17 +/- 0.24 mm (far adventitia). In far adventitia detection, our novel technique outperformed the current standard method, which showed overall system errors equal to 0.07 +/- 0.07 mm and 0.49 +/- 0.27 mm for near and far adventitia, respectively. We also showed that our new technique is quite insensitive to noise and has performance independent on the subset of images used for training the classifiers. Superior architecture of this methodology could constitute a general basis for the development of completely automatic CCA segmentation strategies.

  7. Synthetic Cyclolipopeptides Selective against Microbial, Plant and Animal Cell Targets by Incorporation of D-Amino Acids or Histidine

    Science.gov (United States)

    Vilà, Sílvia; Badosa, Esther; Montesinos, Emilio; Planas, Marta; Feliu, Lidia

    2016-01-01

    Cyclolipopeptides derived from the antimicrobial peptide c(Lys-Lys-Leu-Lys-Lys-Phe-Lys-Lys-Leu-Gln) (BPC194) were prepared on solid-phase and screened against four plant pathogens. The incorporation at Lys5 of fatty acids of 4 to 9 carbon atoms led to active cyclolipopeptides. The influence on the antimicrobial activity of the Lys residue that is derivatized was also evaluated. In general, acylation of Lys1, Lys2 or Lys5 rendered the sequences with the highest activity. Incorporation of a D-amino acid maintained the antimicrobial activity while significantly reduced the hemolysis. Replacement of Phe with a His also yielded cyclolipopeptides with low hemolytic activity. Derivatives exhibiting low phytotoxicity in tobacco leaves were also found. Interestingly, sequences with or without significant activity against phytopathogenic bacteria and fungi, but with differential hemolysis and phytotoxicity were identified. Therefore, this study represents an approach to the development of bioactive peptides with selective activity against microbial, plant and animal cell targets. These selective cyclolipopeptides are candidates useful not only to combat plant pathogens but also to be applied in other fields. PMID:27008420

  8. Selective Photothermolysis to target Sebaceous Glands: Theoretical Estimation of Parameters and Preliminary Results Using a Free Electron Laser

    Energy Technology Data Exchange (ETDEWEB)

    Fernanda Sakamoto, Apostolos Doukas, William Farinelli, Zeina Tannous, Michelle D. Shinn, Stephen Benson, Gwyn P. Williams, H. Dylla, Richard Anderson

    2011-12-01

    The success of permanent laser hair removal suggests that selective photothermolysis (SP) of sebaceous glands, another part of hair follicles, may also have merit. About 30% of sebum consists of fats with copious CH2 bond content. SP was studied in vitro, using free electron laser (FEL) pulses at an infrared CH2 vibrational absorption wavelength band. Absorption spectra of natural and artificially prepared sebum were measured from 200 nm to 3000 nm, to determine wavelengths potentially able to target sebaceous glands. The Jefferson National Accelerator superconducting FEL was used to measure photothermal excitation of aqueous gels, artificial sebum, pig skin, human scalp and forehead skin (sebaceous sites). In vitro skin samples were exposed to FEL pulses from 1620 to 1720 nm, spot diameter 7-9.5 mm with exposure through a cold 4C sapphire window in contact with the skin. Exposed and control tissue samples were stained using H and E, and nitroblue tetrazolium chloride staining (NBTC) was used to detect thermal denaturation. Natural and artificial sebum both had absorption peaks near 1210, 1728, 1760, 2306 and 2346 nm. Laser-induced heating of artificial sebum was approximately twice that of water at 1710 and 1720 nm, and about 1.5x higher in human sebaceous glands than in water. Thermal camera imaging showed transient focal heating near sebaceous hair follicles. Histologically, skin samples exposed to {approx}1700 nm, {approx}100-125 ms pulses showed evidence of selective thermal damage to sebaceous glands. Sebaceous glands were positive for NBTC staining, without evidence of selective loss in samples exposed to the laser. Epidermis was undamaged in all samples. Conclusions: SP of sebaceous glands appears to be feasible. Potentially, optical pulses at {approx}1720 nm or {approx}1210 nm delivered with large beam diameter and appropriate skin cooling in approximately 0.1 s may provide an alternative treatment for acne.

  9. Molecular design and structural optimization of potent peptide hydroxamate inhibitors to selectively target human ADAM metallopeptidase domain 17.

    Science.gov (United States)

    Wang, Zhengting; Wang, Lei; Fan, Rong; Zhou, Jie; Zhong, Jie

    2016-04-01

    Human ADAMs (a disintegrin and metalloproteinases) have been established as an attractive therapeutic target of inflammatory disorders such as inflammatory bowel disease (IBD). The ADAM metallopeptidase domain 17 (ADAM17 or TACE) and its close relative ADAM10 are two of the most important ADAM members that share high conservation in sequence, structure and function, but exhibit subtle difference in regulation of downstream cell signaling events. Here, we described a systematic protocol that combined computational modeling and experimental assay to discover novel peptide hydroxamate derivatives as potent and selective inhibitors for ADAM17 over ADAM10. In the procedure, a virtual combinatorial library of peptide hydroxamate compounds was generated by exploiting intermolecular interactions involved in crystal and modeled structures. The library was examined in detail to identify few promising candidates with both high affinity to ADAM17 and low affinity to ADAM10, which were then tested in vitro with enzyme inhibition assay. Consequently, two peptide hydroxamates Hxm-Phe-Ser-Asn and Hxm-Phe-Arg-Gln were found to exhibit potent inhibition against ADAM17 (Ki=92 and 47nM, respectively) and strong selectivity for ADAM17 over ADAM10 (∼7-fold and ∼5-fold, S=0.86 and 0.71, respectively). The structural basis and energetic property of ADAM17 and ADAM10 interactions with the designed inhibitors were also investigated systematically. It is found that the exquisite network of nonbonded interactions involving the side chains of peptide hydroxamates is primarily responsible for inhibitor selectivity, while the coordination interactions and hydrogen bonds formed by the hydroxamate moiety and backbone of peptide hydroxamates confer high affinity to inhibitor binding. PMID:26709988

  10. Target-Date Funds in 401(k) Retirement Plans

    OpenAIRE

    Mitchell, Olivia S.; Stephen Utkus

    2012-01-01

    Individual responsibility for portfolio construction is a central theme for defined contribution pensions, yet the rise of target-date funds is shifting investment decisions from workers back to employers. A complex choice architecture including automatic enrollment, reenrollment, and fund mapping, is increasing the number of participants defaulting into employer-selected target-date funds. At the same time, portfolios of non-defaulted participants undergo sizeable changes, with equity share ...

  11. An approach to the construction of tailor-made amphiphilic peptides that strongly and selectively bind to hairpin RNA targets.

    Science.gov (United States)

    Lee, Su Jin; Hyun, Soonsil; Kieft, Jeffrey S; Yu, Jaehoon

    2009-02-18

    strategies that can be used to prepare peptides that both strongly and selectively target hairpin RNAs. Specifically, the findings indicate that tailor-made amphiphilic peptide ligands against certain hairpin RNAs can be obtained if the RNA target possesses a deep groove in which both the hydrophobic and hydrophilic spheres of the peptide interact. PMID:19199621

  12. Automatic processing of dominance and submissiveness

    OpenAIRE

    Moors, Agnes; De Houwer, Jan

    2005-01-01

    We investigated whether people are able to detect in a relatively automatic manner the dominant or submissive status of persons engaged in social interactions. Using a variant of the affective Simon task (De Houwer & Eelen, 1998), we demonstrated that the verbal response DOMINANT or SUBMISSIVE was facilitated when it had to be made to a target person that was respectively dominant or submissive. These results provide new information about the automatic nature of appraisals and ...

  13. Optimization of radiotherapy to target volumes with concave outlines: target-dose homogenization and selective sparing of critical structures by constrained matrix inversion

    International Nuclear Information System (INIS)

    The design of 3D-conformal dose distributions for targets with concave outlines is a technical challenge in conformal radiotherapy. For these targets, it is impossible to find beam incidences for which the target volume can be isolated from the tissues at risk. Commonly occurring examples are most thyroid cancers and the targets located at the lower neck and upper mediastinal levels related to some head and neck. A solution to this problem was developed, using beam intensity modulation executed with a multileaf collimator by applying a static beam-segmentation technique. The method includes the definition of beam incidences and beam segments of specific shape as well as the calculation of segment weights. Tests on Sherouse's GRATISTM planning system allowed to escalate the dose to these targets to 65-70 Gy without exceeding spinal cord tolerance. Further optimization by constrained matrix inversion was investigated to explore the possibility of further dose escalation

  14. Optimization of radiotherapy to target volumes with concave outlines: target-dose homogenization and selective sparing of critical structures by constrained matrix inversion

    Energy Technology Data Exchange (ETDEWEB)

    Colle, C.; Van den Berge, D.; De Wagter, C.; Fortan, L.; Van Duyse, B.; De Neve, W.

    1995-12-01

    The design of 3D-conformal dose distributions for targets with concave outlines is a technical challenge in conformal radiotherapy. For these targets, it is impossible to find beam incidences for which the target volume can be isolated from the tissues at risk. Commonly occurring examples are most thyroid cancers and the targets located at the lower neck and upper mediastinal levels related to some head and neck. A solution to this problem was developed, using beam intensity modulation executed with a multileaf collimator by applying a static beam-segmentation technique. The method includes the definition of beam incidences and beam segments of specific shape as well as the calculation of segment weights. Tests on Sherouse`s GRATISTM planning system allowed to escalate the dose to these targets to 65-70 Gy without exceeding spinal cord tolerance. Further optimization by constrained matrix inversion was investigated to explore the possibility of further dose escalation.

  15. Online select feature and occlusion processing target tracking%在线特征选择和遮挡处理的目标跟踪

    Institute of Scientific and Technical Information of China (English)

    杨心力; 杨恢先; 冷爱莲

    2011-01-01

    In order to improve the robustness of tracking system under complex surrounding such as similar object interference, illumination change, this paper proposed that employing Fisher criteria online selecting color feature mechanism, which was embedded in target tracking algorithm. However, when the target was severely occluded, still online selecting discriminative feature, would make target template offset, and lead to tracking failure. In order to select discriminative feature in the case of tracked target was severely occluded, selected a reliable sub-region of the occluded target and utilized reliable sub-region infer the color feature of the occluded target area, then online selected color feature. Experimental results show that this paper proposed method can greatly improve the robustness of target tracking method under complex surrounding such as similar to object interference, tracked target being occluded.%为了提高相似物体干扰、光照变化等复杂环境下目标跟踪的稳定性,提出利用Fisher准则的在线选择鉴别性特征,将在线特征选择嵌入到跟踪算法中.但是,在目标被严重遮挡时仍在线选择鉴别性特征,会使目标模板偏移,导致跟踪失败.为了在目标被严重遮挡的情况下仍能在线选择鉴别性目标特征,选择一个可靠的子区域来推测被遮挡目标的颜色特征,再选择鉴别性特征.实验结果表明该方法在相似物体干扰、被跟踪目标被遮挡等复杂环境下极大地改善了跟踪的稳定性.

  16. AUTOMATIC DESIGNING OF POWER SUPPLY SYSTEMS

    Directory of Open Access Journals (Sweden)

    A. I. Kirspou

    2016-01-01

    Full Text Available Development of automatic designing system for power supply of industrial enterprises is considered in the paper. Its complete structure and principle of operation are determined and established. Modern graphical interface and data scheme are developed, software is completely realized. Methodology and software correspond to the requirements of the up-to-date designing, describe a general algorithm of program process and also reveals properties of automatic designing system objects. Automatic designing system is based on module principle while using object-orientated programming. Automatic designing system makes it possible to carry out consistently designing calculations of power supply system and select the required equipment with subsequent output of all calculations in the form of explanatory note. Automatic designing system can be applied by designing organizations under conditions of actual designing.

  17. Distributed image processing for automatic target recognition

    Science.gov (United States)

    Cozien, Roger F.

    2001-02-01

    Our purpose is, in medium term, to detect in air images, characteristic shapes and objects such as airports, industrial plants, planes, tanks, trucks, . with great accuracy and low rate of mistakes. However, we also want to value whether the link between neural networks and multi-agents systems is relevant and effective. If it appears to be really effective, we hope to use this kind of technology in other fields. That would be an easy and convenient way to depict and to use the agents' knowledge which is distributed and fragmented. After a first phase of preliminary tests to know if agents are able to give relevant information to a neural network, we verify that only a few agents running on an image are enough to inform the network and let it generalize the agents' distributed and fragmented knowledge. In a second phase, we developed a distributed architecture allowing several multi-agents systems running at the same time on different computers with different images. All those agents send information to a "multi neural networks system" whose job is to identify the shapes detected by the agents. The name we gave to our project is Jarod.

  18. ANALYSIS OF EXISTING AND PROSPECTIVE TECHNICAL CONTROL SYSTEMS OF NUMERIC CODES AUTOMATIC BLOCKING

    Directory of Open Access Journals (Sweden)

    A. M. Beznarytnyy

    2013-09-01

    Full Text Available Purpose. To identify the characteristic features of the engineering control measures system of automatic block of numeric code, identifying their advantages and disadvantages, to analyze the possibility of their use in the problems of diagnosing status of the devices automatic block and setting targets for the development of new diagnostic systems. Methodology. In order to achieve targets the objective theoretical and analytical method and the method of functional analysis have been used. Findings. The analysis of existing and future facilities of the remote control and diagnostics automatic block devices had shown that the existing systems of diagnosis were not sufficiently informative, designed primarily to control the discrete parameters, which in turn did not allow them to construct a decision support subsystem. In developing of new systems of technical diagnostics it was proposed to use the principle of centralized distributed processing of diagnostic data, to include a subsystem support decision-making in to the diagnostics system, it will reduce the amount of work to maintain the devices blocking and reduce recovery time after the occurrence injury. Originality. As a result, the currently existing engineering controls facilities of automatic block can not provide a full assessment of the state distillation alarms and locks. Criteria for the development of new systems of technical diagnostics with increasing amounts of diagnostic information and its automatic analysis were proposed. Practical value. These results of the analysis can be used in practice in order to select the technical control of automatic block devices, as well as the further development of diagnostic systems automatic block that allows for a gradual transition from a planned preventive maintenance service model to the actual state of the monitored devices.

  19. Attenuation-based automatic kilovolt (kV)-selection in computed tomography of the chest: Effects on radiation exposure and image quality

    Energy Technology Data Exchange (ETDEWEB)

    Eller, Achim; Wuest, Wolfgang; Scharf, Michael; Brand, Michael [Department of Radiology, University Erlangen (Germany); Achenbach, Stephan [Department of Cardiology, University Erlangen (Germany); Uder, Michael [Department of Radiology, University Erlangen (Germany); Imaging Science Institute, Erlangen (Germany); Lell, Michael M., E-mail: Michael.lell@uk-erlangen.de [Department of Radiology, University Erlangen (Germany); Imaging Science Institute, Erlangen (Germany)

    2013-12-01

    Objectives: To evaluate an automated attenuation-based kV-selection in computed tomography of the chest in respect to radiation dose and image quality, compared to a standard 120 kV protocol. Materials and methods: 104 patients were examined using a 128-slice scanner. Fifty examinations (58 ± 15 years, study group) were performed using the automated adaption of tube potential (100–140 kV), based on the attenuation profile of the scout scan, 54 examinations (62 ± 14 years, control group) with fixed 120 kV. Estimated CT dose index (CTDI) of the software-proposed setting was compared with a 120 kV protocol. After the scan CTDI volume (CTDIvol) and dose length product (DLP) were recorded. Image quality was assessed by region of interest (ROI) measurements, subjective image quality by two observers with a 4-point scale (3 – excellent, 0 – not diagnostic). Results: The algorithm selected 100 kV in 78% and 120 kV in 22%. Overall CTDIvol reduction was 26.6% (34% in 100 kV) overall DLP reduction was 22.8% (32.1% in 100 kV) (all p < 0.001). Subjective image quality was excellent in both groups. Conclusion: The attenuation based kV-selection algorithm enables relevant dose reduction (∼27%) in chest-CT while keeping image quality parameters at high levels.

  20. Attenuation-based automatic kilovolt (kV)-selection in computed tomography of the chest: Effects on radiation exposure and image quality

    International Nuclear Information System (INIS)

    Objectives: To evaluate an automated attenuation-based kV-selection in computed tomography of the chest in respect to radiation dose and image quality, compared to a standard 120 kV protocol. Materials and methods: 104 patients were examined using a 128-slice scanner. Fifty examinations (58 ± 15 years, study group) were performed using the automated adaption of tube potential (100–140 kV), based on the attenuation profile of the scout scan, 54 examinations (62 ± 14 years, control group) with fixed 120 kV. Estimated CT dose index (CTDI) of the software-proposed setting was compared with a 120 kV protocol. After the scan CTDI volume (CTDIvol) and dose length product (DLP) were recorded. Image quality was assessed by region of interest (ROI) measurements, subjective image quality by two observers with a 4-point scale (3 – excellent, 0 – not diagnostic). Results: The algorithm selected 100 kV in 78% and 120 kV in 22%. Overall CTDIvol reduction was 26.6% (34% in 100 kV) overall DLP reduction was 22.8% (32.1% in 100 kV) (all p < 0.001). Subjective image quality was excellent in both groups. Conclusion: The attenuation based kV-selection algorithm enables relevant dose reduction (∼27%) in chest-CT while keeping image quality parameters at high levels

  1. Long-gradient separations coupled with selected reaction monitoring for highly sensitive, large scale targeted protein quantification in a single analysis

    OpenAIRE

    Shi, Tujin; Fillmore, Thomas L.; Gao, Yuqian; Zhao, Rui; He, Jintang; Schepmoes, Athena A.; Nicora, Carrie D.; Wu, Chaochao; Chambers, Justin L.; Moore, Ronald J.; Kagan, Jacob; Srivastava, Sudhir; Liu, Alvin Y; Rodland, Karin D.; Liu, Tao

    2013-01-01

    Long-gradient separations coupled to tandem MS were recently demonstrated to provide a deep proteome coverage for global proteomics; however, such long-gradient separations have not been explored for targeted proteomics. Herein, we investigate the potential performance of the long-gradient separations coupled with selected reaction monitoring (LG-SRM) for targeted protein quantification. Direct comparison of LG-SRM (5 h gradient) and conventional LC-SRM (45 min gradient) showed that the long-...

  2. Parallel reaction monitoring (PRM) and selected reaction monitoring (SRM) exhibit comparable linearity, dynamic range and precision for targeted quantitative HDL proteomics

    OpenAIRE

    Ronsein, Graziella E.; Pamir, Nathalie; von Haller, Priska D.; Kim, Daniel S.; Oda, Michael N.; Jarvik, Gail P.; Vaisar, Tomas; Heinecke, Jay W.

    2014-01-01

    High-density lipoprotein (HDL), a lipid nanoparticle containing many different low abundance proteins, is an attractive target for clinical proteomics because its compositional heterogeneity is linked to its cardioprotective effects. Selected reaction monitoring (SRM) is currently the method of choice for targeted quantification of proteins in such a complex biological matrix. However, model system studies suggest that parallel reaction monitoring (PRM) is more specific than SRM because many ...

  3. Non-targeted detection of chemical contamination in carbonated soft drinks using NMR spectroscopy, variable selection and chemometrics

    Energy Technology Data Exchange (ETDEWEB)

    Charlton, Adrian J. [Department for Environment, Food and Rural Affairs, Central Science Laboratory, Sand Hutton, York YO41 1LZ (United Kingdom)], E-mail: adrian.charlton@csl.gov.uk; Robb, Paul; Donarski, James A.; Godward, John [Department for Environment, Food and Rural Affairs, Central Science Laboratory, Sand Hutton, York YO41 1LZ (United Kingdom)

    2008-06-23

    An efficient method for detecting malicious and accidental contamination of foods has been developed using a combined {sup 1}H nuclear magnetic resonance (NMR) and chemometrics approach. The method has been demonstrated using a commercially available carbonated soft drink, as being capable of identifying atypical products and to identify contaminant resonances. Soft-independent modelling of class analogy (SIMCA) was used to compare {sup 1}H NMR profiles of genuine products (obtained from the manufacturer) against retail products spiked in the laboratory with impurities. The benefits of using feature selection for extracting contaminant NMR frequencies were also assessed. Using example impurities (paraquat, p-cresol and glyphosate) NMR spectra were analysed using multivariate methods resulting in detection limits of approximately 0.075, 0.2, and 0.06 mM for p-cresol, paraquat and glyphosate, respectively. These detection limits are shown to be approximately 100-fold lower than the minimum lethal dose for paraquat. The methodology presented here is used to assess the composition of complex matrices for the presence of contaminating molecules without a priori knowledge of the nature of potential contaminants. The ability to detect if a sample does not fit into the expected profile without recourse to multiple targeted analyses is a valuable tool for incident detection and forensic applications.

  4. Non-targeted detection of chemical contamination in carbonated soft drinks using NMR spectroscopy, variable selection and chemometrics

    International Nuclear Information System (INIS)

    An efficient method for detecting malicious and accidental contamination of foods has been developed using a combined 1H nuclear magnetic resonance (NMR) and chemometrics approach. The method has been demonstrated using a commercially available carbonated soft drink, as being capable of identifying atypical products and to identify contaminant resonances. Soft-independent modelling of class analogy (SIMCA) was used to compare 1H NMR profiles of genuine products (obtained from the manufacturer) against retail products spiked in the laboratory with impurities. The benefits of using feature selection for extracting contaminant NMR frequencies were also assessed. Using example impurities (paraquat, p-cresol and glyphosate) NMR spectra were analysed using multivariate methods resulting in detection limits of approximately 0.075, 0.2, and 0.06 mM for p-cresol, paraquat and glyphosate, respectively. These detection limits are shown to be approximately 100-fold lower than the minimum lethal dose for paraquat. The methodology presented here is used to assess the composition of complex matrices for the presence of contaminating molecules without a priori knowledge of the nature of potential contaminants. The ability to detect if a sample does not fit into the expected profile without recourse to multiple targeted analyses is a valuable tool for incident detection and forensic applications

  5. Integration of Affinity Selection-Mass Spectrometry and Functional Cell-Based Assays to Rapidly Triage Druggable Target Space within the NF-κB Pathway.

    Science.gov (United States)

    Kutilek, Victoria D; Andrews, Christine L; Richards, Matthew P; Xu, Zangwei; Sun, Tianxiao; Chen, Yiping; Hashke, Andrew; Smotrov, Nadya; Fernandez, Rafael; Nickbarg, Elliott B; Chamberlin, Chad; Sauvagnat, Berengere; Curran, Patrick J; Boinay, Ryan; Saradjian, Peter; Allen, Samantha J; Byrne, Noel; Elsen, Nathaniel L; Ford, Rachael E; Hall, Dawn L; Kornienko, Maria; Rickert, Keith W; Sharma, Sujata; Shipman, Jennifer M; Lumb, Kevin J; Coleman, Kevin; Dandliker, Peter J; Kariv, Ilona; Beutel, Bruce

    2016-07-01

    The primary objective of early drug discovery is to associate druggable target space with a desired phenotype. The inability to efficiently associate these often leads to failure early in the drug discovery process. In this proof-of-concept study, the most tractable starting points for drug discovery within the NF-κB pathway model system were identified by integrating affinity selection-mass spectrometry (AS-MS) with functional cellular assays. The AS-MS platform Automated Ligand Identification System (ALIS) was used to rapidly screen 15 NF-κB proteins in parallel against large-compound libraries. ALIS identified 382 target-selective compounds binding to 14 of the 15 proteins. Without any chemical optimization, 22 of the 382 target-selective compounds exhibited a cellular phenotype consistent with the respective target associated in ALIS. Further studies on structurally related compounds distinguished two chemical series that exhibited a preliminary structure-activity relationship and confirmed target-driven cellular activity to NF-κB1/p105 and TRAF5, respectively. These two series represent new drug discovery opportunities for chemical optimization. The results described herein demonstrate the power of combining ALIS with cell functional assays in a high-throughput, target-based approach to determine the most tractable drug discovery opportunities within a pathway. PMID:26969322

  6. Validation, optimisation, and application data in support of the development of a targeted selected ion monitoring assay for degraded cardiac troponin T.

    Science.gov (United States)

    Streng, Alexander S; de Boer, Douwe; Bouwman, Freek G; Mariman, Edwin C M; Scholten, Arjen; van Dieijen-Visser, Marja P; Wodzig, Will K W H

    2016-06-01

    Cardiac troponin T (cTnT) fragmentation in human serum was investigated using a newly developed targeted selected ion monitoring assay, as described in the accompanying article: "Development of a targeted selected ion monitoring assay for the elucidation of protease induced structural changes in cardiac troponin T" [1]. This article presents data describing aspects of the validation and optimisation of this assay. The data consists of several figures, an excel file containing the results of a sequence identity search, and a description of the raw mass spectrometry (MS) data files, deposited in the ProteomeXchange repository with id PRIDE: PXD003187. PMID:26977445

  7. 面向纸质胸环靶的自动识别报靶系统研究%Automatic Recognization Target-reading System for Chest Silhouette of Paper

    Institute of Scientific and Technical Information of China (English)

    刘瑞香; 刘天时; 王洪伟

    2015-01-01

    为了克服在靶场射击训练中人工报靶消耗大量的人力和时间的同时还存在诸多隐患,如误报和谎报等,本文设计了一套硬件配置相对简单、性能稳定可靠、判靶精准快速的面向纸质胸环靶的自动识别报靶系统。该系统结合嵌入式技术、图像处理技术、有线以及无线网络传输技术,实现快速检测靶面信息以及弹孔坐标。在图像处理的基础上,对图像使用区域特征消除法对干扰背景进行了消除,同时采用灰度双向肖波投影确定靶心位置,提取出靶面图像的所有有效特征信息。通过嵌入式终端、wifi通信以及网络传输等完成了整个系统的搭建。本系统具有高效、快速和判靶精准等特点。%This paper proposes an automatic recognition target-scoring system for chest bitmap with simple hardware requirement, stable and reliable performance, precise and fast scoring in order to overcome the problems that the artificial counting consumes a lot of manpower, time and also there are many dangers in shooting training, such as the misinformation and the misrepresentation. Combining with the embedded technology, image processing technology, wired and wireless network transmission technology, the system implements the detecting of target surface information rapidly and the coordinates of bullet holes. The regional feature re⁃moving method is employed to eliminate background interference, and the grey two-direction clipping projection is also taken to de⁃termine bull's eye position based on the original picture processing. Finally, all characteristic information of the image is extracted effectively. The system is built through the embedded terminal, WiFi communication and network transmission. It has the charac⁃teristics of efficient, fast and good scoring precision.

  8. Automatic Recognization Target-reading System for Chest Silhouette of Paper%面向纸质胸环靶的自动识别报靶系统研究

    Institute of Scientific and Technical Information of China (English)

    刘瑞香; 刘天时; 王洪伟

    2015-01-01

    为了克服在靶场射击训练中人工报靶消耗大量的人力和时间的同时还存在诸多隐患,如误报和谎报等,本文设计了一套硬件配置相对简单、性能稳定可靠、判靶精准快速的面向纸质胸环靶的自动识别报靶系统。该系统结合嵌入式技术、图像处理技术、有线以及无线网络传输技术,实现快速检测靶面信息以及弹孔坐标。在图像处理的基础上,对图像使用区域特征消除法对干扰背景进行了消除,同时采用灰度双向肖波投影确定靶心位置,提取出靶面图像的所有有效特征信息。通过嵌入式终端、wifi通信以及网络传输等完成了整个系统的搭建。本系统具有高效、快速和判靶精准等特点。%This paper proposes an automatic recognition target-scoring system for chest bitmap with simple hardware requirement, stable and reliable performance, precise and fast scoring in order to overcome the problems that the artificial counting consumes a lot of manpower, time and also there are many dangers in shooting training, such as the misinformation and the misrepresentation. Combining with the embedded technology, image processing technology, wired and wireless network transmission technology, the system implements the detecting of target surface information rapidly and the coordinates of bullet holes. The regional feature re⁃moving method is employed to eliminate background interference, and the grey two-direction clipping projection is also taken to de⁃termine bull's eye position based on the original picture processing. Finally, all characteristic information of the image is extracted effectively. The system is built through the embedded terminal, WiFi communication and network transmission. It has the charac⁃teristics of efficient, fast and good scoring precision.

  9. An interdisciplinary analysis of multispectral satellite data for selected cover types in the Colorado Mountains, using automatic data processing techniques. [geological lineaments and mineral exploration

    Science.gov (United States)

    Hoffer, R. M. (Principal Investigator)

    1974-01-01

    The author has identified the following significant results. One capability which has been recognized by many geologists working with space photography is the ability to see linear features and alinements which were previously not apparent. To the exploration geologist, major lineaments seen on satellite images are of particular interest. A portion of ERTS-1 frame 1407-17193 (3 Sept. 1973) was used for mapping lineaments and producing an iso-lineament intersection map. Skylab photography over the area of prime area was not useable due to snow cover. Once the lineaments were mapped, a grid with 2.5 km spacing was overlayed on the map and the lineament intersections occurring within each grid square were counted and the number plotted in the center of the grid square. These numbers were then contoured producing a contour map of equal lineament intersection. It is believed that the areas of high intersection concentration would be the most favorable area for ore mineralization if favorable host rocks are also present. These highly fractured areas would act as conduits for carrying the ore forming solutions to the site of deposition in a favorable host rock. Two of the six areas of high intersection concentration are over areas of present or past mining camps and small claims are known to exist near the others. These would be prime target areas for future mineral exploration.

  10. Automatic input rectification

    OpenAIRE

    Long, Fan; Ganesh, Vijay; Carbin, Michael James; Sidiroglou, Stelios; Rinard, Martin

    2012-01-01

    We present a novel technique, automatic input rectification, and a prototype implementation, SOAP. SOAP learns a set of constraints characterizing typical inputs that an application is highly likely to process correctly. When given an atypical input that does not satisfy these constraints, SOAP automatically rectifies the input (i.e., changes the input so that it satisfies the learned constraints). The goal is to automatically convert potentially dangerous inputs into typical inputs that the ...

  11. Automatic Fiscal Stabilizers

    Directory of Open Access Journals (Sweden)

    Narcis Eduard Mitu

    2013-11-01

    Full Text Available Policies or institutions (built into an economic system that automatically tend to dampen economic cycle fluctuations in income, employment, etc., without direct government intervention. For example, in boom times, progressive income tax automatically reduces money supply as incomes and spendings rise. Similarly, in recessionary times, payment of unemployment benefits injects more money in the system and stimulates demand. Also called automatic stabilizers or built-in stabilizers.

  12. Automatic differentiation bibliography

    Energy Technology Data Exchange (ETDEWEB)

    Corliss, G.F. (comp.)

    1992-07-01

    This is a bibliography of work related to automatic differentiation. Automatic differentiation is a technique for the fast, accurate propagation of derivative values using the chain rule. It is neither symbolic nor numeric. Automatic differentiation is a fundamental tool for scientific computation, with applications in optimization, nonlinear equations, nonlinear least squares approximation, stiff ordinary differential equation, partial differential equations, continuation methods, and sensitivity analysis. This report is an updated version of the bibliography which originally appeared in Automatic Differentiation of Algorithms: Theory, Implementation, and Application.

  13. Which is the best phenotypic trait for use in a targeted selective treatment strategy for growing lambs in temperate climates?

    Science.gov (United States)

    Laurenson, Yan C S M; Kahn, Lewis P; Bishop, Stephen C; Kyriazakis, Ilias

    2016-08-15

    Targeted selective treatment (TST) requires the ability to identify the animals for which anthelmintic treatment will result in the greatest benefit to the entire flock. Various phenotypic traits have previously been suggested as determinant criteria for TST; however, the weight gain benefit and impact on anthelmintic efficacy for each determinant criterion is expected to be dependent upon the level of nematode challenge and the timing of anthelmintic treatment. A mathematical model was used to simulate a population of 10,000 parasitologically naïve Scottish Blackface lambs (with heritable variation in host-parasite interactions) grazing on medium-quality pasture (grazing density=30 lambs/ha, crude protein=140g/kg DM, metabolisable energy=10MJ/kg DM) with an initial larval contamination of 1000, 3000 or 5000 Teladorsagia circumcincta L3/kg DM. Anthelmintic drenches were administered to 0, 50 or 100% of the population on a single occasion. The day of anthelmintic treatment was independently modelled for every day within the 121day simulation. Where TST scenarios were simulated (50% treated), lambs were either chosen by random selection or according to highest faecal egg count (FEC, eggs/g DM faeces), lowest live weight (LW, kg) or lowest growth rate (kg/day). Average lamb empty body weight (kg) and the resistance (R) allele frequency amongst the parasite population on pasture were recorded at slaughter (day 121) for each scenario. Average weight gain benefit and increase in R allele frequency for each determinant criterion, level of initial larval contamination and day of anthelmintic treatment were calculated by comparison to a non-treated population. Determinant criteria were evaluated according to average weight gain benefit divided by increase in R allele frequency to determine the benefit per R. Whilst positive phenotypic correlations were predicted between worm burden and FEC; using LW as the determinant criterion provided the greatest benefit per R for all

  14. Weight gain-based targeted selective treatments (TST) of gastrointestinal nematodes in first-season grazing cattle.

    Science.gov (United States)

    Höglund, Johan; Dahlström, Frida; Sollenberg, Sofia; Hessle, Anna

    2013-09-23

    A three-year trial was performed in south-western Sweden to compare animal performance and levels of parasite control in three grazing groups, each with 18-24 first-season grazing (FSG) calves in similar set-stocked pasture enclosures. These groups were subjected to: (1) no parasite control (NT), (2) monthly repeated doramectin (Dectomax(®)) injections (SP), or (3) targeted selective weight gain-based anthelmintic treatments (TST) but only when individual calf performance was inferior to the average of the poorer 50% of those calves in group SP. In each year, weight and parasitological variables were measured at turn-out and then at predetermined intervals for 22-24 weeks during the grazing season. The dewormed calves in group SP had a higher average weight gain at housing (range 0.39-0.61 kg/day) than those in TST (0.36-0.50 kg/day), which in turn always exceeded the NT group (0.23-0.42 kg/day). This indicates that the parasite challenge in the NT group was sufficiently high to result in production loss. However, the average cumulative faecal egg counts (FEC) at housing in NT were in the range 1271-1953 eggs per gram faeces (epg) and in TST 1221-1968 epg. In contrast, parasite eggs were rarely recorded in group SP and then only during the first two years (on average 12 and 38 epg). There were also no significant differences in FEC or serum pepsinogen levels between FSG in groups NT and TST. The animals in SP received 7 doses of doramectin each year, whereas those in TST received an average of 0.5 doses. Thus, the TST approach represented a 92% reduction in anthelmintic use. The average weight gain in animals subjected to TST was always significantly lower than in animals dewormed regularly. In addition, there were no signs of short-term selection for anthelmintic resistance in the group SP animals, despite the fairly intensive use of injectable doramectin. PMID:23608034

  15. Automatic contrast: evidence that automatic comparison with the social self affects evaluative responses.

    Science.gov (United States)

    Ruys, Kirsten I; Spears, Russell; Gordijn, Ernestine H; de Vries, Nanne K

    2007-08-01

    The aim of the present research was to investigate whether unconsciously presented affective information may cause opposite evaluative responses depending on what social category the information originates from. We argue that automatic comparison processes between the self and the unconscious affective information produce this evaluative contrast effect. Consistent with research on automatic behaviour, we propose that when an intergroup context is activated, an automatic comparison to the social self may determine the automatic evaluative responses, at least for highly visible categories (e.g. sex, ethnicity). Contrary to previous research on evaluative priming, we predict automatic contrastive responses to affective information originating from an outgroup category such that the evaluative response to neutral targets is opposite to the valence of the suboptimal primes. Two studies using different intergroup contexts provide support for our hypotheses. PMID:17705936

  16. Selection of binding targets in parasites using phage-display and aptamer libraries in vivo and in vitro

    Directory of Open Access Journals (Sweden)

    Renata Rosito Tonelli

    2013-01-01

    Full Text Available Parasite infections are largely dependent on interactions between pathogen and different host cell populations to guarantee a successful infectious process. This is particularly true for obligatory intracellular parasites as Plasmodium, Toxoplasma, Leishmania, to name a few. Adhesion to and entry into the cell are essential steps requiring specific parasite and host cell molecules. The large amount of possible involved molecules poses additional difficulties for their identification by the classical biochemical approaches. In this respect, the search for alternative techniques should be pursued. Among them two powerful methodologies can be employed, both relying upon the construction of highly diverse combinatorial libraries of peptides or oligonucleotides that randomly bind with high affinity to targets on the cell surface and are selectively displaced by putative ligands. These are, respectively, the peptide-based phage display and the oligonucleotide-based aptamer techniques.The phage display technique has been extensively employed for the identification of novel ligands in vitro and in vivo in different areas such as cancer, vaccine development and epitope mapping. Particularly, phage display has been employed in the investigation of pathogen-host interactions. Although this methodology has been used for some parasites with encouraging results, in trypanosomatids its use is, as yet, scanty. RNA and DNA aptamers, developed by the SELEX process (Systematic Evolution of Ligands by Exponential Enrichment, were described over two decades ago and since then contributed to a large number of structured nucleic acids for diagnostic or therapeutic purposes or for the understanding of the cell biology. Similarly to the phage display technique scarce use of the SELEX process has been used in the probing of parasite-host interaction.In this review, an overall survey on the use of both phage display and aptamer technologies in different pathogenic

  17. Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson's Disease

    Institute of Scientific and Technical Information of China (English)

    Xiao-Houg Wang; Lin Zhang; Laura Sperry; John Olichney; Sarah Tomaszewski Farias; Kiarash Shahlaie; Norika Malhado Chang

    2015-01-01

    Objective: This review examines the evidence that deep brain stimulation (DBS) has extensive impact on nonmotor symptoms (NMSs) of patients with Parkinson's disease (PD).Data Sources: We retrieved information from the PubMed database up to September, 2015, using various search terms and their combinations including PD, NMSs, DBS, globus pallidus intemus (GPi), subthalamic nucleus (STN), and ventral intermediate thalamic nucleus.Study Selection: We included data from peer-reviewed journals on impacts of DBS on neuropsychological profiles, sensory function, autonomic symptoms, weight changes, and sleep disturbances.For psychological symptoms and cognitive impairment, we tried to use more reliable proofs: Random, control, multicenter, large sample sizes, and long period follow-up clinical studies.We categorized the NMSs into four groups: those that would improve definitively following DBS;those that are not significantly affected by DBS;those that remain controversial on their surgical benefit;and those that can be worsened by DBS.Results: In general, it seems to be an overall beneficial effect of DBS on NMSs, such as sensory, sleep, gastrointestinal, sweating, cardiovascular, odor, urological symptoms, and sexual dysfunction, GPi-DBS may produce similar results;Both STN and Gpi-DBS are safe with regard to cognition and psychology over long-term follow-up, though verbal fluency decline is related to DBS;The impact of DBS on behavioral addictions and dysphagia is still uncertain.Conclusions: As the motor effects of STN-DBS and GPi-DBS are similar, NMSs may determine the target choice in surgery of future patients.

  18. CstF-64 and 3'-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα.

    Science.gov (United States)

    Kandala, Divya T; Mohan, Nimmy; A, Vivekanand; A P, Sudheesh; G, Reshmi; Laishram, Rakesh S

    2016-01-29

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3'-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3'-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3'-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3'-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. PMID:26496945

  19. CstF-64 and 3′-UTR cis-element determine Star-PAP specificity for target mRNA selection by excluding PAPα

    Science.gov (United States)

    Kandala, Divya T.; Mohan, Nimmy; A, Vivekanand; AP, Sudheesh; G, Reshmi; Laishram, Rakesh S.

    2016-01-01

    Almost all eukaryotic mRNAs have a poly (A) tail at the 3′-end. Canonical PAPs (PAPα/γ) polyadenylate nuclear pre-mRNAs. The recent identification of the non-canonical Star-PAP revealed specificity of nuclear PAPs for pre-mRNAs, yet the mechanism how Star-PAP selects mRNA targets is still elusive. Moreover, how Star-PAP target mRNAs having canonical AAUAAA signal are not regulated by PAPα is unclear. We investigate specificity mechanisms of Star-PAP that selects pre-mRNA targets for polyadenylation. Star-PAP assembles distinct 3′-end processing complex and controls pre-mRNAs independent of PAPα. We identified a Star-PAP recognition nucleotide motif and showed that suboptimal DSE on Star-PAP target pre-mRNA 3′-UTRs inhibit CstF-64 binding, thus preventing PAPα recruitment onto it. Altering 3′-UTR cis-elements on a Star-PAP target pre-mRNA can switch the regulatory PAP from Star-PAP to PAPα. Our results suggest a mechanism of poly (A) site selection that has potential implication on the regulation of alternative polyadenylation. PMID:26496945

  20. Application Accuracy of Automatic Registration in Frameless Stereotaxy

    OpenAIRE

    Rachinger, Jens; Keller, Boris von; Ganslandt, Oliver; Fahlbusch, Rudolf; Nimsky, Christopher

    2013-01-01

    Objective: We compared the application accuracy of an infrared- based neuronavigation system when used with a novel automatic registration with its application accuracy when standard fiducial-based registration is performed. Methods: The automatic referencing tool is based on markers that are integrated in the headrest holder we routinely use in our intraoperative magnetic resonance imaging (MRI) setting and can be detected by the navigation software automatically. For navigation targeting we...

  1. Annual review in automatic programming

    CERN Document Server

    Goodman, Richard

    2014-01-01

    Annual Review in Automatic Programming, Volume 2 is a collection of papers that discusses the controversy about the suitability of COBOL as a common business oriented language, and the development of different common languages for scientific computation. A couple of papers describes the use of the Genie system in numerical calculation and analyzes Mercury autocode in terms of a phrase structure language, such as in the source language, target language, the order structure of ATLAS, and the meta-syntactical language of the assembly program. Other papers explain interference or an ""intermediate

  2. Receptor-Targeted Nipah Virus Glycoproteins Improve Cell-Type Selective Gene Delivery and Reveal a Preference for Membrane-Proximal Cell Attachment.

    Directory of Open Access Journals (Sweden)

    Ruben R Bender

    2016-06-01

    Full Text Available Receptor-targeted lentiviral vectors (LVs can be an effective tool for selective transfer of genes into distinct cell types of choice. Moreover, they can be used to determine the molecular properties that cell surface proteins must fulfill to act as receptors for viral glycoproteins. Here we show that LVs pseudotyped with receptor-targeted Nipah virus (NiV glycoproteins effectively enter into cells when they use cell surface proteins as receptors that bring them closely enough to the cell membrane (less than 100 Å distance. Then, they were flexible in receptor usage as demonstrated by successful targeting of EpCAM, CD20, and CD8, and as selective as LVs pseudotyped with receptor-targeted measles virus (MV glycoproteins, the current standard for cell-type specific gene delivery. Remarkably, NiV-LVs could be produced at up to two orders of magnitude higher titers compared to their MV-based counterparts and were at least 10,000-fold less effectively neutralized than MV glycoprotein pseudotyped LVs by pooled human intravenous immunoglobulin. An important finding for NiV-LVs targeted to Her2/neu was an about 100-fold higher gene transfer activity when particles were targeted to membrane-proximal regions as compared to particles binding to a more membrane-distal epitope. Likewise, the low gene transfer activity mediated by NiV-LV particles bound to the membrane distal domains of CD117 or the glutamate receptor subunit 4 (GluA4 was substantially enhanced by reducing receptor size to below 100 Å. Overall, the data suggest that the NiV glycoproteins are optimally suited for cell-type specific gene delivery with LVs and, in addition, for the first time define which parts of a cell surface protein should be targeted to achieve optimal gene transfer rates with receptor-targeted LVs.

  3. Broad target cell selectivity of Kaposi's sarcoma-associated herpesvirus glycoprotein-mediated cell fusion and virion entry

    International Nuclear Information System (INIS)

    The molecular mechanism of Kaposi's sarcoma-associated herpesvirus (KSHV, human herpesvirus 8) entry is poorly understood. We tested a broad variety of cell types of diverse species and tissue origin for their ability to function as targets in a quantitative reporter gene assay for KSHV-glycoprotein-mediated cell fusion. Several human, non-human primate, and rabbit cell lines were efficient targets, whereas rodent and all human lymphoblastoid cell lines were weak targets. Parallel findings were obtained with a virion entry assay using a recombinant KSHV encoding a reporter gene. No correlation was observed between target cell activity and surface expression of α3β1 integrin, a proposed KSHV receptor. We hypothesize that target cell permissiveness in both the cell fusion and virion entry assays reflects the presence of a putative KSHV fusion-entry receptor

  4. Recent advances in hopanoids analysis: Quantification protocols overview, main research targets and selected problems of complex data exploration.

    Science.gov (United States)

    Zarzycki, Paweł K; Portka, Joanna K

    2015-09-01

    Pentacyclic triterpenoids, particularly hopanoids, are organism-specific compounds and are generally considered as useful biomarkers that allow fingerprinting and classification of biological, environmental and geological samples. Simultaneous quantification of various hopanoids together with battery of related non-polar and low-molecular mass compounds may provide principal information for geochemical and environmental research focusing on both modern and ancient investigations. Target compounds can be derived from microbial biomass, water columns, sediments, coals, crude fossils or rocks. This create number of analytical problems due to different composition of the analytical matrix and interfering compounds and therefore, proper optimization of quantification protocols for such biomarkers is still the challenge. In this work we summarizing typical analytical protocols that were recently applied for quantification of hopanoids like compounds from different samples. Main steps including components of interest extraction, pre-purification, fractionation, derivatization and quantification involving gas (1D and 2D) as well as liquid separation techniques (liquid-liquid extraction, solid-phase extraction, planar and low resolution column chromatography, high-performance liquid chromatography) are described and discussed from practical point of view, mainly based on the experimental papers that were published within last two years, where significant increase in hopanoids research was noticed. The second aim of this review is to describe the latest research trends concerning determination of hopanoids and related low-molecular mass lipids analyzed in various samples including sediments, rocks, coals, crude oils and plant fossils as well as stromatolites and microbial biomass cultivated under different conditions. It has been found that majority of the most recent papers are based on uni- or bivariate approach for complex data analysis. Data interpretation involves

  5. Neuroanatomical automatic segmentation in brain cancer patients

    OpenAIRE

    D’Haese, P.; Niermann, K; Cmelak, A.; Donnelly, E.; Duay, V.; Li, R; Dawant, B.

    2003-01-01

    Conformally prescribed radiation therapy for brain cancer requires precisely defining the target treatment area, as well as delineating vital brain structures which must be spared from radiotoxicity. The current clinical practice of manually segmenting brain structures can be complex and exceedingly time consuming. Automatic computeraided segmentation methods have been proposed to increase efficiency and reproducibility in developing radiation treatment plans. Previous studies have establishe...

  6. Evaluation of Multiple Immunoassay Technology Platforms to Select the Anti-Drug Antibody Assay Exhibiting the Most Appropriate Drug and Target Tolerance

    Directory of Open Access Journals (Sweden)

    Justine Collet-Brose

    2016-01-01

    Full Text Available The aim of this study was, at the assay development stage and thus with an appropriate degree of rigor, to select the most appropriate technology platform and sample pretreatment procedure for a clinical ADA assay. Thus, ELISA, MSD, Gyrolab, and AlphaLISA immunoassay platforms were evaluated in association with target depletion and acid dissociation sample pretreatment steps. An acid dissociation step successfully improved the drug tolerance for all 4 technology platforms and the required drug tolerance was achieved with the Gyrolab and MSD platforms. The target tolerance was shown to be better for the ELISA format, where an acid dissociation treatment step alone was sufficient to achieve the desired target tolerance. However, inclusion of a target depletion step in conjunction with the acid treatment raised the target tolerance to the desired level for all of the technologies. A higher sensitivity was observed for the MSD and Gyrolab assays and the ELISA, MSD, and Gyrolab all displayed acceptable interdonor variability. This study highlights the usefulness of evaluating the performance of different assay platforms at an early stage in the assay development process to aid in the selection of the best fit-for-purpose technology platform and sample pretreatment steps.

  7. Evaluation of Multiple Immunoassay Technology Platforms to Select the Anti-Drug Antibody Assay Exhibiting the Most Appropriate Drug and Target Tolerance.

    Science.gov (United States)

    Collet-Brose, Justine; Couble, Pierre-Jean; Deehan, Maureen R; Nelson, Robert J; Ferlin, Walter G; Lory, Sabrina

    2016-01-01

    The aim of this study was, at the assay development stage and thus with an appropriate degree of rigor, to select the most appropriate technology platform and sample pretreatment procedure for a clinical ADA assay. Thus, ELISA, MSD, Gyrolab, and AlphaLISA immunoassay platforms were evaluated in association with target depletion and acid dissociation sample pretreatment steps. An acid dissociation step successfully improved the drug tolerance for all 4 technology platforms and the required drug tolerance was achieved with the Gyrolab and MSD platforms. The target tolerance was shown to be better for the ELISA format, where an acid dissociation treatment step alone was sufficient to achieve the desired target tolerance. However, inclusion of a target depletion step in conjunction with the acid treatment raised the target tolerance to the desired level for all of the technologies. A higher sensitivity was observed for the MSD and Gyrolab assays and the ELISA, MSD, and Gyrolab all displayed acceptable interdonor variability. This study highlights the usefulness of evaluating the performance of different assay platforms at an early stage in the assay development process to aid in the selection of the best fit-for-purpose technology platform and sample pretreatment steps. PMID:27243038

  8. Current management of farms and internal parasites by conventional and organic meat sheep French farmers and acceptance of targeted selective treatments.

    Science.gov (United States)

    Cabaret, J; Benoit, M; Laignel, G; Nicourt, C

    2009-09-16

    Sheep meat production in France is characterized by large flocks and a limited supply of labour. Digestive-tract strongyles are considered as one of the main health problems and control relies mostly on the use of anthelminthics, although resistance to at least the benzimidazoles is increasing. We conducted interviews on nine conventional and seven organic farms regarding whether an anthelmintic targeted selective treatment program could fit within the operations of the farms. In addition, necropsies of lambs were performed on three organic farms, and faecal egg counts and small lungworm counts were performed on all farms in autumn in ewes. Each interview consisted of an open discussion on sheep health and was terminated with comments on digestive-tract helminth infection as detected in parallel with the interview. Factors likely to affect the adoption of the targeted selective treatment approach were subjected to cluster analysis. Conventional farms were mostly advised by veterinarians and relied on systematic planning of anthelmintic treatments. The frequency of treatments was up to once a month for lambs and two to three times a year for ewes. The concept of selecting animals to be treated according to a scheme of targeted selective treatments based on phenotypic markers (e.g., anaemia, diarrhoea, weight gains) was not seen as feasible by these farmers. Conversely, organic farmers, with greater use of advisors and a restricted range of anthelmintic treatments were more susceptible to integrating phenotypic markers into their practices for controlling digestive-tract strongyles. PMID:19414221

  9. Limitations of Short Range Mexican Hat Connection for Driving Target Selection in a 2D Neural Field: Activity Suppression and Deviation from Input Stimuli.

    Directory of Open Access Journals (Sweden)

    Geoffrey eMégardon

    2015-10-01

    Full Text Available Dynamic Neural Field models (DNF often use a kernel of connection with short range excitation and long range inhibition. This organization has been suggested as a model for brain structures or for artificial systems involved in winner-take-all processes such as saliency localisation, perceptual decision or target/action selection. A good example of such a DNF is the superior colliculus (SC, a key structure for eye movements. Recent results suggest that the superficial layers of the SC (SCs exhibit relatively short range inhibition with a longer time constant than excitation. The aim of the present study was to further examine the properties of a DNF with such an inhibition pattern in the context of target selection. First we tested the effects of stimulus size and shape on when and where self-maintained clusters of firing neurons appeared, using three variants of the model. In each model variant, small stimuli led to rapid formation of a spiking cluster, a range of medium sizes led to the suppression of any activity on the network and hence to no target selection, while larger sizes led to delayed selection of multiple loci. Second, we tested the model with two stimuli separated by a varying distance. Again single, none, or multiple spiking clusters could occur, depending on distance and relative stimulus strength. For short distances, activity attracted towards the strongest stimulus, reminiscent of well-known behavioural data for saccadic eye movements, while for larger distances repulsion away from the second stimulus occurred. All these properties predicted by the model suggest that the SCs, or any other neural structure thought to implement a short range MH, is an imperfect winner-take-all system. Although those properties call for systematic testing, the discussion gathers neurophysiological and behavioural data suggesting that such properties are indeed present in target selection for saccadic eye movements.

  10. Empirical Evidence of Target Leverage, Adjustment Costs and Adjustment Speed of Non-Financial Firms in Selected African Countries

    OpenAIRE

    Oyebola Fatima Etudaiye-Muhtar; Rubi Ahmad

    2015-01-01

    The issue of target leverage for corporate firms in developing countries has received little attention in extant literature, especially countries in Africa. Given the imperfection that exists in African financial markets that may limit firms access to external capital, this study investigates dynamic adjustment towards a target debt ratio. In addition, the study used a dynamic panel data estimation technique to determine adjustment costs and speed of adjustment in non-financial firms in selec...

  11. Selective silencing of gene target expression by siRNA expression plasmids in human cervical cancer cells.

    Science.gov (United States)

    Peralta-Zaragoza, Oscar; De-la-O-Gómez, Faustino; Deas, Jessica; Fernández-Tilapa, Gloria; Fierros-Zárate, Geny Del Socorro; Gómez-Cerón, Claudia; Burguete-García, Ana; Torres-Poveda, Kirvis; Bermúdez-Morales, Victor Hugo; Rodríguez-Dorantes, Mauricio; Pérez-Plasencia, Carlos; Madrid-Marina, Vicente

    2015-01-01

    RNA interference is a natural mechanism to silence post-transcriptional gene expression in eukaryotic cells in which microRNAs act to cleave or halt the translation of target mRNAs at specific target sequences. Mature microRNAs, 19-25 nucleotides in length, mediate their effect at the mRNA level by inhibiting translation, or inducing cleavage of the mRNA target. This process is directed by the degree of complementary nucleotides between the microRNAs and the target mRNA; perfect complementary base pairing induces cleavage of mRNA, whereas several mismatches lead to translational arrest. Biological effects of microRNAs can be manipulated through the use of small interference RNAs (siRNAs) generated by chemical synthesis, or by cloning in molecular vectors. The cloning of a DNA insert in a molecular vector that will be transcribed into the corresponding siRNAs is an approach that has been developed using siRNA expression plasmids. These vectors contain DNA inserts designed with software to generate highly efficient siRNAs which will assemble into RNA-induced silencing complexes (RISC), and silence the target mRNA. In addition, the DNA inserts may be contained in cloning cassettes, and introduced in other molecular vectors. In this chapter we describe an attractive technology platform to silence cellular gene expression using specific siRNA expression plasmids, and evaluate its biological effect on target gene expression in human cervical cancer cells. PMID:25348304

  12. Automatic personnel selection for virtual team design

    OpenAIRE

    Kovačič, Matevž

    2009-01-01

    The following Master's thesis examines the concept of virtual teams, the need for virtual teams and how they are designed. An analysis of the functionality for human resource information system has been made and a data model has been projected. For a web portal has been used three-layer architecture. For the portal implementation advanced Microsoft technology has been used: ASP.NET 2.0, SQL Server 2005 database and other third-party software which contribute to a more efficient and standard p...

  13. Automatic Implantable Cardiac Defibrillator

    Medline Plus

    Full Text Available Automatic Implantable Cardiac Defibrillator February 19, 2009 Halifax Health Medical Center, Daytona Beach, FL Welcome to Halifax Health Daytona Beach, Florida. Over the next hour you' ...

  14. Automatic Payroll Deposit System.

    Science.gov (United States)

    Davidson, D. B.

    1979-01-01

    The Automatic Payroll Deposit System in Yakima, Washington's Public School District No. 7, directly transmits each employee's salary amount for each pay period to a bank or other financial institution. (Author/MLF)

  15. Rational design of point mutation-selective antisense DNA targeted to codon 12 of Ha-ras mRNA in human cells.

    Science.gov (United States)

    Duroux, I; Godard, G; Boidot-Forget, M; Schwab, G; Hélène, C; Saison-Behmoaras, T

    1995-09-11

    Antisense oligodeoxynucleotides targeted to Ha-ras mRNA have been designed to discriminate between the codon 12-mutated oncogene and the normal proto-oncogene. An in vitro assay using two different sources of RNase H (rabbit reticulocyte lysates and nuclear extract from HeLa cells) was used to characterize oligonucleotide binding to normal and mutated Ha-ras mRNA. Short oligonucleotides (12- or 13mers) centered on the mutation had a very high discriminatory efficiency. Longer oligonucleotides (16mers) did not discriminate efficiently between the mutated and the normal mRNA. We have tested the efficacy of dodecanucleotides to induce RNase H cleavage of the full-length mRNA, moving the target sequence from the loop to the stem region which is formed in the vicinity of mutated codon 12. The most selective oligonucleotides were centered on the mutation which is located near the junction between the loop and stem regions even though they were less efficient at inducing RNase H cleavage than those targeted to the loop region. The 12mer antisense oligonucleotide with the highest discriminatory power was selected for cell culture studies. This oligonucleotide inhibited the proliferation of a human cell line which had been transformed with the mutated Ha-ras gene (HBL100ras1) but had no effect on the parental cell line which was transfected with the vector DNA (HBL 100neo) and expressed only the normal Ha-ras gene. Growth inhibition of HBL100ras1 cells was associated with specific ablation of targeted Ha-ras mRNA as shown by RT-PCR. These results show that 'in vitro' evaluation using an RNase H assay allowed us to select an antisense oligonucleotide which elicited a selectivity towards point-mutated Ha-ras mRNA when added at 10 microM concentration to the culture medium of cells expressing wild type and mutated Ha-ras mRNA. PMID:7567450

  16. Automatic Arabic Text Classification

    OpenAIRE

    Al-harbi, S; Almuhareb, A.; Al-Thubaity , A; Khorsheed, M. S.; Al-Rajeh, A.

    2008-01-01

    Automated document classification is an important text mining task especially with the rapid growth of the number of online documents present in Arabic language. Text classification aims to automatically assign the text to a predefined category based on linguistic features. Such a process has different useful applications including, but not restricted to, e-mail spam detection, web page content filtering, and automatic message routing. This paper presents the results of experiments on documen...

  17. Automatic graphene transfer system for improved material quality and efficiency

    OpenAIRE

    Alberto Boscá; Jorge Pedrós; Javier Martínez; Tomás Palacios; Fernando Calle

    2015-01-01

    In most applications based on chemical vapor deposition (CVD) graphene, the transfer from the growth to the target substrate is a critical step for the final device performance. Manual procedures are time consuming and depend on handling skills, whereas existing automatic roll-to-roll methods work well for flexible substrates but tend to induce mechanical damage in rigid ones. A new system that automatically transfers CVD graphene to an arbitrary target substrate has been developed. The proce...

  18. Short Tandem Target Mimic: A Long Journey to the Engineered Molecular Landmine for Selective Destruction/Blockage of MicroRNAs in Plants and Animals

    Institute of Scientific and Technical Information of China (English)

    Guiliang Tang; Xiaoqing Tang

    2013-01-01

    MicroRNAs (miRNAs) are a population of highly conserved specific small ribo-regulators that negatively regulate gene expressions in both plants and animals.They play a key role in post-transcriptional gene regulation by destabilizing the target gene transcripts or blocking protein translation from them.Interestingly,these negative regulators are largely compromised by an upstream layer of negative regulators “target mimics” found in plants or “endogenous competing RNAs” revealed recently in animals.These endogenous regulatory mechanisms of “double negatives making a positive” have now been developed into a key strategy in the study of small RNA functions.This review presents some reflections on the long journey to the short tandem target mimic (STTM) for selective destruction/blockage of specific miRNAs in plants and animals,and the potential applications of STTM are discussed.

  19. Computer Corner: Automatic Differentiation and APL.

    Science.gov (United States)

    Neidinger, Richard D.

    1989-01-01

    Described are several programs that enable the user to evaluate derivatives to order n of any elementary function by using the combination of automatic differentiation method and A Programming Language (APL). Programs calculating first- and higher-order derivatives are presented. Selected APL symbols are appended. (YP)

  20. Experiments in Automatic Library of Congress Classification.

    Science.gov (United States)

    Larson, Ray R.

    1992-01-01

    Presents the results of research into the automatic selection of Library of Congress Classification numbers based on the titles and subject headings in MARC records from a test database at the University of California at Berkeley Library School library. Classification clustering and matching techniques are described. (44 references) (LRW)

  1. CRISPR-Mediated Drug-Target Validation Reveals Selective Pharmacological Inhibition of the RNA Helicase, eIF4A

    Directory of Open Access Journals (Sweden)

    Jennifer Chu

    2016-06-01

    Full Text Available Targeting translation initiation is an emerging anti-neoplastic strategy that capitalizes on de-regulated upstream MAPK and PI3K-mTOR signaling pathways in cancers. A key regulator of translation that controls ribosome recruitment flux is eukaryotic initiation factor (eIF 4F, a hetero-trimeric complex composed of the cap binding protein eIF4E, the scaffolding protein eIF4G, and the RNA helicase eIF4A. Small molecule inhibitors targeting eIF4F display promising anti-neoplastic activity in preclinical settings. Among these are some rocaglate family members that are well tolerated in vivo, deplete eIF4F of its eIF4A helicase subunit, have shown activity as single agents in several xenograft models, and can reverse acquired resistance to MAPK and PI3K-mTOR targeted therapies. Herein, we highlight the power of using genetic complementation approaches and CRISPR/Cas9-mediated editing for drug-target validation ex vivo and in vivo, linking the anti-tumor properties of rocaglates to eIF4A inhibition.

  2. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered plants on non-target organisms

    Science.gov (United States)

    Most regulatory authorities require that developers of genetically engineered insect-resistant (GEIR) crops evaluate the potential for these crops to have adverse impacts on valued non-target organisms (NTOs), i.e., organisms not intended to be controlled by the trait. In many cases, impacts to NTOs...

  3. Screening closing scenarios for tactical targets

    Science.gov (United States)

    Sefcik, Jason A.; Lee, Harry C.; Olson, Teresa L. P.

    2002-07-01

    The first step in an automatic image target acquisition system is determining the location of candidate objects. Screening for targets must also be done within a tactical scenario timeframe. The screening process must only require a portion of the processing workload since other algorithms must execute in the same time frame. The detection of these candidate objects is allocated to two functions within the same algorithm. The first is a pre-screener and other is a clutter rejection component that will categorize the object nomination into target or non-target classes. This paper describes a screener that meets the necessary requirements for tactical operations. It uses the magnitude and direction of the image gradient. Locations are nominated by looking at local neighborhoods in this gradient space. Regions of interest are then selected and various features are extracted. These features are selected both for their information content and their ease of calculation. Using a Bayes approach, target candidates are selected as plausible targets of interest.

  4. A DVH-guided IMRT optimization algorithm for automatic treatment planning and adaptive radiotherapy replanning

    Energy Technology Data Exchange (ETDEWEB)

    Zarepisheh, Masoud; Li, Nan [Department of Radiation Medicine and Applied Sciences and Center for Advanced Radiotherapy Technologies, University of California San Diego, La Jolla, California 92037-0843 (United States); Long, Troy; Romeijn, H. Edwin [Department of Industrial and Operations Engineering, University of Michigan, Ann Arbor, Michigan 48109-2117 (United States); Tian, Zhen; Jia, Xun; Jiang, Steve B., E-mail: Steve.Jiang@UTSouthwestern.edu [Department of Radiation Medicine and Applied Sciences and Center for Advanced Radiotherapy Technologies, University of California San Diego, La Jolla, California 92037-0843 and Department of Radiation Oncology, University of Texas Southwestern Medical Center, Dallas, Texas 75390-8542 (United States)

    2014-06-15

    Purpose: To develop a novel algorithm that incorporates prior treatment knowledge into intensity modulated radiation therapy optimization to facilitate automatic treatment planning and adaptive radiotherapy (ART) replanning. Methods: The algorithm automatically creates a treatment plan guided by the DVH curves of a reference plan that contains information on the clinician-approved dose-volume trade-offs among different targets/organs and among different portions of a DVH curve for an organ. In ART, the reference plan is the initial plan for the same patient, while for automatic treatment planning the reference plan is selected from a library of clinically approved and delivered plans of previously treated patients with similar medical conditions and geometry. The proposed algorithm employs a voxel-based optimization model and navigates the large voxel-based Pareto surface. The voxel weights are iteratively adjusted to approach a plan that is similar to the reference plan in terms of the DVHs. If the reference plan is feasible but not Pareto optimal, the algorithm generates a Pareto optimal plan with the DVHs better than the reference ones. If the reference plan is too restricting for the new geometry, the algorithm generates a Pareto plan with DVHs close to the reference ones. In both cases, the new plans have similar DVH trade-offs as the reference plans. Results: The algorithm was tested using three patient cases and found to be able to automatically adjust the voxel-weighting factors in order to generate a Pareto plan with similar DVH trade-offs as the reference plan. The algorithm has also been implemented on a GPU for high efficiency. Conclusions: A novel prior-knowledge-based optimization algorithm has been developed that automatically adjust the voxel weights and generate a clinical optimal plan at high efficiency. It is found that the new algorithm can significantly improve the plan quality and planning efficiency in ART replanning and automatic treatment

  5. A DVH-guided IMRT optimization algorithm for automatic treatment planning and adaptive radiotherapy replanning

    International Nuclear Information System (INIS)

    Purpose: To develop a novel algorithm that incorporates prior treatment knowledge into intensity modulated radiation therapy optimization to facilitate automatic treatment planning and adaptive radiotherapy (ART) replanning. Methods: The algorithm automatically creates a treatment plan guided by the DVH curves of a reference plan that contains information on the clinician-approved dose-volume trade-offs among different targets/organs and among different portions of a DVH curve for an organ. In ART, the reference plan is the initial plan for the same patient, while for automatic treatment planning the reference plan is selected from a library of clinically approved and delivered plans of previously treated patients with similar medical conditions and geometry. The proposed algorithm employs a voxel-based optimization model and navigates the large voxel-based Pareto surface. The voxel weights are iteratively adjusted to approach a plan that is similar to the reference plan in terms of the DVHs. If the reference plan is feasible but not Pareto optimal, the algorithm generates a Pareto optimal plan with the DVHs better than the reference ones. If the reference plan is too restricting for the new geometry, the algorithm generates a Pareto plan with DVHs close to the reference ones. In both cases, the new plans have similar DVH trade-offs as the reference plans. Results: The algorithm was tested using three patient cases and found to be able to automatically adjust the voxel-weighting factors in order to generate a Pareto plan with similar DVH trade-offs as the reference plan. The algorithm has also been implemented on a GPU for high efficiency. Conclusions: A novel prior-knowledge-based optimization algorithm has been developed that automatically adjust the voxel weights and generate a clinical optimal plan at high efficiency. It is found that the new algorithm can significantly improve the plan quality and planning efficiency in ART replanning and automatic treatment

  6. DNA target selectivity by the vitamin D3 receptor: mechanism of dimer binding to an asymmetric repeat element.

    OpenAIRE

    Towers, T L; Luisi, B F; Asianov, A; Freedman, L P

    1993-01-01

    The 1,25-dihydroxyvitamin D3 receptor, like other members of the nuclear receptor superfamily, forms dimers in solution that are probably stabilized by a dyad symmetrical interface formed by the ligand-binding domain. This receptor, however, recognizes DNA targets that are not dyad symmetric but rather are organized as direct repeats of a hexameric sequence with a characteristic 3-bp spacing. Using molecular modeling and site-directed mutagenesis, we have identified regions within the vitamin...

  7. SDSS-III Baryon Oscillation Spectroscopic Survey Data Release 12:galaxy target selection and large scale structure catalogues

    OpenAIRE

    Reid, Beth; Ho, Shirley; Padmanabhan, Nikhil; Percival, Will J.; Tinker, Jeremy; Tojeiro, Rita; White, Martin; Eisenstein, Daniel J.; Maraston, Claudia; Ross, Ashley J.; Sanchez, Ariel G.; Schlegel, David; Sheldon, Erin; Strauss, Michael A.; Thomas, Daniel

    2016-01-01

    The Baryon Oscillation Spectroscopic Survey (BOSS), part of the Sloan Digital Sky Survey (SDSS) III project, has provided the largest survey of galaxy redshifts available to date, in terms of both the number of galaxy redshifts measured by a single survey, and the effective cosmological volume covered. Key to analysing the clustering of these data to provide cosmological measurements is understanding the detailed properties of this sample. Potential issues include variations in the target cat...

  8. SOMATOSTATIN RECEPTOR SUBTYPE 2A IMMUNOHISTOCHEMISTRY USING A NEW MONOCLONAL ANTIBODY SELECTS TUMORS SUITABLE FOR IN VIVO SOMATOSTATIN RECEPTOR TARGETING

    OpenAIRE

    Körner, Meike; Waser, Beatrice; Schonbrunn, Agnes; Perren, Aurel; Reubi, Jean Claude

    2012-01-01

    High over-expression of somatostatin receptors in neuroendocrine tumors allows imaging and radiotherapy with radiolabelled somatostatin analogues. To know if a tumor is suitable for in vivo somatostatin receptor targeting, its somatostatin receptor expression has to be determined. There are specific indications to use immunohistochemistry for the somatostatin receptor subtype 2A (sst2A), but this has up to now been limited by the lack of an adequate reliable antibody. The aim of the present s...

  9. Automatic Program Development

    DEFF Research Database (Denmark)

    Automatic Program Development is a tribute to Robert Paige (1947-1999), our accomplished and respected colleague, and moreover our good friend, whose untimely passing was a loss to our academic and research community. We have collected the revised, updated versions of the papers published in his...... honor in the Higher-Order and Symbolic Computation Journal in the years 2003 and 2005. Among them there are two papers by Bob: (i) a retrospective view of his research lines, and (ii) a proposal for future studies in the area of the automatic program derivation. The book also includes some papers by...... members of the IFIP Working Group 2.1 of which Bob was an active member. All papers are related to some of the research interests of Bob and, in particular, to the transformational development of programs and their algorithmic derivation from formal specifications. Automatic Program Development offers a...

  10. Automatic utilities auditing

    Energy Technology Data Exchange (ETDEWEB)

    Smith, Colin Boughton [Energy Metering Technology (United Kingdom)

    2000-08-01

    At present, energy audits represent only snapshot situations of the flow of energy. The normal pattern of energy audits as seen through the eyes of an experienced energy auditor is described. A brief history of energy auditing is given. It is claimed that the future of energy auditing lies in automatic meter reading with expert data analysis providing continuous automatic auditing thereby reducing the skill element. Ultimately, it will be feasible to carry out auditing at intervals of say 30 minutes rather than five years.

  11. Automatic Camera Control

    DEFF Research Database (Denmark)

    Burelli, Paolo; Preuss, Mike

    2014-01-01

    Automatically generating computer animations is a challenging and complex problem with applications in games and film production. In this paper, we investigate howto translate a shot list for a virtual scene into a series of virtual camera configurations — i.e automatically controlling the virtual...... camera. We approach this problem by modelling it as a dynamic multi-objective optimisation problem and show how this metaphor allows a much richer expressiveness than a classical single objective approach. Finally, we showcase the application of a multi-objective evolutionary algorithm to generate a shot...

  12. Automatic text summarization

    CERN Document Server

    Torres Moreno, Juan Manuel

    2014-01-01

    This new textbook examines the motivations and the different algorithms for automatic document summarization (ADS). We performed a recent state of the art. The book shows the main problems of ADS, difficulties and the solutions provided by the community. It presents recent advances in ADS, as well as current applications and trends. The approaches are statistical, linguistic and symbolic. Several exemples are included in order to clarify the theoretical concepts.  The books currently available in the area of Automatic Document Summarization are not recent. Powerful algorithms have been develop

  13. Metallogenic geologic prerequisites of sandstone-type uranium deposits and target area selection. Taking Erlian and Ordos basins as examples

    International Nuclear Information System (INIS)

    Sandstone-type uranium deposit is the main target of recent uranium prospecting and exploration. According to the metallogenic characteristics, sandstone-type uranium deposits are divided into three groups: paleo-channel type, interlayer oxidation zone type and phreatic interlayer oxidation type. The author makes an analysis on the geologic prerequisites of the three types of uranium deposits, the similarities and difference, and preliminarily summarizes genetic models of different types of uranium deposits. Finally, taking Erlian and Ordos basins as examples, the author makes an evaluation and a strategic analysis on the uranium metallogenic prospect of the above two basins

  14. Selective Life-Long Skeletal Myofiber-Targeted VEGF Gene Ablation Impairs Exercise Capacity in Adult Mice.

    Science.gov (United States)

    Tang, Kechun; Gu, Yusu; Dalton, Nancy D; Wagner, Harrieth; Peterson, Kirk L; Wagner, Peter D; Breen, Ellen C

    2016-02-01

    Exercise is dependent on adequate oxygen supply for mitochondrial respiration in both cardiac and locomotor muscle. To determine whether skeletal myofiber VEGF is critical for regulating exercise capacity, independent of VEGF function in the heart, ablation of the VEGF gene was targeted to skeletal myofibers (skmVEGF-/-) during embryogenesis (∼ E9.5), leaving intact VEGF expression by all other cells in muscle. In adult mice, VEGF levels were decreased in the soleus (by 65%), plantaris (94%), gastrocnemius (74%), EDL (99%) and diaphragm (64%) (P exercise capacity. PMID:26201683

  15. What parameters to consider and which software tools to use for target selection and molecular design of small interfering RNAs.

    Science.gov (United States)

    Matveeva, Olga

    2013-01-01

    The design of small gene silencing RNAs with a high probability of being efficient still has some elements of an art, especially when the lowest concentration of small molecules needs to be utilized. The design of highly target-specific small interfering RNAs or short hairpin RNAs is even a greater challenging task. Some logical schemes and software tools that can be used for simplifying both tasks are presented here. In addition, sequence motifs and sequence composition biases of small interfering RNAs that have to be avoided because of specificity concerns are also detailed. PMID:23027043

  16. Discovery of selective inhibitors of tyrosyl-DNA phosphodiesterase 2 by targeting the enzyme DNA-binding cleft.

    Science.gov (United States)

    Kossmann, Bradley R; Abdelmalak, Monica; Lopez, Sophia; Tender, Gabrielle; Yan, Chunli; Pommier, Yves; Marchand, Christophe; Ivanov, Ivaylo

    2016-07-15

    Tyrosyl-DNA phosphodiesterase 2 (TDP2) processes protein/DNA adducts resulting from abortive DNA topoisomerase II (Top2) activity. TDP2 inhibition could provide synergism with the Top2 poison class of chemotherapeutics. By virtual screening of the NCI diversity small molecule database, we identified selective TDP2 inhibitors and experimentally verified their selective inhibitory activity. Three inhibitors exhibited low-micromolar IC50 values. Molecular dynamics simulations revealed a common binding mode for these inhibitors, involving association to the TDP2 DNA-binding cleft. MM-PBSA per-residue energy decomposition identified important interactions of the compounds with specific TDP2 residues. These interactions could provide new avenues for synthetic optimization of these scaffolds. PMID:27262595

  17. AUTOMATIC WEB SCRAPPING USING VISUAL SELECTORS

    Directory of Open Access Journals (Sweden)

    Rashmi Bhosale

    2015-12-01

    Full Text Available The amount of information that is currently vailable on the net grows at a very fast pace, thus web can be considered as the largest knowledge repository ever developed and made available to the public. A web data extraction system is a system that extracts data from web pages automatically. Web data analysis applications such as extracting mutual funds information from a website, extracting opening and closing price of stock daily from a web page and so on involves web data extraction.Early techniques were construcingt wrapper to visit those sites and collect data which is time consuming. Thus a technique called as Automatic Web Scrapping Using Visual Selectors(AWSUVS is proposed. For selected data sections AWSUVS discovers extraction pattern automatically. AWSUVS uses visual cues to identify data records while ignoring noise items such as advertises and navigation bars.

  18. Research on an Intelligent Automatic Turning System

    Directory of Open Access Journals (Sweden)

    Lichong Huang

    2012-12-01

    Full Text Available Equipment manufacturing industry is the strategic industries of a country. And its core part is the CNC machine tool. Therefore, enhancing the independent research of relevant technology of CNC machine, especially the open CNC system, is of great significance. This paper presented some key techniques of an Intelligent Automatic Turning System and gave a viable solution for system integration. First of all, the integrated system architecture and the flexible and efficient workflow for perfoming the intelligent automatic turning process is illustrated. Secondly, the innovated methods of the workpiece feature recognition and expression and process planning of the NC machining are put forward. Thirdly, the cutting tool auto-selection and the cutting parameter optimization solution are generated with a integrated inference of rule-based reasoning and case-based reasoning. Finally, the actual machining case based on the developed intelligent automatic turning system proved the presented solutions are valid, practical and efficient.

  19. Automatic inference of indexing rules for MEDLINE

    Directory of Open Access Journals (Sweden)

    Shooshan Sonya E

    2008-11-01

    Full Text Available Abstract Background: Indexing is a crucial step in any information retrieval system. In MEDLINE, a widely used database of the biomedical literature, the indexing process involves the selection of Medical Subject Headings in order to describe the subject matter of articles. The need for automatic tools to assist MEDLINE indexers in this task is growing with the increasing number of publications being added to MEDLINE. Methods: In this paper, we describe the use and the customization of Inductive Logic Programming (ILP to infer indexing rules that may be used to produce automatic indexing recommendations for MEDLINE indexers. Results: Our results show that this original ILP-based approach outperforms manual rules when they exist. In addition, the use of ILP rules also improves the overall performance of the Medical Text Indexer (MTI, a system producing automatic indexing recommendations for MEDLINE. Conclusion: We expect the sets of ILP rules obtained in this experiment to be integrated into MTI.

  20. Identification and characterization of alphavirus M1 as a selective oncolytic virus targeting ZAP-defective human cancers

    OpenAIRE

    Lin, Yuan; Zhang, Haipeng; Liang, Jiankai; Kai LI; Zhu, Wenbo; FU, LIWU; Wang, Fang; Zheng, Xiaoke; Shi, Huijuan; Wu, Sihan; Xiao, Xiao; Chen, Lijun; TANG, LIPENG; Yan, Min; Yang, Xiaoxiao

    2014-01-01

    Although oncolytic virotherapy is showing great promise in clinical trials, not all patients are benefiting. Identifying predictors of therapeutic effectiveness for each oncolytic virus would provide a good chance to increase response rate. Here, we describe an alphavirus (M1) that possesses selective and potent antitumor activity through intravenous infusion, whereas its replication is controlled by the zinc-finger antiviral protein (ZAP) gene. A survey of cancer tissue banks reveals that ZA...

  1. Small and dim target detection via lateral inhibition filtering and Artificial Bee colony based selective visual attention.

    Science.gov (United States)

    Duan, Haibin; Deng, Yimin; Wang, Xiaohua; Xu, Chunfang

    2013-01-01

    This paper proposed a novel bionic selective visual attention mechanism to quickly select regions that contain salient objects to reduce calculations. Firstly, lateral inhibition filtering, inspired by the limulus' ommateum, is applied to filter low-frequency noises. After the filtering operation, we use Artificial Bee Colony (ABC) algorithm based selective visual attention mechanism to obtain the interested object to carry through the following recognition operation. In order to eliminate the camera motion influence, this paper adopted ABC algorithm, a new optimization method inspired by swarm intelligence, to calculate the motion salience map to integrate with conventional visual attention. To prove the feasibility and effectiveness of our method, several experiments were conducted. First the filtering results of lateral inhibition filter were shown to illustrate its noise reducing effect, then we applied the ABC algorithm to obtain the motion features of the image sequence. The ABC algorithm is proved to be more robust and effective through the comparison between ABC algorithm and popular Particle Swarm Optimization (PSO) algorithm. Except for the above results, we also compared the classic visual attention mechanism and our ABC algorithm based visual attention mechanism, and the experimental results of which further verified the effectiveness of our method. PMID:23991033

  2. Genetic identification of thiosulfate sulfurtransferase as an adipocyte-expressed antidiabetic target in mice selected for leanness.

    Science.gov (United States)

    Morton, Nicholas M; Beltram, Jasmina; Carter, Roderick N; Michailidou, Zoi; Gorjanc, Gregor; McFadden, Clare; Barrios-Llerena, Martin E; Rodriguez-Cuenca, Sergio; Gibbins, Matthew T G; Aird, Rhona E; Moreno-Navarrete, José Maria; Munger, Steven C; Svenson, Karen L; Gastaldello, Annalisa; Ramage, Lynne; Naredo, Gregorio; Zeyda, Maximilian; Wang, Zhao V; Howie, Alexander F; Saari, Aila; Sipilä, Petra; Stulnig, Thomas M; Gudnason, Vilmundur; Kenyon, Christopher J; Seckl, Jonathan R; Walker, Brian R; Webster, Scott P; Dunbar, Donald R; Churchill, Gary A; Vidal-Puig, Antonio; Fernandez-Real, José Manuel; Emilsson, Valur; Horvat, Simon

    2016-07-01

    The discovery of genetic mechanisms for resistance to obesity and diabetes may illuminate new therapeutic strategies for the treatment of this global health challenge. We used the polygenic 'lean' mouse model, which has been selected for low adiposity over 60 generations, to identify mitochondrial thiosulfate sulfurtransferase (Tst; also known as rhodanese) as a candidate obesity-resistance gene with selectively increased expression in adipocytes. Elevated adipose Tst expression correlated with indices of metabolic health across diverse mouse strains. Transgenic overexpression of Tst in adipocytes protected mice from diet-induced obesity and insulin-resistant diabetes. Tst-deficient mice showed markedly exacerbated diabetes, whereas pharmacological activation of TST ameliorated diabetes in mice. Mechanistically, TST selectively augmented mitochondrial function combined with degradation of reactive oxygen species and sulfide. In humans, TST mRNA expression in adipose tissue correlated positively with insulin sensitivity in adipose tissue and negatively with fat mass. Thus, the genetic identification of Tst as a beneficial regulator of adipocyte mitochondrial function may have therapeutic significance for individuals with type 2 diabetes. PMID:27270587

  3. A survey of luminous high-redshift quasars with SDSS and WISE. I. target selection and optical spectroscopy

    CERN Document Server

    Wang, Feige; Fan, Xiaohui; Yang, Jinyi; Yi, Weimin; Bian, Fuyan; McGreer, Ian D; Yang, Qian; Ai, Yanli; Dong, Xiaoyi; Zuo, Wenwen; Jiang, Linhua; Green, Richard; Wang, Shu; Cai, Zheng; Wang, Ran; Yue, Minghao

    2016-01-01

    High-redshift quasars are important tracers of structure and evolution in the early universe. However, they are very rare and difficult to find when using color selection because of contamination from late-type dwarfs. High-redshift quasar surveys based on only optical colors suffer from incompleteness and low identification efficiency, especially at $z\\gtrsim4.5$. We have developed a new method to select $4.7\\lesssim z \\lesssim 5.4$ quasars with both high efficiency and completeness by combining optical and mid-IR Wide-field Infrared Survey Explorer (WISE) photometric data, and are conducting a luminous $z\\sim5$ quasar survey in the whole Sloan Digital Sky Survey (SDSS) footprint. We have spectroscopically observed 99 out of 110 candidates with $z$-band magnitudes brighter than 19.5 and 64 (64.6\\%) of them are quasars with redshifts of $4.4\\lesssim z \\lesssim 5.5$ and absolute magnitudes of $-29\\lesssim M_{1450} \\lesssim -26.4$. In addition, we also observed 14 fainter candidates selected with the same crite...

  4. Special hydrogen target (Prop. 210)

    International Nuclear Information System (INIS)

    This guide contains a description of the electrical control and automatic vacuum systems for the Special Hydrogen Target (Prop. 210) together with the flow diagram and the mimic control panel layout for the system. (U.K.)

  5. Automatic Dance Lesson Generation

    Science.gov (United States)

    Yang, Yang; Leung, H.; Yue, Lihua; Deng, LiQun

    2012-01-01

    In this paper, an automatic lesson generation system is presented which is suitable in a learning-by-mimicking scenario where the learning objects can be represented as multiattribute time series data. The dance is used as an example in this paper to illustrate the idea. Given a dance motion sequence as the input, the proposed lesson generation…

  6. Automatic Complexity Analysis

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    1989-01-01

    One way to analyse programs is to to derive expressions for their computational behaviour. A time bound function (or worst-case complexity) gives an upper bound for the computation time as a function of the size of input. We describe a system to derive such time bounds automatically using abstract...

  7. Structure and selectivity of novel ω-conotoxins and conus catus that target neuronal calcium channel subtypes

    International Nuclear Information System (INIS)

    Full text: ω-Conotoxins selective for N-type voltage-sensitive calcium channels have promising therapeutic applications in conditions such as pain and neurodegeneration following cerebral ischaemia. Here we report the discovery of novel conotoxins from the piscivorous snail Conus carus using 125I-GVIA binding to rat brain membrane to guide fractionation of crude venom, and cloning to identify the expressed gene products from the venom duct tissue. Four peptides were isolated and named ω-conotoxins CVIA-D (CVIA-D) on the basis of their pharmacology and structure. CVIA-D had varying extents of homology to other ω-conotoxins, with loop 4 of CVID showing significant sequence divergence. From binding studies in rat brain, the rank order of potency to displace 125I-GVIA from N-type calcium channel (CVID = GVIA=MVIIA > CVIA > CVIC = CVIB > MVIIC) was reversed at the P/Q-type calcium channel (defined by 125I-MVIIC). CVID was most selective for N-type vs P/Q-type calcium channels, being 1.5 to 2-orders of magnitude more selective than GVIA and MVIIA, respectively. CVIA-D each inhibited neurally-evoked contractions in rat vas deferens in a reversible manner, with potencies that correlated with their ability to inhibit 125I-GVIA binding. Compared with GVIA, CVID was a more potent inhibitor of central N-type calcium channels (α1,B-dexpressed in Xenopus oocytes) than of peripheral N-type calcium channels (rat vas deferens). 1H NMR studies revealed that CVID adopts a similar 3D fold to other ω-conotoxins. However, in contrast to GVIA, MVIIA or MVIIC, CVID has two hydrogen bonds that hold loops 2 and 4 proximal, a factor that may contribute to the enhanced ability of CVID to discriminate among neuronal calcium channels

  8. Selective Serotonin Reuptake Inhibitor Fluoxetine Inhibits Replication of Human Enteroviruses B and D by Targeting Viral Protein 2C

    OpenAIRE

    Ulferts, R.; van der Linden, L.; Thibaut, H.J.; Lanke, K. H. W.; Leyssen, P.; Coutard, B.; De Palma, A.M.; Canard, B; Neyts, J.; Van Kuppeveld, F. J. M.

    2013-01-01

    Although the genus Enterovirus contains many important human pathogens, there is no licensed drug for either the treatment or the prophylaxis of enterovirus infections. We report that fluoxetine (Prozac)-a selective serotonin reuptake inhibitor-inhibits the replication of human enterovirus B (HEV-B) and HEV-D but does not affect the replication of HEV-A and HEV-C or human rhinovirus A or B. We show that fluoxetine interferes with viral RNA replication, and we identified viral protein 2C as th...

  9. Zea mays(L.) P1 locus for cob glume color identified as a post-domestication selection target with an effect on temperate maize genomes

    Institute of Scientific and Technical Information of China (English)

    Chuanxiao; Xie; Jianfeng; Weng; Wenguo; Liu; Cheng; Zou; Zhuanfang; Hao; Wenxue; Li; Minshun; Li; Xiaosen; Guo; Gengyun; Zhang; Yunbi; Xu; Xinhai; Li; Shihuang; Zhang

    2013-01-01

    Artificial selection during domestication and post-domestication improvement results in loss of genetic diversity near target loci. However, the genetic locus associated with cob glume color and the nature of the genomic pattern surrounding it was elusive and the selection effect in that region was not clear. An association mapping panel consisting of 283 diverse modern temperate maize elite lines was genotyped by a chip containing over 55,000 evenly distributed SNPs. Ten-fold resequencing at the target region on 40 of the panel lines and 47 tropical lines was also undertaken. A genome-wide association study(GWAS) for cob glume color confirmed the P1 locus, which is located on the short arm of chromosome 1, with a-log10 P value for surrounding SNPs higher than the Bonferroni threshold(α/n, α < 0.001) when a mixed linear model(MLM) was implemented. A total of 26 markers were identified in a 0.78 Mb region surrounding the P1 locus, including 0.73 Mb and 0.05 Mb upstream and downstream of the P1 gene, respectively. A clear linkage disequilibrium(LD) block was found and LD decayed very rapidly with increasing physical distance surrounding the P1 locus. The estimates of π and Tajima’s D were significantly(P < 0.001) lower at both ends compared to the locus. Upon comparison of temperate and tropical lines at much finer resolution by resequencing(180-fold finer than chip SNPs), a more structured LD block pattern was found among the 40 resequenced temperate lines. All evidence indicates that the P1 locus in temperate maize has not undergone neutral evolution but has been subjected to artificial selection during post-domestication selection or improvement. The information and analytical results generated in this study provide insights as to how breeding efforts have affected genome evolution in crop plants.

  10. Practical consideration in the selection of X-ray fluorescence tube targets for analysis of geological materials

    International Nuclear Information System (INIS)

    Four X-ray fluorescence tubes with different targets (Cr, W, Mo and Rh) were compared for their suitability to analyze twelve of the most common major and trace elements in some geological samples. The major elements and Si, Al, Ca, K, Ti, and S. All elements having wavelengths higher than that of the iron K-absorption edge, gave significantly higher intensities of their characteristic fluorescence radiations when using a Cr-anode tube compared to W, Mo and Rh anode tubes. However, for the light elements (Si and Al) the Rh-anode tube of equal efficiency as the Cr-anode tube. The highest Ka-line intensity of Fe was obtained by the W-anode tube. The lowest detection limits (highest sensitivity) for the trace elements Rb, Sr, Zr, and Nb are obtained using both the Mo and Rh tubes. (author)

  11. Targeting of VX2 Rabbit Liver Tumor by Selective Delivery of 3-Bromopyruvate: A Biodistribution and Survival Study

    OpenAIRE

    Vali, Mustafa; Vossen, Josephina A.; Buijs, Manon; Engles, James M; Liapi, Eleni; Ventura, Veronica Prieto; Khwaja, Afsheen; Acha-Ngwodo, Obele; Shanmugasundaram, Ganapathy; Syed, Labiq; Wahl, Richard L.; Geschwind, Jean-Francois H

    2008-01-01

    The aim of this study was to determine the biodistribution and tumor targeting ability of 14C-labeled 3-bromopyruvate ([14C]3-BrPA) after i.a. and i.v. delivery in the VX2 rabbit model. In addition, we evaluated the effects of [14C]3-BrPA on tumor and healthy tissue glucose metabolism by determining 18F-deoxyglucose (FDG) uptake. Last, we determined the survival benefit of i.a. administered 3-BrPA. In total, 60 rabbits with VX2 liver tumor received either 1.75 mM [14C]3-BrPA i.a., 1.75 mM [14...

  12. Differential Expression of FosB Proteins and Potential Target Genes in Select Brain Regions of Addiction and Depression Patients.

    Science.gov (United States)

    Gajewski, Paula A; Turecki, Gustavo; Robison, Alfred J

    2016-01-01

    Chronic exposure to stress or drugs of abuse has been linked to altered gene expression throughout the body, and changes in gene expression in discrete brain regions are thought to underlie many psychiatric diseases, including major depressive disorder and drug addiction. Preclinical models of these disorders have provided evidence for mechanisms of this altered gene expression, including transcription factors, but evidence supporting a role for these factors in human patients has been slow to emerge. The transcription factor ΔFosB is induced in the prefrontal cortex (PFC) and hippocampus (HPC) of rodents in response to stress or cocaine, and its expression in these regions is thought to regulate their "top down" control of reward circuitry, including the nucleus accumbens (NAc). Here, we use biochemistry to examine the expression of the FosB family of transcription factors and their potential gene targets in PFC and HPC postmortem samples from depressed patients and cocaine addicts. We demonstrate that ΔFosB and other FosB isoforms are downregulated in the HPC but not the PFC in the brains of both depressed and addicted individuals. Further, we show that potential ΔFosB transcriptional targets, including GluA2, are also downregulated in the HPC but not PFC of cocaine addicts. Thus, we provide the first evidence of FosB gene expression in human HPC and PFC in these psychiatric disorders, and in light of recent findings demonstrating the critical role of HPC ΔFosB in rodent models of learning and memory, these data suggest that reduced ΔFosB in HPC could potentially underlie cognitive deficits accompanying chronic cocaine abuse or depression. PMID:27494187

  13. Automatic detection of abnormalities in mammograms

    OpenAIRE

    Suhail, Zobia; Sarwar, Mansoor; Murtaza, Kashif

    2015-01-01

    Background In recent years, an increased interest has been seen in the area of medical image processing and, as a consequence, Computer Aided Diagnostic (CAD) systems. The basic purpose of CAD systems is to assist doctors in the process of diagnosis. CAD systems, however, are quite expensive, especially, in most of the developing countries. Our focus is on developing a low-cost CAD system. Today, most of the CAD systems regarding mammogram classification target automatic detection of calcific...

  14. Error Rates in Users of Automatic Face Recognition Software.

    Directory of Open Access Journals (Sweden)

    David White

    Full Text Available In recent years, wide deployment of automatic face recognition systems has been accompanied by substantial gains in algorithm performance. However, benchmarking tests designed to evaluate these systems do not account for the errors of human operators, who are often an integral part of face recognition solutions in forensic and security settings. This causes a mismatch between evaluation tests and operational accuracy. We address this by measuring user performance in a face recognition system used to screen passport applications for identity fraud. Experiment 1 measured target detection accuracy in algorithm-generated 'candidate lists' selected from a large database of passport images. Accuracy was notably poorer than in previous studies of unfamiliar face matching: participants made over 50% errors for adult target faces, and over 60% when matching images of children. Experiment 2 then compared performance of student participants to trained passport officers-who use the system in their daily work-and found equivalent performance in these groups. Encouragingly, a group of highly trained and experienced "facial examiners" outperformed these groups by 20 percentage points. We conclude that human performance curtails accuracy of face recognition systems-potentially reducing benchmark estimates by 50% in operational settings. Mere practise does not attenuate these limits, but superior performance of trained examiners suggests that recruitment and selection of human operators, in combination with effective training and mentorship, can improve the operational accuracy of face recognition systems.

  15. 联合互信息水下目标特征选择算法%Joint Mutual Information Feature Selection for Underwater Acoustic Targets

    Institute of Scientific and Technical Information of China (English)

    申昇; 杨宏晖; 王芸; 潘悦; 唐建生

    2015-01-01

    The existing exhaustive feature selection algorithms can select the optimal feature subset of an underwater acoustic target but cannot be used in engineering practices because of their too high computational cost. To balance the computational cost and the optimal feature subset search, we propose what we believe to be a new joint mutual information feature selection (JMIFS) algorithm. Its core consists of: we use the sequence forward feature search mechanism to select the feature that shows the largest amount of mutual information for classification and then select the feature that contributes more mutual information that is complementary to the selected feature so as to remove the noise and redundant features of the underwater acoustic target and enhance the recognition performance. We simu⁃late the selection of multi⁃field features of four classes of underwater acoustic targets. The simulation results show preliminarily that: on the condition that the recognition accuracy of the SVM classifier declines only 1%, our JMIFS algorithm can reduce about 87% of the redundant features, and its classification time decreases by 58%. Compared with the SVM and genetic algorithm hybrid feature selection algorithms, the JMIFS algorithm selects a smaller num⁃ber of feature subsets that have a better generalization performance.%在特征选择算法中,穷举特征选择算法可选择出最优特征子集,但由于计算量过高而在实际中不可实现。针对计算成本和最优特征子集搜索之间的平衡问题,提出一种新的用于水下目标识别的联合互信息特征选择算法。这个算法的核心思想是:利用顺序向前特征搜索机制,在选择出与类别具有最大互信息特征的条件下,选择具有更多互补分类信息的特征,从而达到快速去除噪声特征和冗余特征及提高识别性能的目的。利用4类实测水下目标数据进行仿真实验,结果表明:在支持向量机识别正确

  16. Automatic home medical product recommendation.

    Science.gov (United States)

    Luo, Gang; Thomas, Selena B; Tang, Chunqiang

    2012-04-01

    Web-based personal health records (PHRs) are being widely deployed. To improve PHR's capability and usability, we proposed the concept of intelligent PHR (iPHR). In this paper, we use automatic home medical product recommendation as a concrete application to demonstrate the benefits of introducing intelligence into PHRs. In this new application domain, we develop several techniques to address the emerging challenges. Our approach uses treatment knowledge and nursing knowledge, and extends the language modeling method to (1) construct a topic-selection input interface for recommending home medical products, (2) produce a global ranking of Web pages retrieved by multiple queries, and (3) provide diverse search results. We demonstrate the effectiveness of our techniques using USMLE medical exam cases. PMID:20703712

  17. Autoclass: An automatic classification system

    Science.gov (United States)

    Stutz, John; Cheeseman, Peter; Hanson, Robin

    1991-01-01

    The task of inferring a set of classes and class descriptions most likely to explain a given data set can be placed on a firm theoretical foundation using Bayesian statistics. Within this framework, and using various mathematical and algorithmic approximations, the AutoClass System searches for the most probable classifications, automatically choosing the number of classes and complexity of class descriptions. A simpler version of AutoClass has been applied to many large real data sets, has discovered new independently-verified phenomena, and has been released as a robust software package. Recent extensions allow attributes to be selectively correlated within particular classes, and allow classes to inherit, or share, model parameters through a class hierarchy. The mathematical foundations of AutoClass are summarized.

  18. Field trials of low dose Bayluscide on snail hosts of schistosome and selected non-target organisms in sahelian Cameroon

    Directory of Open Access Journals (Sweden)

    I Takougang

    2006-06-01

    Full Text Available More than 85% of all cases of schistosomiasis in Cameroon occur in the northern sahelian half of the country representing 20% of the population. Several workers have advocated the integrated approach to schistosomiasis control, including snail control, but the death and decay of aquatic organisms, and fish kill that often follows Bayluscide application at the dose of 1g/m³ decrease its acceptability. The present study was designed to assess the effect of lower Bayluscide doses on snail host and non-target fish, frog, the tadpole kill. Bayluscide was applied to study ponds at concentrations of 0, 0.25, 0.5, and 1 g/m³ (ppm. Pre and post application assessment of snails hosts of schistosomes, fish, frog, and tadpole kill were carried out. All 0.25, 0.5, and 1 g/m³ Bayluscide concentrations reduced snail population significantly. Bayluscide concentration of 0.50 g/m³ applied in two rounds of 0.25 g/m³ resulted in high snail mortality and low lethality to fish, frogs, and tadpoles. Further studies are needed to assess the cost-effectiveness of Bayluscide in the control of schistosomiasis following the simplified approach.

  19. Selected issues relating to target companies and their boards in the context of merger and acquisition transactions

    Energy Technology Data Exchange (ETDEWEB)

    Allen, F.R. [Osler, Hoskin and Harcourt, Calgary, AB (Canada)

    1998-12-31

    Some of the practical, legal and regulatory issues which the board of directors of a target company should bear in mind in their deliberations concerning a take-over bid are reviewed. Directors of such companies will require compliance with and adherence to standard legal and regulatory rules of conduct. Developing a team to deal with the myriad details of a take-over, acquisition or merger, preparing and compiling and maintaining a manual of relevant information are highly recommended. Fiduciary duties of directors and its relevance to mergers and acquisitions are illustrated by reference to a number of recent actual court cases involving these issues. Relevant Canadian and U.S. Case Law is reviewed. It is emphasized throughout the paper that take-over transactions, mergers and acquisitions are complex and time consuming processes. It is essential and customary for senior management to be active participants in most merger and acquisition matters to provide the strategic input which drives the efforts of all involved. Equally important is to establish appropriate governance practices and to prepare and equip the corporation`s mergers and acquisitions team in advance, should such events arise on short notice by design or otherwise. 38 refs.

  20. Selected issues relating to target companies and their boards in the context of merger and acquisition transactions

    International Nuclear Information System (INIS)

    Some of the practical, legal and regulatory issues which the board of directors of a target company should bear in mind in their deliberations concerning a take-over bid are reviewed. Directors of such companies will require compliance with and adherence to standard legal and regulatory rules of conduct. Developing a team to deal with the myriad details of a take-over, acquisition or merger, preparing and compiling and maintaining a manual of relevant information are highly recommended. Fiduciary duties of directors and its relevance to mergers and acquisitions are illustrated by reference to a number of recent actual court cases involving these issues. Relevant Canadian and U.S. Case Law is reviewed. It is emphasized throughout the paper that take-over transactions, mergers and acquisitions are complex and time consuming processes. It is essential and customary for senior management to be active participants in most merger and acquisition matters to provide the strategic input which drives the efforts of all involved. Equally important is to establish appropriate governance practices and to prepare and equip the corporation's mergers and acquisitions team in advance, should such events arise on short notice by design or otherwise. 38 refs