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. Automatic Target Detection Using Wavelet Transform

    Directory of Open Access Journals (Sweden)

    Ganesan L

    2004-01-01

    Full Text Available Automatic target recognition (ATR involves processing images for detecting, classifying, and tracking targets embedded in a background scene. This paper presents an algorithm for detecting a specified set of target objects embedded in visual images for an ATR application. The developed algorithm employs a novel technique for automatically detecting man-made and non-man-made single, two, and multitargets from nontarget objects, located within a cluttered environment by evaluating nonoverlapping image blocks, where block-by-block comparison of wavelet cooccurrence feature is done. The results of the proposed algorithm are found to be satisfactory.

  5. 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

  6. Channel selection for automatic seizure detection

    DEFF Research Database (Denmark)

    Duun-Henriksen, Jonas; Kjaer, Troels Wesenberg; Madsen, Rasmus Elsborg

    2012-01-01

    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 detection...

  7. An Approximate Approach to Automatic Kernel Selection.

    Science.gov (United States)

    Ding, Lizhong; Liao, Shizhong

    2016-02-02

    Kernel selection is a fundamental problem of kernel-based learning algorithms. In this paper, we propose an approximate approach to automatic kernel selection for regression from the perspective of kernel matrix approximation. We first introduce multilevel circulant matrices into automatic kernel selection, and develop two approximate kernel selection algorithms by exploiting the computational virtues of multilevel circulant matrices. The complexity of the proposed algorithms is quasi-linear in the number of data points. Then, we prove an approximation error bound to measure the effect of the approximation in kernel matrices by multilevel circulant matrices on the hypothesis and further show that the approximate hypothesis produced with multilevel circulant matrices converges to the accurate hypothesis produced with kernel matrices. Experimental evaluations on benchmark datasets demonstrate the effectiveness of approximate kernel selection.

  8. Towards Automatic Decentralized Control Structure Selection

    DEFF Research Database (Denmark)

    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......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....... 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...

  9. 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...

  10. Biological models for automatic target detection

    Science.gov (United States)

    Schachter, Bruce

    2008-04-01

    Humans are better at detecting targets in literal imagery than any known algorithm. Recent advances in modeling visual processes have resulted from f-MRI brain imaging with humans and the use of more invasive techniques with monkeys. There are four startling new discoveries. 1) The visual cortex does not simply process an incoming image. It constructs a physics based model of the image. 2) Coarse category classification and range-to-target are estimated quickly - possibly through the dorsal pathway of the visual cortex, combining rapid coarse processing of image data with expectations and goals. This data is then fed back to lower levels to resize the target and enhance the recognition process feeding forward through the ventral pathway. 3) Giant photosensitive retinal ganglion cells provide data for maintaining circadian rhythm (time-of-day) and modeling the physics of the light source. 4) Five filter types implemented by the neurons of the primary visual cortex have been determined. A computer model for automatic target detection has been developed based upon these recent discoveries. It uses an artificial neural network architecture with multiple feed-forward and feedback paths. Our implementation's efficiency derives from the observation that any 2-D filter kernel can be approximated by a sum of 2-D box functions. And, a 2-D box function easily decomposes into two 1-D box functions. Further efficiency is obtained by decomposing the largest neural filter into a high pass filter and a more sparsely sampled low pass filter.

  11. 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

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

    Directory of Open Access Journals (Sweden)

    Xavier eVasques

    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/.

  13. 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.

  14. Laser gated viewing : An enabler for Automatic Target Recognition?

    NARCIS (Netherlands)

    Bovenkamp, E.G.P.; Schutte, K.

    2010-01-01

    For many decades attempts to accomplish Automatic Target Recognition have been made using both visual and FLIR camera systems. A recurring problem in these approaches is the segmentation problem, which is the separation between the target and its background. This paper describes an approach to Autom

  15. Time series modeling for automatic target recognition

    Science.gov (United States)

    Sokolnikov, Andre

    2012-05-01

    Time series modeling is proposed for identification of targets whose images are not clearly seen. The model building takes into account air turbulence, precipitation, fog, smoke and other factors obscuring and distorting the image. The complex of library data (of images, etc.) serving as a basis for identification provides the deterministic part of the identification process, while the partial image features, distorted parts, irrelevant pieces and absence of particular features comprise the stochastic part of the target identification. The missing data approach is elaborated that helps the prediction process for the image creation or reconstruction. The results are provided.

  16. Hierarchical Feature Extraction and Selection Method and the Applications in Automatic Target Recognition System%分级特征提取与选择及在自动目标识别系统中的应用

    Institute of Scientific and Technical Information of China (English)

    梅雪; 张继法; 许松松; 巩建鸣

    2012-01-01

    应用于遥感图像、武器制导等的自动目标识别系统中,经常遇到形状相似目标的鉴别问题。为提高其识别的快速性和识别率,提出一种分级的基于形状的目标识别方法。借鉴人类视觉感知方式提取多尺度特征,大尺度下采用全局特征快速粗分类,小尺度下采用局部特征鉴别形状相似目标。然后运用模糊规则对提取的特征进行选择,降低特征维数,加快目标匹配过程。实验结果表明:该方法能快速有效地识别形状相似的目标,特征选择后平均识别率较选择之前提高了6.99/6。%Similar shape object recognition is widely used in automatic target recognition system of remote sensing and weapon guidance. A hierarchical method of shape feature extraction and selection is proposed to increase the recognition efficiency and rate. I.earning from human visual perception, multi-scale features are extracted. C-lobal features are used to make a quick classification,and local features are used to distinguish targets with similar shape. To achieve the feature selection, fuzzy criterion is introduced which improves the matching processing and increases the recognition rate. Experimental results show this method is an effective and general way in recognizing targets with similar shape,and the feature selection improves the recognition rate by 6.9%than before.

  17. Improving Cluster Analysis with Automatic Variable Selection Based on Trees

    Science.gov (United States)

    2014-12-01

    ANALYSIS WITH AUTOMATIC VARIABLE SELECTION BASED ON TREES by Anton D. Orr December 2014 Thesis Advisor: Samuel E. Buttrey Second Reader...DATES COVERED Master’s Thesis 4. TITLE AND SUBTITLE IMPROVING CLUSTER ANALYSIS WITH AUTOMATIC VARIABLE SELECTION BASED ON TREES 5. FUNDING NUMBERS 6...2006 based on classification and regression trees to address problems with determining dissimilarity. Current algorithms do not simultaneously address

  18. 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.

  19. Automatic target recognition based on cross-plot.

    Directory of Open Access Journals (Sweden)

    Kelvin Kian Loong Wong

    Full Text Available Automatic target recognition that relies on rapid feature extraction of real-time target from photo-realistic imaging will enable efficient identification of target patterns. To achieve this objective, Cross-plots of binary patterns are explored as potential signatures for the observed target by high-speed capture of the crucial spatial features using minimal computational resources. Target recognition was implemented based on the proposed pattern recognition concept and tested rigorously for its precision and recall performance. We conclude that Cross-plotting is able to produce a digital fingerprint of a target that correlates efficiently and effectively to signatures of patterns having its identity in a target repository.

  20. 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

  1. Automatic segmentation of brain images: selection of region extraction methods

    Science.gov (United States)

    Gong, Leiguang; Kulikowski, Casimir A.; Mezrich, Reuben S.

    1991-07-01

    In automatically analyzing brain structures from a MR image, the choice of low level region extraction methods depends on the characteristics of both the target object and the surrounding anatomical structures in the image. The authors have experimented with local thresholding, global thresholding, and other techniques, using various types of MR images for extracting the major brian landmarks and different types of lesions. This paper describes specifically a local- binary thresholding method and a new global-multiple thresholding technique developed for MR image segmentation and analysis. The initial testing results on their segmentation performance are presented, followed by a comparative analysis of the two methods and their ability to extract different types of normal and abnormal brain structures -- the brain matter itself, tumors, regions of edema surrounding lesions, multiple sclerosis lesions, and the ventricles of the brain. The analysis and experimental results show that the global multiple thresholding techniques are more than adequate for extracting regions that correspond to the major brian structures, while local binary thresholding is helpful for more accurate delineation of small lesions such as those produced by MS, and for the precise refinement of lesion boundaries. The detection of other landmarks, such as the interhemispheric fissure, may require other techniques, such as line-fitting. These experiments have led to the formulation of a set of generic computer-based rules for selecting the appropriate segmentation packages for particular types of problems, based on which further development of an innovative knowledge- based, goal directed biomedical image analysis framework is being made. The system will carry out the selection automatically for a given specific analysis task.

  2. Signature prediction for model-based automatic target recognition

    Science.gov (United States)

    Keydel, Eric R.; Lee, Shung W.

    1996-06-01

    The moving and stationary target recognition (MSTAR) model- based automatic target recognition (ATR) system utilizes a paradigm which matches features extracted form an unknown SAR target signature against predictions of those features generated from models of the sensing process and candidate target geometries. The candidate target geometry yielding the best match between predicted and extracted features defines the identify of the unknown target. MSTAR will extend the current model-based ATR state-of-the-art in a number of significant directions. These include: use of Bayesian techniques for evidence accrual, reasoning over target subparts, coarse-to-fine hypothesis search strategies, and explicit reasoning over target articulation, configuration, occlusion, and lay-over. These advances also imply significant technical challenges, particularly for the MSTAR feature prediction module (MPM). In addition to accurate electromagnetics, the MPM must provide traceback between input target geometry and output features, on-line target geometry manipulation, target subpart feature prediction, explicit models for local scene effects, and generation of sensitivity and uncertainty measures for the predicted features. This paper describes the MPM design which is being developed to satisfy these requirements. The overall module structure is presented, along with the specific deign elements focused on MSTAR requirements. Particular attention is paid to design elements that enable on-line prediction of features within the time constraints mandated by model-driven ATR. Finally, the current status, development schedule, and further extensions in the module design are described.

  3. 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

    2016-01-08

    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.

  4. Automatic target tracking on multi-resolution terrain

    Institute of Scientific and Technical Information of China (English)

    WAN Ming; ZHANG Wei; MURRAY Marie O.; KAUFMAN Arie

    2006-01-01

    We propose a high-performance path planning algorithm for automatic target tracking in the applications of real-time simulation and visualization of large-scale terrain datasets, with a large number of moving objects (such as vehicles) tracking multiple moving targets. By using a modified Dijkstra's algorithm, an optimal path between each vehicle-target pair over a weighted grid-presented terrain is computed and updated to eliminate the problem of local minima and losing of tracking. Then, a dynamic path re-planning strategy using multi-resolution representation of a dynamic updating region is proposed to achieve high-performance by trading-off precision for efficiency, while guaranteeing accuracy. Primary experimental results showed that our algorithm successfully achieved 10 to 96 frames per second interactive path-replanning rates during a terrain simulation scenario with 10 to 100 vehicles and multiple moving targets.

  5. Automatic attraction of visual attention by supraletter features of former target strings

    DEFF Research Database (Denmark)

    Kyllingsbæk, Søren; Lommel, Sven Van; Bundesen, Claus

    2014-01-01

    , 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. 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.

  7. 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.

  8. 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

  9. Automatic peak selection by a Benjamini-Hochberg-based algorithm.

    Directory of Open Access Journals (Sweden)

    Ahmed Abbas

    Full Text Available 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 [Formula: see text]-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.

  10. 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.

  11. Salient Feature Identification and Analysis using Kernel-Based Classification Techniques for Synthetic Aperture Radar Automatic Target Recognition

    Science.gov (United States)

    2014-03-27

    SALIENT FEATURE IDENTIFICATION AND ANALYSIS USING KERNEL-BASED CLASSIFICATION TECHNIQUES FOR SYNTHETIC APERTURE RADAR AUTOMATIC TARGET RECOGNITION...FEATURE IDENTIFICATION AND ANALYSIS USING KERNEL-BASED CLASSIFICATION TECHNIQUES FOR SYNTHETIC APERTURE RADAR AUTOMATIC TARGET RECOGNITION THESIS Presented...SALIENT FEATURE IDENTIFICATION AND ANALYSIS USING KERNEL-BASED CLASSIFICATION TECHNIQUES FOR SYNTHETIC APERTURE RADAR AUTOMATIC TARGET RECOGNITION

  12. A distributed automatic target recognition system using multiple low resolution sensors

    Science.gov (United States)

    Yue, Zhanfeng; Lakshmi Narasimha, Pramod; Topiwala, Pankaj

    2008-04-01

    In this paper, we propose a multi-agent system which uses swarming techniques to perform high accuracy Automatic Target Recognition (ATR) in a distributed manner. The proposed system can co-operatively share the information from low-resolution images of different looks and use this information to perform high accuracy ATR. An advanced, multiple-agent Unmanned Aerial Vehicle (UAV) systems-based approach is proposed which integrates the processing capabilities, combines detection reporting with live video exchange, and swarm behavior modalities that dramatically surpass individual sensor system performance levels. We employ real-time block-based motion analysis and compensation scheme for efficient estimation and correction of camera jitter, global motion of the camera/scene and the effects of atmospheric turbulence. Our optimized Partition Weighted Sum (PWS) approach requires only bitshifts and additions, yet achieves a stunning 16X pixel resolution enhancement, which is moreover parallizable. We develop advanced, adaptive particle-filtering based algorithms to robustly track multiple mobile targets by adaptively changing the appearance model of the selected targets. The collaborative ATR system utilizes the homographies between the sensors induced by the ground plane to overlap the local observation with the received images from other UAVs. The motion of the UAVs distorts estimated homography frame to frame. A robust dynamic homography estimation algorithm is proposed to address this, by using the homography decomposition and the ground plane surface estimation.

  13. 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.

  14. Automatic air-to-ground target recognition using LWIR FPAs

    Science.gov (United States)

    Amadieu, Jean-Louis; Fraysse, Vincent

    1996-06-01

    The theoretical potential of optical sensors in terms of geometrical resolution makes them the ideal solution for achieving the terminal precision guidance of today's missiles. This paper describes such a sensor, working in the 8 to 12 micrometer spectral domain by using a 64 by 64 IRCCD focal plane array, and whose main mission is to recognize various types of armored vehicles within complex scenes that possibly include other vehicles of similar nature. The target recognition process is based upon a Bayesian approach and can be briefly described as follows: after a classical processing stage that performs the filtering and the multi- thresholding, the target recognition algorithm evaluates a similarity level between the objects, including the target, seen in the IR scene and the 'theoretical' target whose some mean, generic features have been implemented in a database. The surroundings of the target and its orientation in the IR scene are 'a priori' unknown. The similarity level is based on calculation of the Mahalanobis distance between the object features vector and the mean features vector of the model; this calculation involves a covariance matrix which is significant of the errors affecting the measured features and that in particular stem form the limited spatial resolution of the sensor, the detector noise and the sensor- to-target range estimation error. With respect to the sensor hardware, its main opto-mechanical characteristics as well as some electro-optics data are indicates; some examples of target acquisition in complex scenes involving different kinds of IR counter measures are also presented.

  15. 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.

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

    NARCIS (Netherlands)

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

    2011-01-01

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

  17. 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

  18. Kernel sparse coding method for automatic target recognition in infrared imagery using covariance descriptor

    Science.gov (United States)

    Yang, Chunwei; Yao, Junping; Sun, Dawei; Wang, Shicheng; Liu, Huaping

    2016-05-01

    Automatic target recognition in infrared imagery is a challenging problem. In this paper, a kernel sparse coding method for infrared target recognition using covariance descriptor is proposed. First, covariance descriptor combining gray intensity and gradient information of the infrared target is extracted as a feature representation. Then, due to the reason that covariance descriptor lies in non-Euclidean manifold, kernel sparse coding theory is used to solve this problem. We verify the efficacy of the proposed algorithm in terms of the confusion matrices on the real images consisting of seven categories of infrared vehicle targets.

  19. A chest-shape target automatic detection method based on Deformable Part Models

    Science.gov (United States)

    Zhang, Mo; Jin, Weiqi; Li, Li

    2016-10-01

    Automatic weapon platform is one of the important research directions at domestic and overseas, it needs to accomplish fast searching for the object to be shot under complex background. Therefore, fast detection for given target is the foundation of further task. Considering that chest-shape target is common target of shoot practice, this paper treats chestshape target as the target and studies target automatic detection method based on Deformable Part Models. The algorithm computes Histograms of Oriented Gradient(HOG) features of the target and trains a model using Latent variable Support Vector Machine(SVM); In this model, target image is divided into several parts then we can obtain foot filter and part filters; Finally, the algorithm detects the target at the HOG features pyramid with method of sliding window. The running time of extracting HOG pyramid with lookup table can be shorten by 36%. The result indicates that this algorithm can detect the chest-shape target in natural environments indoors or outdoors. The true positive rate of detection reaches 76% with many hard samples, and the false positive rate approaches 0. Running on a PC (Intel(R)Core(TM) i5-4200H CPU) with C++ language, the detection time of images with the resolution of 640 × 480 is 2.093s. According to TI company run library about image pyramid and convolution for DM642 and other hardware, our detection algorithm is expected to be implemented on hardware platform, and it has application prospect in actual system.

  20. Site Selection and Automatically Calculated Rover Traverse for a Lunar Teleoperated Landing Mission

    Science.gov (United States)

    Kamps, Oscar; Foing, Bernard; Flahaut, Jessica

    2016-04-01

    With the recent interest for the Moon, and the plans from the ESA side to do a tele-operated mission from Earth or lunar orbit, it is important to target a well-defined location. One of the major topics to study on the Moon is the existence and availability of volatiles and ices. Because no lander ever visited one of the poles on the Moon the theories with respect to water ice are only based on data from orbiters. In a four month research project the data from the orbiters was used for assessing potential landing sites and a rover traverse planning. Mainly data from the Prospector and LRO were used to select regions of interest. The prior selection was based on slope, temperature and a geological map from the USGS. Three sites on both the North as South Pole were used to test a proposed method for rover traverse planning. Besides the scientific interest, the sites where assessed on its accessibility for landing and roving. This assessment was done based on some assumptions what would be possible for landing and roving. For landing sites it was proposed to pick a site larger than 1km in diameter, in a (partial) illuminated area with a slope lower than 5o, which was inside an area which would be accessible for a rover. The requirements to be selected as accessible area was a slope lower than 20o, the largest polygon which meets this requirement was chosen as accessible area. As destination a site in the PSR was selected which was inside the accessible area and had extremely low temperatures. The boundary for extremely low was defined as 54K which is the sublimation temperature of CO2 in lunar atmospheric pressure. As additional target for the rover a site was selected where the temperature difference would be more than 150K to study volatile migration processes. A combination of tools in ArcGIS were used to do the site selection and rover traverse planning. In the end Rozhdestvensky and Amundsen were selected as most accessible and interesting. After comparing both

  1. 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.

  2. SAR Automatic Target Recognition Based on Numerical Scattering Simulation and Model-based Matching

    Directory of Open Access Journals (Sweden)

    Zhou Yu

    2015-12-01

    Full Text Available This study proposes a model-based Synthetic Aperture Radar (SAR automatic target recognition algorithm. Scattering is computed offline using the laboratory-developed Bidirectional Analytic Ray Tracing software and the same system parameter settings as the Moving and Stationary Target Acquisition and Recognition (MSTAR datasets. SAR images are then created by simulated electromagnetic scattering data. Shape features are extracted from the measured and simulated images, and then, matches are searched. The algorithm is verified using three types of targets from MSTAR data and simulated SAR images, and it is shown that the proposed approach is fast and easy to implement with high accuracy.

  3. Optimizing edge detectors for robust automatic threshold selection : Coping with edge curvature and noise

    NARCIS (Netherlands)

    Wilkinson, Michael H.F.

    1998-01-01

    The Robust Automatic Threshold Selection algorithm was introduced as a threshold selection based on a simple image statistic. The statistic is an average of the grey levels of the pixels in an image weighted by the response at each pixel of a specific edge detector. Other authors have suggested that

  4. 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...

  5. 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)…

  6. 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.

  7. Complete automatic target cuer/recognition system for tactical forward-looking infrared images

    Science.gov (United States)

    Ernisse, Brian E.; Rogers, Steven K.; DeSimio, Martin P.; Raines, Richard A.

    1997-09-01

    A complete forward-looking IR (FLIR) automatic target cuer/recognizer (ATC/R) is presented. The data used for development and testing of this ATC/R are first generation FLIR images collected using a F-15E. The database contains thousands of images with various mission profiles and target arrangements. The specific target of interest is a mobile missile launcher, the primary target. The goal is to locate all vehicles (secondary targets) within a scene and identify the primary targets. The system developed and tested includes an image segmenter, region cluster algorithm, feature extractor, and classifier. Conventional image processing algorithms in conjunction with neural network techniques are used to form a complete ATC/R system. The conventional techniques include hit/miss filtering, difference of Gaussian filtering, and region clustering. A neural network (multilayer perceptron) is used for classification. These algorithms are developed, tested and then combined into a functional ATC/R system. Overall primary target detection rate (cuer) is 84% with a 69% primary target identification (recognizer) rate at ranges relevant to munitions release. Furthermore, the false alarm rate (a nontarget cued as a target) in only 2.3 per scene. The research is being completed with a 10 flight test profile using third generation FLIR images.

  8. Automatic key frame selection using a wavelet-based approach

    Science.gov (United States)

    Campisi, Patrizio; Longari, Andrea; Neri, Alessandro

    1999-10-01

    In a multimedia framework, digital image sequences (videos) are by far the most demanding as far as storage, search, browsing and retrieval requirements are concerned. In order to reduce the computational burden associated to video browsing and retrieval, a video sequence is usually decomposed into several scenes (shots) and each of them is characterized by means of some key frames. The proper selection of these key frames, i.e. the most representative frames in the scene, is of paramount importance for computational efficiency. In this contribution a novel key frame extraction technique based on the wavelet analysis is presented. Experimental results show the capability of the proposed algorithm to select key frames properly summarizing the shot.

  9. Automatic selection of indicators in a fully saturated regression

    DEFF Research Database (Denmark)

    Hendry, David F.; Johansen, Søren; Santos, Carlos

    2008-01-01

    We consider selecting a regression model, using a variant of Gets, when there are more variables than observations, in the special case that the variables are impulse dummies (indicators) for every observation. We show that the setting is unproblematic if tackled appropriately, and obtain the fin...... the finite-sample distribution of estimators of the mean and variance in a simple location-scale model under the null that no impulses matter. A Monte Carlo simulation confirms the null distribution, and shows power against an alternative of interest....

  10. Towards an Automatic and Application-Based EigensolverSelection

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Yeliang; Li, Xiaoye S.; Marques, Osni

    2005-09-09

    The computation of eigenvalues and eigenvectors is an important and often time-consuming phase in computer simulations. Recent efforts in the development of eigensolver libraries have given users good algorithms without the need for users to spend much time in programming. Yet, given the variety of numerical algorithms that are available to domain scientists, choosing the ''best'' algorithm suited for a particular application is a daunting task. As simulations become increasingly sophisticated and larger, it becomes infeasible for a user to try out every reasonable algorithm configuration in a timely fashion. Therefore, there is a need for an intelligent engine that can guide the user through the maze of various solvers with various configurations. In this paper, we present a methodology and a software architecture aiming at determining the best solver based on the application type and the matrix properties. We combine a decision tree and an intelligent engine to select a solver and a preconditioner combination for the application submitted by the user. We also discuss how our system interface is implemented with third party numerical libraries. In the case study, we demonstrate the feasibility and usefulness of our system with a simplified linear solving system. Our experiments show that our proposed intelligent engine is quite adept in choosing a suitable algorithm for different applications.

  11. 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

    2016-04-04

    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.

  12. 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.

  13. 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.

  14. Novel Automatic Filter-Class Feature Selection for Machine Learning Regression

    DEFF Research Database (Denmark)

    Wollsen, Morten Gill; Hallam, John; Jørgensen, Bo Nørregaard

    2016-01-01

    With the increased focus on application of Big Data in all sectors of society, the performance of machine learning becomes essential. Efficient machine learning depends on efficient feature selection algorithms. Filter feature selection algorithms are model-free and therefore very fast, but require...... model in the feature selection process. PCA is often used in machine learning litterature and can be considered the default feature selection method. RDESF outperformed PCA in both experiments in both prediction error and computational speed. RDESF is a new step into filter-based automatic feature...

  15. Novel Automatic Filter-Class Feature Selection for Machine Learning Regression

    DEFF Research Database (Denmark)

    Wollsen, Morten Gill; Hallam, John; Jørgensen, Bo Nørregaard

    2017-01-01

    With the increased focus on application of Big Data in all sectors of society, the performance of machine learning becomes essential. Efficient machine learning depends on efficient feature selection algorithms. Filter feature selection algorithms are model-free and therefore very fast, but require...... model in the feature selection process. PCA is often used in machine learning litterature and can be considered the default feature selection method. RDESF outperformed PCA in both experiments in both prediction error and computational speed. RDESF is a new step into filter-based automatic feature...

  16. Exploring target-selectivity patterns of molecular scaffolds.

    Science.gov (United States)

    Hu, Ye; Bajorath, Jürgen

    2010-05-13

    We investigate the question of whether target-selective molecular scaffolds can be identified on the basis of currently available compound activity data. Starting from a pool of 17745 public domain compounds with activity annotations for 433 human targets, we ultimately identify, through a selectivity classification and database-mining approach, 42 molecular scaffolds represented by multiple compounds that are highly selective for a particular target over one or more others. In many other cases, individual compounds representing unique scaffolds are target-selective. Hence, currently available public domain compound selectivity data are sparse. However, we also identify selectivity patterns that evolve around specific targets and are formed by multiple target-selective scaffolds. These scaffolds should provide interesting starting points for further chemical exploration.

  17. Review of Current Aided/Automatic Target Acquisition Technology for Military Target Acquisition Tasks

    Science.gov (United States)

    2011-07-01

    new advancements in military-relevant performance. C©2011 Society of Photo -Optical Instrumentation Engineers (SPIE). [DOI: 10.1117/1.3601879] Subject...indication (MTI) become first- step candidate approaches. Change detection can be a major tool in improvised explosive detection (IED) detection. Dis- turbed...Wilson, “A time-critical targeting roadmap,” Air Command and Staff Collage , Maxwell AFB, AL, Source Code 405502 ADA420658 (April 2002). 8. J. R. Rufa

  18. Automatic assignment of protein backbone resonances by direct spectrum inspection in targeted acquisition of NMR data.

    Science.gov (United States)

    Wong, Leo E; Masse, James E; Jaravine, Victor; Orekhov, Vladislav; Pervushin, Konstantin

    2008-10-01

    The necessity to acquire large multidimensional datasets, a basis for assignment of NMR resonances, results in long data acquisition times during which substantial degradation of a protein sample might occur. Here we propose a method applicable for such a protein for automatic assignment of backbone resonances by direct inspection of multidimensional NMR spectra. In order to establish an optimal balance between completeness of resonance assignment and losses of cross-peaks due to dynamic processes/degradation of protein, assignment of backbone resonances is set as a stirring criterion for dynamically controlled targeted nonlinear NMR data acquisition. The result is demonstrated with the 12 kDa (13)C,(15) N-labeled apo-form of heme chaperone protein CcmE, where hydrolytic cleavage of 29 C-terminal amino acids is detected. For this protein, 90 and 98% of manually assignable resonances are automatically assigned within 10 and 40 h of nonlinear sampling of five 3D NMR spectra, respectively, instead of 600 h needed to complete the full time domain grid. In addition, resonances stemming from degradation products are identified. This study indicates that automatic resonance assignment might serve as a guiding criterion for optimal run-time allocation of NMR resources in applications to proteins prone to degradation.

  19. Automatic assignment of protein backbone resonances by direct spectrum inspection in targeted acquisition of NMR data

    Energy Technology Data Exchange (ETDEWEB)

    Wong, Leo E. [Nanyang Technological University, School of Biological Sciences (Singapore); Masse, James E. [National Institutes of Health (United States); Jaravine, Victor [J. W. Goethe-University Frankfurt, Institute of Biophysical Chemistry (Germany); Orekhov, Vladislav [Gothenburg University, Swedish NMR Centre (Sweden); Pervushin, Konstantin [Nanyang Technological University, School of Biological Sciences (Singapore)], E-mail: kpervushin@ntu.edu.sg

    2008-10-15

    The necessity to acquire large multidimensional datasets, a basis for assignment of NMR resonances, results in long data acquisition times during which substantial degradation of a protein sample might occur. Here we propose a method applicable for such a protein for automatic assignment of backbone resonances by direct inspection of multidimensional NMR spectra. In order to establish an optimal balance between completeness of resonance assignment and losses of cross-peaks due to dynamic processes/degradation of protein, assignment of backbone resonances is set as a stirring criterion for dynamically controlled targeted nonlinear NMR data acquisition. The result is demonstrated with the 12 kDa {sup 13}C,{sup 15} N-labeled apo-form of heme chaperone protein CcmE, where hydrolytic cleavage of 29 C-terminal amino acids is detected. For this protein, 90 and 98% of manually assignable resonances are automatically assigned within 10 and 40 h of nonlinear sampling of five 3D NMR spectra, respectively, instead of 600 h needed to complete the full time domain grid. In addition, resonances stemming from degradation products are identified. This study indicates that automatic resonance assignment might serve as a guiding criterion for optimal run-time allocation of NMR resources in applications to proteins prone to degradation.

  20. Automatic Quality Measurement and Parameter Selection for Example-based Texture Synthesis

    DEFF Research Database (Denmark)

    Laursen, Lasse Farnung; Clemmensen, Line Katrine Harder; Bærentzen, Jakob Andreas

    cover research to directly estimate specific texture synthesis parameters, such as patch size and iteration convergence, based on input textures. We also examine various similarity measures and evaluate their effectiveness. The goal for each measure is to properly evaluate how well the resulting...... far, automatically selecting parameters suitable for synthesis has been a relatively unexplored topic. In effect, this makes texture synthesis supervised rather than fully automatic. In this technical paper, we propose automatic parameter optimization methods for example based texture synthesis. We...... synthesis compares to the original input. A good similarity measure will enable the search for the optimal texture synthesis parameters by maximizing the quality of the synthesis as a function of parameters. We apply presented methods to a state of the art texture synthesis algorithm, namely the one...

  1. A simulation-based approach towards automatic target recognition of high resolution space borne radar signatures

    Science.gov (United States)

    Anglberger, H.; Kempf, T.

    2016-10-01

    Specific imaging effects that are caused mainly by the range measurement principle of a radar device, its much lower frequency range as compared to the optical spectrum, the slanted imaging geometry and certainly the limited spatial resolution complicates the interpretation of radar signatures decisively. Especially the coherent image formation which causes unwanted speckle noise aggravates the problem of visually recognizing target objects. Fully automatic approaches with acceptable false alarm rates are therefore an even harder challenge. At the Microwaves and Radar Institute of the German Aerospace Center (DLR) the development of methods to implement a robust overall processing workflow for automatic target recognition (ATR) out of high resolution synthetic aperture radar (SAR) image data is under progress. The heart of the general approach is to use time series exploitation for the former detection step and simulation-based signature matching for the subsequent recognition. This paper will show the overall ATR chain as a proof of concept for the special case of airplane recognition on image data from the space borne SAR sensor TerraSAR-X.

  2. 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...

  3. 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

  4. 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.)

  5. Ground moving target processing for tracking selected targets

    Science.gov (United States)

    Nichols, Howard; Majumder, Uttam; Owirka, Gregory; Finn, Lucas

    2016-05-01

    BAE Systems has developed a baseline real-time selected vehicle (SV) radar tracking capability that successfully tracked multiple civilian vehicles in real-world traffic conditions within challenging semi-urban clutter. This real-time tracking capability was demonstrated in laboratory setting. Recent enhancements to the baseline capability include multiple detection modes, improvements to the system-level design, and a wide-area tracking mode. The multiple detection modes support two tracking regimes; wide-area and localized selected vehicle tracking. These two tracking regimes have distinct challenges that may be suited to different trackers. Incorporation of a wide-area tracking mode provides both situational awareness and the potential for enhancing SV track initiation. Improvements to the system-level design simplify the integration of multiple detection modes and more realistic SV track initiation capabilities. Improvements are designed to contribute to a comprehensive tracking capability that exploits a continuous stare paradigm. In this paper, focus will be on the challenges, design considerations, and integration of selected vehicle tracking.

  6. 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

  7. Target and peripheral dose during patient repositioning with the Gamma Knife automatic positioning system (APS) device.

    Science.gov (United States)

    Tran, Tuan-Anh; Stanley, Thomas R; Malhotra, Harish K; De Boer, Steven F; Prasad, Dheerendra; Podgorsak, Matthew B

    2010-01-28

    The GammaPlan treatment planning system does not account for the leakage and scatter dose during APS repositioning. In this study, the dose delivered to the target site and its periphery from the defocus stage and intershot couch transit (couch motion from the focus to defocus position and back) associated with APS repositioning are measured for the Gamma Knife model 4C. A stereotactic head-frame was attached to a Leksell 16 cm diameter spherical phantom with a calibrated ion chamber at its center. Using a fiducial box, CT images of the phantom were acquired and registered in the GammaPlan treatment planning system to determine the coordinates of the target (center of the phantom). An absorbed dose of 10 Gy to the 50% isodose line was prescribed to the target site for all measurements. Plans were generated for the 8, 14 and 18 mm collimator helmets to determine the relationship of measured dose to the number of repositions of the APS system and to the helmet size. The target coordinate was identical throughout entire study and there was no movement of the APS between various shots. This allowed for measurement of intershot transit dose at the target site and its periphery. The couch was paused in the defocus position, allowing defocus dose measurements at the intracranial target and periphery. Measured dose increases with frequency of repositioning and with helmet collimator size. During couch transit, the target receives more dose than peripheral regions; however, in the defocus position, the greatest dose is superior to the target site. The automatic positioning system for the Leksell Gamma Knife model 4C results in an additional dose of up to 3.87 +/- 0.07%, 4.97 +/- 0.04%, and 5.71 +/- 0.07% to the target site; its periphery receives additional dose that varies depending on its position relative to the target. There is also dose contribution to the patient in the defocus position, where the APS repositions the patient from one treatment coordinate to another

  8. Automatic geocoding of high-value targets using structural image analysis and GIS data

    Science.gov (United States)

    Soergel, Uwe; Thoennessen, Ulrich

    1999-12-01

    Geocoding based merely on navigation data and sensor model is often not possible or precise enough. In these cases an improvement of the preregistration through image-based approaches is a solution. Due to the large amount of data in remote sensing automatic geocoding methods are necessary. For geocoding purposes appropriate tie points, which are present in image and map, have to be detected and matched. The tie points are base of the transformation function. Assigning the tie points is combinatorial problem depending on the number of tie points. This number can be reduced using structural tie points like corners or crossings of prominent extended targets (e.g. harbors, airfields). Additionally the reliability of the tie points is improved. Our approach extracts structural tie points independently in the image and in the vector map by a model-based image analysis. The vector map is provided by a GIS using ATKIS data base. The model parameters are extracted from maps or collateral information of the scenario. The two sets of tie points are automatically matched with a Geometric Hashing algorithm. The algorithm was successfully applied to VIS, IR and SAR data.

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

    Science.gov (United States)

    Duncan, Gregg A; Bevan, Michael A

    2015-10-01

    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.

  10. 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...... are classified using the multi-evidence approach. The study is implemented with WorldView-2 multispectral imagery acquired for a study area containing 10 crop classes. The proposed approach is compared with the multi-evidence approach based on training samples selected randomly and border samples based...

  11. 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.

  12. Experimental evaluation of video preprocessing algorithms for automatic target hand-off

    Science.gov (United States)

    McIngvale, P. H.; Guyton, R. D.

    It is pointed out that the Automatic Target Hand-Off Correlator (ATHOC) hardware has been modified to permit operation in a nonreal-time mode as a programmable laboratory test unit using video recordings as inputs and allowing several preprocessing algorithms to be software programmable. In parallel with this hardware modification effort, an analysis and simulation effort has been underway to help determine which of the many available preprocessing algorithms should be implemented in the ATHOC software. It is noted that videotapes from a current technology airborne target acquisition system and an imaging infrared missile seeker were recorded and used in the laboratory experiments. These experiments are described and the results are presented. A set of standard parameters is found for each case. Consideration of the background in the target scene is found to be important. Analog filter cutoff frequencies of 2.5 MHz for low pass and 300 kHz for high pass are found to give best results. EPNC = 1 is found to be slightly better than EPNC = 0. It is also shown that trilevel gives better results than bilevel.

  13. 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.

  14. Deformable mesh registration for the validation of automatic target localization algorithms

    Science.gov (United States)

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

    2013-01-01

    Purpose: To evaluate deformable mesh registration (DMR) as a tool for validating automatic target registration algorithms used during image-guided radiation therapy. Methods: DMR was implemented in a hierarchical model, with rigid, affine, and B-spline transforms optimized in succession to register a pair of surface meshes. The gross tumor volumes (primary tumor and involved lymph nodes) were contoured by a physician on weekly CT scans in a cohort of lung cancer patients and converted to surface meshes. The meshes from weekly CT images were registered to the mesh from the planning CT, and the resulting registered meshes were compared with the delineated surfaces. Known deformations were also applied to the meshes, followed by mesh registration to recover the known deformation. Mesh registration accuracy was assessed at the mesh surface by computing the symmetric surface distance (SSD) between vertices of each registered mesh pair. Mesh registration quality in regions within 5 mm of the mesh surface was evaluated with respect to a high quality deformable image registration. Results: For 18 patients presenting with a total of 19 primary lung tumors and 24 lymph node targets, the SSD averaged 1.3 ± 0.5 and 0.8 ± 0.2 mm, respectively. Vertex registration errors (VRE) relative to the applied known deformation were 0.8 ± 0.7 and 0.2 ± 0.3 mm for the primary tumor and lymph nodes, respectively. Inside the mesh surface, corresponding average VRE ranged from 0.6 to 0.9 and 0.2 to 0.9 mm, respectively. Outside the mesh surface, average VRE ranged from 0.7 to 1.8 and 0.2 to 1.4 mm. The magnitude of errors generally increased with increasing distance away from the mesh. Conclusions: Provided that delineated surfaces are available, deformable mesh registration is an accurate and reliable method for obtaining a reference registration to validate automatic target registration algorithms for image-guided radiation therapy, specifically in regions on or near the target surfaces

  15. 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...

  16. Automatic Weight Selection Algorithm for Designing H Infinity controller for Active Magnetic Bearing

    Directory of Open Access Journals (Sweden)

    Sarath S Nair

    2011-01-01

    Full Text Available In recent times active magnetic bearing has got wide acceptance in industries and other special systems. Current researches focus on improving the disturbance rejection properties of magnetic bearings towork well in industrial environment. So far many controllers have been developed to control the system, of which the H∞ controller is found to guarantee robustness and performance. In this paper an automatic weight selection algorithm is proposed to design robust H Infinity controller automatically for active magnetic bearing system and detailed disturbance analysis is done. This paper focuses on the controller implementation point of view and analyses the variation in control current, peak responses and steady state error of the developed controller. Comparison with a well tuned PID controller shows the efficacy of H infinity controller designed using the proposed algorithm.

  17. 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.

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

    Science.gov (United States)

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

    2012-01-01

    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. 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 < 1 × 10−3), respectively, but the smallest GTVP LE of 2.4 ± 2.1 mm was provided by rereferenced registration (p < 1 × 10−6). Standard registration significantly reduced GTVLN centroid LE to 3.2 ± 2.5 mm (p < 1 × 10−3) compared to bony alignment, with little additional gain offered by the other registration techniques. For simultaneous target alignment, centroid LE as low as 3

  19. 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.

  20. Automatic Selection of Open Source Multimedia Softwares Using Error Back-Propagation Neural Network

    Directory of Open Access Journals (Sweden)

    Deepika

    2015-07-01

    Full Text Available Open source opens a new era to provide license of the software for the user at free of cost which is advantage over paid licensed software. In Multimedia applications there are many versions of software are available and there is a problem for the user to select compatible software for their own system. Most of the time while surfing for software a huge list of software opens in response. The selection of particular software which is pretty suitable for the system from a real big list is the biggest challenge that is faced by the users. This work has been done that focuses on the existing open source software that are widely used and to design an automatic system for selection of particular open source software according to the compatibility of users own system. In this work, error back-propagation based neural network is designed in MATLAB for automatic selection of open source software. The system provides the open source software name after taking the information from user. Regression coefficient of 0.93877 is obtained and the results shown are up to the mark and can be utilized for the fast and effective software search.

  1. 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.

  2. 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

    2016-03-08

    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 radiation 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

  3. 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.

  4. Target-based drug discovery for human African trypanosomiasis: selection of molecular target and chemical matter.

    Science.gov (United States)

    Gilbert, Ian H

    2014-01-01

    Target-based approaches for human African trypanosomiasis (HAT) and related parasites can be a valuable route for drug discovery for these diseases. However, care needs to be taken in selection of both the actual drug target and the chemical matter that is developed. In this article, potential criteria to aid target selection are described. Then the physiochemical properties of typical oral drugs are discussed and compared to those of known anti-parasitics.

  5. Highly accurate SVM model with automatic feature selection for word sense disambiguation

    Institute of Scientific and Technical Information of China (English)

    王浩; 陈贵林; 吴连献

    2004-01-01

    A novel algorithm for word sense disambiguation(WSD) that is based on SVM model improved with automatic feature selection is introduced. This learning method employs rich contextual features to predict the proper senses for specific words. Experimental results show that this algorithm can achieve an execellent performance on the set of data released during the SENSEEVAL-2 competition. We present the results obtained and discuss the transplantation of this algorithm to other languages such as Chinese. Experimental results on Chinese corpus show that our algorithm achieves an accuracy of 70.0 % even with small training data.

  6. 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.

  7. Towards replacing closed with open target selection strategies

    NARCIS (Netherlands)

    Werf, M.J. van der

    2005-01-01

    Increasingly, microbial production processes are being improved by targeted approaches. In directed strain improvement, the selection of the relevant targets is the limiting step in metabolic engineering. Currently, the identification of leads is still a random process relying largely on expert know

  8. 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.

  9. A statistically based seasonal precipitation forecast model with automatic predictor selection and its application to central and south Asia

    Science.gov (United States)

    Gerlitz, Lars; Vorogushyn, Sergiy; Apel, Heiko; Gafurov, Abror; Unger-Shayesteh, Katy; Merz, Bruno

    2016-11-01

    The study presents a statistically based seasonal precipitation forecast model, which automatically identifies suitable predictors from globally gridded sea surface temperature (SST) and climate variables by means of an extensive data-mining procedure and explicitly avoids the utilization of typical large-scale climate indices. This leads to an enhanced flexibility of the model and enables its automatic calibration for any target area without any prior assumption concerning adequate predictor variables. Potential predictor variables are derived by means of a cell-wise correlation analysis of precipitation anomalies with gridded global climate variables under consideration of varying lead times. Significantly correlated grid cells are subsequently aggregated to predictor regions by means of a variability-based cluster analysis. Finally, for every month and lead time, an individual random-forest-based forecast model is constructed, by means of the preliminary generated predictor variables. Monthly predictions are aggregated to running 3-month periods in order to generate a seasonal precipitation forecast. The model is applied and evaluated for selected target regions in central and south Asia. Particularly for winter and spring in westerly-dominated central Asia, correlation coefficients between forecasted and observed precipitation reach values up to 0.48, although the variability of precipitation rates is strongly underestimated. Likewise, for the monsoonal precipitation amounts in the south Asian target area, correlations of up to 0.5 were detected. The skill of the model for the dry winter season over south Asia is found to be low. A sensitivity analysis with well-known climate indices, such as the El Niño- Southern Oscillation (ENSO), the North Atlantic Oscillation (NAO) and the East Atlantic (EA) pattern, reveals the major large-scale controlling mechanisms of the seasonal precipitation climate for each target area. For the central Asian target areas, both

  10. 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.

  11. Investigation of measureable parameters that correlate with automatic target recognition performance in synthetic aperture sonar

    Science.gov (United States)

    Gazagnaire, Julia; Cobb, J. T.; Isaacs, Jason

    2015-05-01

    There is a desire in the Mine Counter Measure community to develop a systematic method to predict and/or estimate the performance of Automatic Target Recognition (ATR) algorithms that are detecting and classifying mine-like objects within sonar data. Ideally, parameters exist that can be measured directly from the sonar data that correlate with ATR performance. In this effort, two metrics were analyzed for their predictive potential using high frequency synthetic aperture sonar (SAS) images. The first parameter is a measure of contrast. It is essentially the variance in pixel intensity over a fixed partition of relatively small size. An analysis was performed to determine the optimum block size for this contrast calculation. These blocks were then overlapped in the horizontal and vertical direction over the entire image. The second parameter is the one-dimensional K-shape parameter. The K-distribution is commonly used to describe sonar backscatter return from range cells that contain a finite number of scatterers. An Ada-Boosted Decision Tree classifier was used to calculate the probability of classification (Pc) and false alarm rate (FAR) for several types of targets in SAS images from three different data sets. ROC curves as a function of the measured parameters were generated and the correlation between the measured parameters in the vicinity of each of the contacts and the ATR performance was investigated. The contrast and K-shape parameters were considered separately. Additionally, the contrast and K-shape parameter were associated with background texture types using previously labeled high frequency SAS images.

  12. Comparative analysis of different implementations of a parallel algorithm for automatic target detection and classification of hyperspectral images

    Science.gov (United States)

    Paz, Abel; Plaza, Antonio; Plaza, Javier

    2009-08-01

    Automatic target detection in hyperspectral images is a task that has attracted a lot of attention recently. In the last few years, several algoritms have been developed for this purpose, including the well-known RX algorithm for anomaly detection, or the automatic target detection and classification algorithm (ATDCA), which uses an orthogonal subspace projection (OSP) approach to extract a set of spectrally distinct targets automatically from the input hyperspectral data. Depending on the complexity and dimensionality of the analyzed image scene, the target/anomaly detection process may be computationally very expensive, a fact that limits the possibility of utilizing this process in time-critical applications. In this paper, we develop computationally efficient parallel versions of both the RX and ATDCA algorithms for near real-time exploitation of these algorithms. In the case of ATGP, we use several distance metrics in addition to the OSP approach. The parallel versions are quantitatively compared in terms of target detection accuracy, using hyperspectral data collected by NASA's Airborne Visible Infra-Red Imaging Spectrometer (AVIRIS) over the World Trade Center in New York, five days after the terrorist attack of September 11th, 2001, and also in terms of parallel performance, using a massively Beowulf cluster available at NASA's Goddard Space Flight Center in Maryland.

  13. Target selection and transfer trajectories design for exploring asteroid mission

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    Technique of target selection and profiles of transfer trajectory for Chinese asteroid exploring mission are studied systemically.A complete set of approaches to selecting mission targets and designing the transfer trajectory is proposed.First,when selecting a target for mission,some factors regarded as the scientific motivations are discussed.Then,when analyzing the accessibility of targets,instead of the classical strategy,the multiple gravity-assist strategy is provided.The suitable and possible targets,taking into account scientific value and technically feasible,are obtained via selection and estimation.When designing the transfer trajectory for exploring asteroid mission,an approach to selecting gravity-assist celestial body is proposed.Finally,according to the mission constraints,the trajectory profile with 2-years △V-EGA for exploring asteroid is presented.Through analyzing the trajectory profile,unexpected result that the trajectory would pass by two main-belts asteroids is found.So,the original proposal is extended to the multiple flybys mission.It adds the scientific return for asteroid mission.

  14. Non-coplanar automatic beam orientation selection in cranial IMRT: a practical methodology

    Energy Technology Data Exchange (ETDEWEB)

    Llacer, Jorge [EC Engineering Consultants LLC, 130 Forest Hill Drive, Los Gatos, CA 95032 (United States); Li Sicong [Department of Radiation Oncology, University of Nebraska Medical Center, Omaha, NE 68198 (United States); Agazaryan, Nzhde; Solberg, Timothy D [Department of Radiation Oncology, University of California, Los Angeles, CA 90095 (United States); Promberger, Claus [BrainLAB AG, Kapellenstrasse 12, 85622 Feldkirchen (Germany)], E-mail: escalivat@jllacer.com, E-mail: sl1@unmc.edu, E-mail: NAgazaryan@mednet.ucla.edu, E-mail: claus.promberger@brainlab.com, E-mail: Timothy.Solberg@utsouthwestern.edu

    2009-03-07

    This paper proposes a method for automatic selection of beam orientations in non-coplanar cranial IMRT. Methods of computer vision, beam's eye view techniques and neural networks are used to define a new geometry-based methodology that leads to treatment plans for cranial lesions that are comparable in quality to those generated by experienced radiation physicists. The automatic beam selection (ABS) process can be carried out in clinically useful computation times, in 1 min or less for most cases. In the process of describing the ABS process, it is shown that the cranial beam orientation optimization problem is mathematically ill posed, with the expectation that a large number of solutions will lead to similar results. Nevertheless, there are better and worse solutions and we show that the proposed ABS process, by its design, has to lead to one of the better ones. We have carried out extensive tests with 14 patients with beam selection tasks ranging from the rather simple to quite complex. The ABS process has always yielded optimizations with results that are considered good for clinic use. Seven-beam coplanar optimizations for some of the patients have also been investigated. Comparisons with non-coplanar optimizations indicate in which cases the simpler coplanar plans can be used to advantage. Parameters used in the comparisons are dose-volume histograms, minimum and maximum PTV doses, equivalent uniform doses for the PTV and OARs, and treatment volume, conformity and normal tissue indices. It is felt that the current ABS methodology is ready for extensive clinical tests.

  15. Band selection method based on spectrum difference in targets of interest in hyperspectral imagery

    Science.gov (United States)

    Zhang, Xiaohan; Yang, Guang; Yang, Yongbo; Huang, Junhua

    2016-10-01

    While hyperspectral data shares rich spectrum information, it has numbers of bands with high correlation coefficients, causing great data redundancy. A reasonable band selection is important for subsequent processing. Bands with large amount of information and low correlation should be selected. On this basis, according to the needs of target detection applications, the spectral characteristics of the objects of interest are taken into consideration in this paper, and a new method based on spectrum difference is proposed. Firstly, according to the spectrum differences of targets of interest, a difference matrix which represents the different spectral reflectance of different targets in different bands is structured. By setting a threshold, the bands satisfying the conditions would be left, constituting a subset of bands. Then, the correlation coefficients between bands are calculated and correlation matrix is given. According to the size of the correlation coefficient, the bands can be set into several groups. At last, the conception of normalized variance is used on behalf of the information content of each band. The bands are sorted by the value of its normalized variance. Set needing number of bands, and the optimum band combination solution can be get by these three steps. This method retains the greatest degree of difference between the target of interest and is easy to achieve by computer automatically. Besides, false color image synthesis experiment is carried out using the bands selected by this method as well as other 3 methods to show the performance of method in this paper.

  16. 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...

  17. Target Selection for the LBTI Exozodi Key Science Program

    CERN Document Server

    Weinberger, Alycia J; Kennedy, Grant M; Roberge, Aki; Defrère, Denis; Hinz, Philip M; Millan-Gabet, Rafael; Rieke, George; Bailey, Vanessa P; Danchi, William C; Haniff, Chris; Mennesson, Bertrand; Serabyn, Eugene; Skemer, Andrew J; Stapelfeldt, Karl R; Wyatt, Mark C

    2015-01-01

    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 ...

  18. Target selection and determination of function in structural genomics.

    Science.gov (United States)

    Watson, James D; Todd, Annabel E; Bray, James; Laskowski, Roman A; Edwards, Aled; Joachimiak, Andrzej; Orengo, Christine A; Thornton, Janet M

    2003-01-01

    The first crucial step in any structural genomics project is the selection and prioritization of target proteins for structure determination. There may be a number of selection criteria to be satisfied, including that the proteins have novel folds, that they be representatives of large families for which no structure is known, and so on. The better the selection at this stage, the greater is the value of the structures obtained at the end of the experimental process. This value can be further enhanced once the protein structures have been solved if the functions of the given proteins can also be determined. Here we describe the methods used at either end of the experimental process: firstly, sensitive sequence comparison techniques for selecting a high-quality list of target proteins, and secondly the various computational methods that can be applied to the eventual 3D structures to determine the most likely biochemical function of the proteins in question.

  19. 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.

  20. [Recommendations for selecting antimicrobial agents for in vitro susceptibility studies using automatic and semiautomatic systems].

    Science.gov (United States)

    Cantón, Rafael; Alós, Juan Ignacio; Baquero, Fernando; Calvo, Jorge; Campos, José; Castillo, Javier; Cercenado, Emilia; Domínguez, M Angeles; Liñares, Josefina; López-Cerezo, Lorena; Marco, Francesc; Mirelis, Beatriz; Morosini, María-Isabel; Navarro, Ferran; Oliver, Antonio; Pérez-Trallero, Emilio; Torres, Carmen; Martínez-Martínez, Luis

    2007-01-01

    The number of clinical microbiology laboratories that have incorporated automatic susceptibility testing devices has increased in recent years. The majority of these systems determine MIC values using microdilution panels or specific cards, with grouping into clinical categories (susceptible, intermediate or resistant) and incorporate expert systems to infer resistance mechanisms. This document presents the recommendations of a group of experts designated by Grupo de Estudio de los Mecanismos de Acción y Resistencia a los Antimicrobianos (GEMARA, Study group on mechanisms of action and resistance to antimicrobial agents) and Mesa Española de Normalización de la Sensibilidad y Resistencia a los Antimicrobianos (MENSURA, Spanish Group for Normalizing Antimicrobial Susceptibility and Antimicrobial Resistance), with the aim of including antimicrobial agents and selecting concentrations for the susceptibility testing panels of automatic systems. The following have been defined: various antimicrobial categories (A: must be included in the study panel; B: inclusion is recommended; and C: inclusion is secondary, but may facilitate interpretative reading of the antibiogram) and groups (0: not used in therapeutics but may facilitate the detection of resistance mechanisms; 1: must be studied and always reported; 2: must be studied and selectively reported; 3: must be studied and reported at a second level; and 4: should be studied in urinary tract pathogens isolated in urine and other specimens). Recommended antimicrobial concentrations are adapted from the breakpoints established by EUCAST, CLSI and MENSURA. This approach will lead to more accurate susceptibility testing results with better detection of resistance mechanisms, and allowing to reach the clinical goal of the antibiogram.

  1. 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.

  2. Pattern-Based Target Selection Applied to Fund Raising

    NARCIS (Netherlands)

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

    2001-01-01

    textabstractThis paper proposes a new algorithm for target selection. This algorithm collects all frequent patterns (equivalent to frequent item sets) in a training set. These patterns are stored e?ciently using a compact data structure called a trie. For each pattern the relative frequency of the t

  3. 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

  4. Selective target processing: perceptual load or distractor salience?

    Science.gov (United States)

    Eltiti, Stacy; Wallace, Denise; Fox, Elaine

    2005-07-01

    Perceptual load theory (Lavie, 1995) states that participants cannot engage in focused attention when shown displays containing a low perceptual load, because attentional resources are not exhausted, whereas in high-load displays attention is always focused, because attentional resources are exhausted. An alternative "salience" hypothesis holds that the salience of distractors and not perceptual load per se determines selective attention. Three experiments were conducted to investigate the influence that target and distractor onsets and offsets have on selective processing in a standard interference task. Perceptual load theory predicts that, regardless of target or distractor presentation (onset or offset), interference from ignored distractors should occur in low-load displays only. In contrast, the salience hypothesis predicts that interference should occur when the distractor appears as an onset and would occur for distractor offsets only when the target was also an offset. Interference may even occur in highload displays if the distractor is more salient. The results supported the salience hypothesis.

  5. An active contour-based atlas registration model applied to automatic subthalamic nucleus targeting on MRI: method and validation.

    Science.gov (United States)

    Duay, Valérie; Bresson, Xavier; Castro, Javier Sanchez; Pollo, Claudio; Cuadra, Meritxell Bach; Thiran, Jean-Philippe

    2008-01-01

    This paper presents a new non parametric atlas registration framework, derived from the optical flow model and the active contour theory, applied to automatic subthalamic nucleus (STN) targeting in deep brain stimulation (DBS) surgery. In a previous work, we demonstrated that the STN position can be predicted based on the position of surrounding visible structures, namely the lateral and third ventricles. A STN targeting process can thus be obtained by registering these structures of interest between a brain atlas and the patient image. Here we aim to improve the results of the state of the art targeting methods and at the same time to reduce the computational time. Our simultaneous segmentation and registration model shows mean STN localization errors statistically similar to the most performing registration algorithms tested so far and to the targeting expert's variability. Moreover, the computational time of our registration method is much lower, which is a worthwhile improvement from a clinical point of view.

  6. 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.

  7. Signatures of DNA target selectivity by ETS transcription factors.

    Science.gov (United States)

    Poon, Gregory M K; Kim, Hye Mi

    2017-03-16

    The ETS family of transcription factors is a functionally heterogeneous group of gene regulators that share a structurally conserved, eponymous DNA-binding domain. DNA target specificity derives from combinatorial interactions with other proteins as well as intrinsic heterogeneity among ETS domains. Emerging evidence suggests molecular hydration as a fundamental feature that defines the intrinsic heterogeneity in DNA target selection and susceptibility to epigenetic DNA modification. This perspective invokes novel hypotheses in the regulation of ETS proteins in physiologic osmotic stress, their pioneering potential in heterochromatin, and the effects of passive and pharmacologic DNA demethylation on ETS regulation.

  8. 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)

  9. Peptide-functionalized nanoparticles for selective targeting of pancreatic tumor.

    Science.gov (United States)

    Valetti, Sabrina; Maione, Federica; Mura, Simona; Stella, Barbara; Desmaële, Didier; Noiray, Magali; Vergnaud, Juliette; Vauthier, Christine; Cattel, Luigi; Giraudo, Enrico; Couvreur, Patrick

    2014-10-28

    Chemotherapy for pancreatic cancer is hampered by the tumor's physio-pathological complexity. Here we show a targeted nanomedicine using a new ligand, the CKAAKN peptide, which had been identified by phage display, as an efficient homing device within the pancreatic pathological microenvironment. Taking advantage of the squalenoylation platform, the CKAAKN peptide was conjugated to squalene (SQCKAAKN) and then co-nanoprecipitated with the squalenoyl prodrug of gemcitabine (SQdFdC) giving near monodisperse nanoparticles (NPs) for safe intravenous injection. By interacting with a novel target pathway, the Wnt-2, the CKAAKN functionalization enabled nanoparticles: (i) to specifically interact with both tumor cells and angiogenic vessels and (ii) to simultaneously promote pericyte coverage, thus leading to the normalization of the vasculature likely improving the tumor accessibility for therapy. All together, this approach represents a unique targeted nanoparticle design with remarkable selectivity towards pancreatic cancer and multiple mechanisms of action.

  10. Selection and trajectory design to mission secondary targets

    Science.gov (United States)

    Victorino Sarli, Bruno; Kawakatsu, Yasuhiro

    2017-02-01

    Recently, with new trajectory design techniques and use of low-thrust propulsion systems, missions have become more efficient and cheaper with respect to propellant. As a way to increase the mission's value and scientific return, secondary targets close to the main trajectory are often added with a small change in the transfer trajectory. As a result of their large number, importance and facility to perform a flyby, asteroids are commonly used as such targets. This work uses the Primer Vector theory to define the direction and magnitude of the thrust for a minimum fuel consumption problem. The design of a low-thrust trajectory with a midcourse asteroid flyby is not only challenging for the low-thrust problem solution, but also with respect to the selection of a target and its flyby point. Currently more than 700,000 minor bodies have been identified, which generates a very large number of possible flyby points. This work uses a combination of reachability, reference orbit, and linear theory to select appropriate candidates, drastically reducing the simulation time, to be later included in the main trajectory and optimized. Two test cases are presented using the aforementioned selection process and optimization to add and design a secondary flyby to a mission with the primary objective of 3200 Phaethon flyby and 25143 Itokawa rendezvous.

  11. 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.

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

    Science.gov (United States)

    Court, Laurence E; Tishler, Roy B; Petit, Joshua; Cormack, Robert; Chin, Lee

    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 degrees, 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

  13. 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.

  14. Improvement of Sample Selection: A Cascade-Based Approach for Lesion Automatic Detection

    Directory of Open Access Journals (Sweden)

    Shofwatul ‘Uyun

    2016-04-01

    Full Text Available Computer-Aided Detection (CADe system has a significant role as a preventative effort in the early detection of breast cancer. There are some phases in developing the pattern recognition on the CADe system, including the availability of a large number of data, feature extraction, selection and use of features, and the selection of the appropriate classification method. Haar cascade classifier has been successfully developed to detect the faces in the multimedia image automatically and quickly. The success of the face detection system must not be separated from the availability of the training data in the large numbers. However, it is not easy to implement on a medical image because of some reasons, including its low quality, the very little gray-value differences, and the limited number of the patches for the examples of the positive data. Therefore, this research proposes an algorithm to overcome the limitation of the number of patches on the region of interest to detect whether the lesion exists or not on the mammogram images based on the Haar cascade classifier. This research uses the mammogram and ultrasonography images from the breast imaging of 60 probands and patients in the Clinic of Oncology, Yogyakarta. The testing of the CADe system is done by comparing the reading result of that system with the mammography reading result validated with the reading of the ultrasonography image by the Radiologist. The testing result of the k-fold cross validation demonstrates that the use of the algorithm for the multiplication of intersection rectangle may improve the system performance with accuracy, sensitivity, and specificity of 76%, 89%, and 63%, respectively.

  15. Automatic Focusing for a 675 GHz Imaging Radar with Target Standoff Distances from 14 to 34 Meters

    Science.gov (United States)

    Tang, Adrian; Cooper, Ken B.; Dengler, Robert J.; Llombart, Nuria; Siegel, Peter H.

    2013-01-01

    This paper dicusses the issue of limited focal depth for high-resolution imaging radar operating over a wide range of standoff distances. We describe a technique for automatically focusing a THz imaging radar system using translational optics combined with range estimation based on a reduced chirp bandwidth setting. The demonstarted focusing algorithm estimates the correct focal depth for desired targets in the field of view at unknown standoffs and in the presence of clutter to provide good imagery at 14 to 30 meters of standoff.

  16. Adaptive Procurement Guidelines for Automatic Selection of Renewable Forest Energy Sources within a Sustainable Energy Production System

    Directory of Open Access Journals (Sweden)

    Teijo Palander

    2016-03-01

    Full Text Available An automatic forest-stand selection method was developed that integrates the procurement of profitable energy sources within a sustainable energy production system. We tested the method using a forest harvester simulator. We found that site-specific estimates of forest characteristics are important when predicting the potential of an energy-wood stand as a renewable energy source. Further, tree parameters can be combined with automatic stem measurements from a multiple-tree harvester to predict the energy-wood biomass in the stands. The selection process uses data from profitability studies. The selection process also uses environmental criteria to ensure that sufficient soil organic matter is left behind and to protect the soil against erosion. The integrated system of the harvester automatically adapts the system’s models and stand-selection rules to account for various site-specific stand parameters. Predicting the profitable and environmentally acceptable yield of stand biomass has great potential in sustainable forest resource management, but managers must decide whether the operational procurement guidelines provided by the stand-selection method is acceptable under their local real-world wood procurement conditions.

  17. 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

  18. 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

  19. 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.

  20. A convergent mean shift algorithm to select targets for LAMOST

    Institute of Scientific and Technical Information of China (English)

    Guang-Wei Li; Gang Zhao

    2009-01-01

    This paper firstly finds that the Mean Shift Algorithm used by the Observation Control System (OCS) Research Group of the University of Science and Technology of China in Survey Strategy System 2.10 (SSS2.10) to select targets for the Large Sky Area Multi-Object Fiber Spectroscopic Telescope (LAMOST) is not convergent in theory. By carefully studying the mathematical formulation of the Mean Shift Algorithm, we find that it tries to find a point where some objective function achieves its maximum value; the Mean Shift Vector can be regarded as the ascension direction for the objective function. If we regard the objective function as the numerical description for the imaging quality of all targets covered by the focal panel, then the Mean Shift Algorithm can find the place where the imaging quality is the best. So, the problem of selecting targets is equal to the problem of finding the place where the imaging quality is the best. In addition, we also give some effective heuristics to improve computational speed and propose an effective method to assign point sources to the respective fibers. As a result, our program runs fast, and it costs only several seconds to generate an observation.

  1. Automatic Labelling and Selection of Training Samples for High-Resolution Remote Sensing Image Classification over Urban Areas

    Directory of Open Access Journals (Sweden)

    Xin Huang

    2015-12-01

    Full Text Available Supervised classification is the commonly used method for extracting ground information from images. However, for supervised classification, the selection and labelling of training samples is an expensive and time-consuming task. Recently, automatic information indexes have achieved satisfactory results for indicating different land-cover classes, which makes it possible to develop an automatic method for labelling the training samples instead of manual interpretation. In this paper, we propose a method for the automatic selection and labelling of training samples for high-resolution image classification. In this way, the initial candidate training samples can be provided by the information indexes and open-source geographical information system (GIS data, referring to the representative land-cover classes: buildings, roads, soil, water, shadow, and vegetation. Several operations are then applied to refine the initial samples, including removing overlaps, removing borders, and semantic constraints. The proposed sampling method is evaluated on a series of high-resolution remote sensing images over urban areas, and is compared to classification with manually labeled training samples. It is found that the proposed method is able to provide and label a large number of reliable samples, and can achieve satisfactory results for different classifiers. In addition, our experiments show that active learning can further enhance the classification performance, as active learning is used to choose the most informative samples from the automatically labeled samples.

  2. 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.

  3. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Sanchez Castro, F.J.; Cuisenaire, O.; Thiran, J.P. [Ecole Polytechnique Federale de Lausanne (EPFL) (Switzerland). Signal Processing Inst.; Pollo, C. [Ecole Polytechnique Federale de Lausanne (EPFL) (Switzerland). Signal Processing Inst.; Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne (Switzerland). Dept. of Neurosurgery; Villemure, J.G. [Centre Hospitalier Universitaire Vaudois (CHUV), Lausanne (Switzerland). Dept. of Neurosurgery

    2006-03-15

    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.)

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

    OpenAIRE

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

    2014-01-01

    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...

  6. 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.

  7. 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.

  8. 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

  9. Robustness of features for automatic target discrimination in high resolution polarimetric SAR data.

    NARCIS (Netherlands)

    Broek, A.C. van den; Dekker, R.J.; Steeghs, P.

    2003-01-01

    We have studied the robustness of features against aspect variability for the purpose of target discrimination using polarimetric 35 Ghz ISAR data. Images at a resolution of 10 cm and 30 cm have been used for a complete aspect range of 360 degrees. The data covered four military targets: T72, ZSU23/

  10. The Role of Feature Enhanced Processing for Automatic Target Recognition using High Resolution Polarimetric SAR Data

    NARCIS (Netherlands)

    Broek, A.C. van den; Steeghs, T.P.H.; Dekker, R.J.

    2005-01-01

    We have studied the effect of feature enhanced processing on the discrimination of targets in highresolution polarimetric ISAR and SAR images. This is done by comparing feature-based classification results for original images and images which have been pre-processed to enhance target features. The d

  11. 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...

  12. 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.)

  13. 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.

  14. 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 ...

  15. 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.

  16. Systematic Assessment of Molecular Selectivity at the Level of Targets, Bioactive Compounds, and Structural Analogues.

    Science.gov (United States)

    Hu, Ye; Bajorath, Jürgen

    2016-06-20

    Through systematic mining of compound activity data, the target selectivity of bioactive compounds was systematically explored. The analysis was facilitated by applying, extending, and combining the concepts of target cliffs, selectivity cliffs, and matched molecular pairs. Selectivity relationships were explored at different levels including targets, individual bioactive compounds, and pairs of structural analogues. A variety of targets were identified for which active compounds were consistently nonselective or, by contrast, exclusively selective, making it possible to prioritize, or de-prioritize, targets for compound development. Furthermore, many chemical modifications were detected that altered compound selectivity in a well-defined manner including small structural changes that converted nonselective into target-selective compounds or inverted the target selectivity of active compounds. A large knowledge base of selectivity relationships across pharmaceutical targets and chemical modifications that alter selectivity was generated; this has been made freely available to the scientific community as a part of this investigation.

  17. Targets of balancing selection in the human genome

    DEFF Research Database (Denmark)

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

    2009-01-01

    Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant...... that although balancing selection may not have an obvious impact on a large proportion of human genes, it is a key force affecting the evolution of a number of genes in humans.......Balancing selection is potentially an important biological force for maintaining advantageous genetic diversity in populations, including variation that is responsible for long-term adaptation to the environment. By serving as a means to maintain genetic variation, it may be particularly relevant...... 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...

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

    Energy Technology Data Exchange (ETDEWEB)

    Tacke, Martin B.; Nill, Simeon; Krauss, Andreas; Oelfke, Uwe [Department of Medical Physics in Radiation Oncology, German Cancer Research Center, Im Neuenheimer Feld 280, D-69120 Heidelberg (Germany)

    2010-02-15

    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

  19. Combining synthetic image generation and AI to aid automatic target recognizers

    Science.gov (United States)

    Keller, R.; Juarez, J.; Prater, M.; Balaban, T.

    1987-01-01

    The user-friendly, Band-Independent Signature Prediction (BISP) model has been developed for the recognition of real-world targets in complex backgrounds and under variable environmental conditions and operating states, through the use of a signature-prediction capability that can be used in conjunction with a natural language description of the recognition context to determine both the features and the feature strengths for the specified context. BISP's signature-prediction capability can be used to design a context-adaptive target recognizer that is based on either classical pattern recognition principles or on more advanced but less mature learning networks akin to those of emerging 'neurocomputers'.

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

    Science.gov (United States)

    Weinmann, Hilmar

    2016-03-04

    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.

  1. Optimization of Automatic Target Recognition with a Reject Option Using Fusion and Correlated Sensor Data

    Science.gov (United States)

    2005-04-25

    ROC curve in the evaluation of machine learning algorithms,” Pattern Recognition, Vol 30, No 7: 1145-1159 (1997). Brown, Gerald G. “Top Ten Secrets...Kuo C. and Karp , Sherman. “Polarimetric fusion for synthetic aperture radar target classification,” Pattern Recognition, Vol 30, No 5: 769-775

  2. 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.

  3. 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...

  4. Automatic selection of an optimal systolic and diastolic reconstruction windows for dual-source CT coronary angiography

    Science.gov (United States)

    Seifarth, H.; Puesken, M.; Wienbeck, S.; Maintz, D.; Heindel, W.; Juergens, K.-U.

    2008-03-01

    Purpose: To assess the performance of a motion map algorithm to automatically determine the optimal systolic and diastolic reconstruction window for coronary CT Angiography using Dual Source CT. Materials and Methods: Dual Source coronary CT angiography data sets (Somatom Definition, Siemens Medical Solutions) from 50 consecutive patients were included in the analysis. Optimal systolic and diastolic reconstruction windows were determined using a motion map algorithm (BestPhase, Siemens Medical Solutions). Additionally data sets were reconstructed in 5% steps throughout the RR-interval. For each major vessel (RCA, LAD and LCX) an optimal systolic and diastolic reconstruction window was manually determined by two independent readers using volume rendering displays. Image quality was rated using a five-point scale (1 = no motion artifacts, 5 = severe motion artifacts over entire length of the vessel). Results: The mean heart rate during the scan was 72.4bpm (+/-15.8bpm). Median systolic and diastolic reconstruction windows using the BestPhase algorithm were at 37% and 73% RR. The median manually selected systolic reconstruction window was 35 %, 30% and 35% for RCA, LAD, and LCX. For all vessels the median observer selected diastolic reconstruction window was 75%. Mean image quality using the BestPhase algorithm was 2.4 +/-0.9 for systolic reconstructions and 1.9 +/-1.1 for diastolic reconstructions. Using the manual approach, the mean image quality was 1.9 +/-0.5 and 1.7 +/-0.8 respectively. There was a significant difference in image quality between automatically and manually determined systolic reconstructions (p<0.01) but there was no significant difference in image quality in diastolic reconstructions. Conclusion: Automatic determination of the optimal reconstruction interval using the BestPhase algorithm is feasible and yields reconstruction windows similar to observer selected reconstruction windows. In diastolic reconstructions overall image quality is similar

  5. Portable automatic bioaerosol sampling system for rapid on-site detection of targeted airborne microorganisms.

    Science.gov (United States)

    Usachev, Evgeny V; Pankova, Anna V; Rafailova, Elina A; Pyankov, Oleg V; Agranovski, Igor E

    2012-10-26

    Bioaerosols could cause various severe human and animal diseases and their opportune and qualitative precise detection and control is becoming a significant scientific and technological topic for consideration. Over the last few decades bioaerosol detection has become an important bio-defense related issue. Many types of portable and stationary bioaerosol samplers have been developed and, in some cases, integrated into automated detection systems utilizing various microbiological techniques for analysis of collected microbes. This paper describes a personal sampler used in conjunction with a portable real-time PCR technique. It was found that a single fluorescent dye could be successfully used in multiplex format for qualitative detection of numerous targeted bioaerosols in one PCR tube making the suggested technology a reliable "first alert" device. This approach has been specifically developed and successfully verified for rapid detection of targeted microorganisms by portable PCR devices, which is especially important under field conditions, where the number of microorganisms of interest usually exceeds the number of available PCR reaction tubes. The approach allows detecting targeted microorganisms and triggering some corresponding sanitary and quarantine procedures to localize possible spread of dangerous infections. Following detailed analysis of the sample under controlled laboratory conditions could be used to exactly identify which particular microorganism out of a targeted group has been rapidly detected in the field. It was also found that the personal sampler has a collection efficiency higher than 90% even for small-sized viruses (>20 nm) and stable performance over extended operating periods. In addition, it was found that for microorganisms used in this project (bacteriophages MS2 and T4) elimination of nucleic acids isolation and purification steps during sample preparation does not lead to the system sensitivity reduction, which is extremely

  6. Deciphering the code for retroviral integration target site selection.

    Directory of Open Access Journals (Sweden)

    Federico Andrea Santoni

    Full Text Available Upon cell invasion, retroviruses generate a DNA copy of their RNA genome and integrate retroviral cDNA within host chromosomal DNA. Integration occurs throughout the host cell genome, but target site selection is not random. Each subgroup of retrovirus is distinguished from the others by attraction to particular features on chromosomes. Despite extensive efforts to identify host factors that interact with retrovirion components or chromosome features predictive of integration, little is known about how integration sites are selected. We attempted to identify markers predictive of retroviral integration by exploiting Precision-Recall methods for extracting information from highly skewed datasets to derive robust and discriminating measures of association. ChIPSeq datasets for more than 60 factors were compared with 14 retroviral integration datasets. When compared with MLV, PERV or XMRV integration sites, strong association was observed with STAT1, acetylation of H3 and H4 at several positions, and methylation of H2AZ, H3K4, and K9. By combining peaks from ChIPSeq datasets, a supermarker was identified that localized within 2 kB of 75% of MLV proviruses and detected differences in integration preferences among different cell types. The supermarker predicted the likelihood of integration within specific chromosomal regions in a cell-type specific manner, yielding probabilities for integration into proto-oncogene LMO2 identical to experimentally determined values. The supermarker thus identifies chromosomal features highly favored for retroviral integration, provides clues to the mechanism by which retrovirus integration sites are selected, and offers a tool for predicting cell-type specific proto-oncogene activation by retroviruses.

  7. Level set method with automatic selective local statistics for brain tumor segmentation in MR images.

    Science.gov (United States)

    Thapaliya, Kiran; Pyun, Jae-Young; Park, Chun-Su; Kwon, Goo-Rak

    2013-01-01

    The level set approach is a powerful tool for segmenting images. This paper proposes a method for segmenting brain tumor images from MR images. A new signed pressure function (SPF) that can efficiently stop the contours at weak or blurred edges is introduced. The local statistics of the different objects present in the MR images were calculated. Using local statistics, the tumor objects were identified among different objects. In this level set method, the calculation of the parameters is a challenging task. The calculations of different parameters for different types of images were automatic. The basic thresholding value was updated and adjusted automatically for different MR images. This thresholding value was used to calculate the different parameters in the proposed algorithm. The proposed algorithm was tested on the magnetic resonance images of the brain for tumor segmentation and its performance was evaluated visually and quantitatively. Numerical experiments on some brain tumor images highlighted the efficiency and robustness of this method.

  8. Optical implementation of a feature-based neural network with application to automatic target recognition

    Science.gov (United States)

    Chao, Tien-Hsin; Stoner, William W.

    1993-01-01

    An optical neural network based on the neocognitron paradigm is introduced. A novel aspect of the architecture design is shift-invariant multichannel Fourier optical correlation within each processing layer. Multilayer processing is achieved by feeding back the ouput of the feature correlator interatively to the input spatial light modulator and by updating the Fourier filters. By training the neural net with characteristic features extracted from the target images, successful pattern recognition with intraclass fault tolerance and interclass discrimination is achieved. A detailed system description is provided. Experimental demonstrations of a two-layer neural network for space-object discrimination is also presented.

  9. A semi-automatic 2D-to-3D video conversion with adaptive key-frame selection

    Science.gov (United States)

    Ju, Kuanyu; Xiong, Hongkai

    2014-11-01

    To compensate the deficit of 3D content, 2D to 3D video conversion (2D-to-3D) has recently attracted more attention from both industrial and academic communities. The semi-automatic 2D-to-3D conversion which estimates corresponding depth of non-key-frames through key-frames is more desirable owing to its advantage of balancing labor cost and 3D effects. The location of key-frames plays a role on quality of depth propagation. This paper proposes a semi-automatic 2D-to-3D scheme with adaptive key-frame selection to keep temporal continuity more reliable and reduce the depth propagation errors caused by occlusion. The potential key-frames would be localized in terms of clustered color variation and motion intensity. The distance of key-frame interval is also taken into account to keep the accumulated propagation errors under control and guarantee minimal user interaction. Once their depth maps are aligned with user interaction, the non-key-frames depth maps would be automatically propagated by shifted bilateral filtering. Considering that depth of objects may change due to the objects motion or camera zoom in/out effect, a bi-directional depth propagation scheme is adopted where a non-key frame is interpolated from two adjacent key frames. The experimental results show that the proposed scheme has better performance than existing 2D-to-3D scheme with fixed key-frame interval.

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

    Directory of Open Access Journals (Sweden)

    Pedro J. Navarro

    2016-07-01

    Full Text Available 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.

  11. 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.

  12. Insights into the molecular basis of a bispecific antibody's target selectivity

    OpenAIRE

    Mazor, Yariv; Hansen, Anna; Yang, Chunning; Partha S Chowdhury; Wang, Jihong; Stephens, Geoffrey; Wu, Herren; Dall’Acqua, William F.

    2015-01-01

    Bispecific antibodies constitute a valuable class of therapeutics owing to their ability to bind 2 distinct targets. Dual targeting is thought to enhance biological efficacy, limit escape mechanisms, and increase target selectivity via a strong avidity effect mediated by concurrent binding to both antigens on the surface of the same cell. However, factors that regulate the extent of target selectivity are not well understood. We show that dual targeting alone is not sufficient to promote effi...

  13. Feature to space conversion during target selection in the dorsolateral and ventrolateral prefrontal cortex of monkeys.

    Science.gov (United States)

    Inoue, Masato; Mikami, Akichika

    2010-03-01

    To investigate the neuronal mechanism of the process of selection of a target from an array of stimuli, we analysed neuronal activity of the lateral prefrontal cortex during the response period of a serial probe reproduction task. During the response period of this task, monkeys were trained to select a memorized target object from an array of three objects and make a saccadic eye movement toward it. Of 611 neurons, 74 neurons showed visual response and 56 neurons showed presaccadic activity during the response period. Among visual neurons, 27 showed array- and target-selectivity. All of these array- and target-selective visual responses were recorded from the ventrolateral prefrontal cortex (VLPFC). Among 56 neurons with presaccadic activity, nine showed target-selective activity, 17 showed target- and direction-selective activity, and 23 showed direction-selective activity. The target-selective, and the target- and direction-selective activities were recorded from the VLPFC, and the direction-selective activities were recorded from VLPFC and dorsolateral prefrontal cortex (DLPFC). The starting time of the activity was earlier for the target-selective, and target- and direction-selective activities in VLPFC, intermediate for the direction-selective activities in VLPFC, and later for the direction-selective activities in DLPFC. These results suggest that VLPFC plays a role in the process of selection of a target object from an array of stimuli, VLPFC and DLPFC play a role in determining the location of the target in space, and DLPFC plays a role in selecting a direction and making a decision to generate a saccadic eye movement.

  14. A multispectral automatic target recognition application for maritime surveillance, search, and rescue

    Science.gov (United States)

    Schoonmaker, Jon; Reed, Scott; Podobna, Yuliya; Vazquez, Jose; Boucher, Cynthia

    2010-04-01

    Due to increased security concerns, the commitment to monitor and maintain security in the maritime environment is increasingly a priority. A country's coast is the most vulnerable area for the incursion of illegal immigrants, terrorists and contraband. This work illustrates the ability of a low-cost, light-weight, multi-spectral, multi-channel imaging system to handle the environment and see under difficult marine conditions. The system and its implemented detecting and tracking technologies should be organic to the maritime homeland security community for search and rescue, fisheries, defense, and law enforcement. It is tailored for airborne and ship based platforms to detect, track and monitor suspected objects (such as semi-submerged targets like marine mammals, vessels in distress, and drug smugglers). In this system, automated detection and tracking technology is used to detect, classify and localize potential threats or objects of interest within the imagery provided by the multi-spectral system. These algorithms process the sensor data in real time, thereby providing immediate feedback when features of interest have been detected. A supervised detection system based on Haar features and Cascade Classifiers is presented and results are provided on real data. The system is shown to be extendable and reusable for a variety of different applications.

  15. 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.

  16. 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…

  17. Target product selection - where can Molecular Pharming make the difference?

    Science.gov (United States)

    Paul, Mathew J; Teh, Audrey Y H; Twyman, Richard M; Ma, Julian K-C

    2013-01-01

    Four major developments have taken place in the world of Molecular Pharming recently. In the USA, the DARPA initiative challenged plant biotechnology companies to develop strategies for the large-scale manufacture of influenza vaccines, resulting in a successful Phase I clinical trial; in Europe the Pharma-Planta academic consortium gained regulatory approval for a plant-derived monoclonal antibody and completed a first-in-human phase I clinical trial; the Dutch pharmaceutical company Synthon acquired the assets of Biolex Therapeutics, an established Molecular Pharming company with several clinical candidates produced in their proprietary LEX system based on aquatic plants; and finally, the Israeli biotechnology company Protalix Biotherapeutics won FDA approval for the commercial release of a recombinant form of the enzyme glucocerebrosidase produced in carrot cells, the first plant biotechnology-derived biopharmaceutical in the world approved for the market. Commercial momentum is gathering pace with additional candidates now undergoing or awaiting approval for phase III clinical trials. Filling the product pipeline is vital to establish commercial sustainability, and the selection of appropriate target products for Molecular Pharming will be a critical factor. An interesting feature of the four stories outlined above is that they span the use of very different platform technologies addressing different types of molecules which aim to satisfy distinct market demands. In each case, Molecular Pharming was an economically and technically suitable approach, but this decisionmaking process is not necessarily straightforward. Although the various technologies available to Molecular Pharming are broad ranging and flexible, competing technologies are better established, so there needs to be a compelling reason to move into plants. It is most unlikely that plant biotechnology will be the answer for the whole biologics field. In this article, we discuss the current plant

  18. A human factors engineering approach to biomedical decision making: A new role for automatic target recognizer technologies

    Energy Technology Data Exchange (ETDEWEB)

    Sobel, A.L.; Stalker, K.T.; Yee, A.

    1995-01-01

    This report identifies the key features noted as requirements in the diagnostic decision-making process of Single Photon Emission Computed Tomography (SPECT) cardiac imaging. The report discusses the critical issues that create the basic system framework for design of an automatic target recognizer (ATR) algorithm prototype to support diagnosis of coronary artery disease. Candidate feature discovery algorithms that may form the basis of future work include Adaptive Resonance Theory and Bayesian Decision Network. A framework for the practitioner-Human-System-Interface would include baseline patient history and demographic data; reference cardiac imagery history; and current overlay imagery to provide complementary information (i.e., coronary angiography, echocardiography, and SPECT images). The goal is to design a prototype that would represent a fused present and historical {open_quotes}whole{close_quotes} functional, structural, and physiologic cardiac patient model. This framework decision-assisting platform would be available to practitioner and student alike, with no {open_quotes}real-world{close_quotes} consequences.

  19. Automatic selection of preprocessing methods for improving predictions on mass spectrometry protein profiles.

    Science.gov (United States)

    Pelikan, Richard C; Hauskrecht, Milos

    2010-11-13

    Mass spectrometry proteomic profiling has potential to be a useful clinical screening tool. One obstacle is providing a standardized method for preprocessing the noisy raw data. We have developed a system for automatically determining a set of preprocessing methods among several candidates. Our system's automated nature relieves the analyst of the need to be knowledgeable about which methods to use on any given dataset. Each stage of preprocessing is approached with many competing methods. We introduce metrics which are used to balance each method's attempts to correct noise versus preserving valuable discriminative information. We demonstrate the benefit of our preprocessing system on several SELDI and MALDI mass spectrometry datasets. Downstream classification is improved when using our system to preprocess the data.

  20. Selected problems of targeting active labour market policies in Poland

    OpenAIRE

    Monika Maria Maksim; Dominik Sliwicki

    2012-01-01

    Well targeted active labour market policies create better prospects for achieving higher net employment effects. This article attempts to analyse targeting of active labour market policies in the context of regulations contained in the Act of Employment Promotion and Labour Market Institutions, and current evaluation findings. The paper analyses basic active labour market policies, that have been in place in Poland in 2009. To assess program targeting logistic regression was applied.

  1. Development of Antibacterials Targeting the MEP Pathway of Select Agents

    Science.gov (United States)

    2014-05-01

    chemical class of antimicrobial drugs targeting MEP synthase. Additionally, our screening has highlighted a rationally designed bisubstrate inhibitor of...identify top compounds. • Mode of inhibition studies to determine the mechanism of action for the top hit compounds. • Identification of a...chemical class of antimicrobial drugs targeting MEP synthase. Additionally, our screening has highlighted a rationally designed bisubstrate inhibitor of

  2. Perceptual-Based Automatic Viewpoint Selection%基于感知的视点自动选取

    Institute of Scientific and Technical Information of China (English)

    潘斌; 王帅; 陈为; 彭群生

    2011-01-01

    为了在三维模型浏览系统中自动选取一个好的视点,使用户能够更有效地获取模型信息,提出一种自动视点选取算法.该算法基于视点信息熵理论和人眼的视觉感知理论,构建出一个与视点相关的模型视觉特征度量函数,并采用类随机梯度下降法来优化求解该目标函数,得到该度量标准下的最佳视点.实验结果证明,与已有算法相比,采用文中算法自动得到的最佳视点更符合人眼对于三维模型形状的心理感知,通过GPU加速,算法速度也大大提高.%By automatically selecting a good viewpoint in the 3Dvisualization systems, users can acquire information of the 3D models more effectively. Based on the theory of information entropy and human perception, this paper presents an algorithm for automatic viewpoint selection. Wedesign a perceptual feature function of the object with respect to all possible viewpoints. This function is then optimized by using a stochastic gradient descent like method. Experimental results show that our selected viewpoint provides a best view of the object which conforms very well with human perception.By using GPU, its time cost is also greatly reduced.

  3. 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....... This demonstrates that the cell model can be a useful tool for the design of effective lysosome-targeting drugs with minimal off-target interactions....

  4. 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.

  5. Systematic analysis of public domain compound potency data identifies selective molecular scaffolds across druggable target families.

    Science.gov (United States)

    Hu, Ye; Wassermann, Anne Mai; Lounkine, Eugen; Bajorath, Jürgen

    2010-01-28

    Molecular scaffolds that yield target family-selective compounds are of high interest in pharmaceutical research. There continues to be considerable debate in the field as to whether chemotypes with a priori selectivity for given target families and/or targets exist and how they might be identified. What do currently available data tell us? We present a systematic and comprehensive selectivity-centric analysis of public domain target-ligand interactions. More than 200 molecular scaffolds are identified in currently available active compounds that are selective for established target families. A subset of these scaffolds is found to produce compounds with high selectivity for individual targets among closely related ones. These scaffolds are currently underrepresented in approved drugs.

  6. Genome-wide polymorphisms show unexpected targets of natural selection

    OpenAIRE

    Pespeni, Melissa H.; Garfield, David A.; Manier, Mollie K; Palumbi, Stephen R.

    2011-01-01

    Natural selection can act on all the expressed genes of an individual, leaving signatures of genetic differentiation or diversity at many loci across the genome. New power to assay these genome-wide effects of selection comes from associating multi-locus patterns of polymorphism with gene expression and function. Here, we performed one of the first genome-wide surveys in a marine species, comparing purple sea urchins, Strongylocentrotus purpuratus, from two distant locations along the species...

  7. Enhanced tumor-targeting selectivity by modulating bispecific antibody binding affinity and format valence

    Science.gov (United States)

    Mazor, Yariv; Sachsenmeier, Kris F.; Yang, Chunning; Hansen, Anna; Filderman, Jessica; Mulgrew, Kathy; Wu, Herren; Dall’Acqua, William F.

    2017-01-01

    Bispecific antibodies are considered attractive bio-therapeutic agents owing to their ability to target two distinct disease mediators. Cross-arm avidity targeting of antigen double-positive cancer cells over single-positive normal tissue is believed to enhance the therapeutic efficacy, restrict major escape mechanisms and increase tumor-targeting selectivity, leading to reduced systemic toxicity and improved therapeutic index. However, the interplay of factors regulating target selectivity is not well understood and often overlooked when developing clinically relevant bispecific therapeutics. We show in vivo that dual targeting alone is not sufficient to endow selective tumor-targeting, and report the pivotal roles played by the affinity of the individual arms, overall avidity and format valence. Specifically, a series of monovalent and bivalent bispecific IgGs composed of the anti-HER2 trastuzumab moiety paired with affinity-modulated VH and VL regions of the anti-EGFR GA201 mAb were tested for selective targeting and eradication of double-positive human NCI-H358 non-small cell lung cancer target tumors over single-positive, non-target NCI-H358-HER2 CRISPR knock out tumors in nude mice bearing dual-flank tumor xenografts. Affinity-reduced monovalent bispecific variants, but not their bivalent bispecific counterparts, mediated a greater degree of tumor targeting selectivity, while the overall efficacy against the targeted tumor was not substantially affected. PMID:28067257

  8. Automatic endmember selection and nonlinear spectral unmixing of Lunar analog minerals

    Science.gov (United States)

    Rommel, Daniela; Grumpe, Arne; Felder, Marian Patrik; Wöhler, Christian; Mall, Urs; Kronz, Andreas

    2017-03-01

    While the interpretation of spectral reflectance data has been widely applied to detect the presence of minerals, determining and quantifying the abundances of minerals contained by planetary surfaces is still an open problem. With this paper we address one of the two main questions arising from the spectral unmixing problem. While the mathematical mixture model has been extensively researched, considerably less work has been committed to the selection of endmembers from a possibly huge database or catalog of potential endmembers. To solve the endmember selection problem we define a new spectral similarity measure that is not purely based on the reconstruction error, i.e. the squared difference between the modeled and the measured reflectance spectrum. To select reasonable endmembers, we extend the similarity measure by adding information extracted from the spectral absorption bands. This will allow for a better separation of spectrally similar minerals. Evaluating all possible subsets of a possibly very large catalog that contain at least one endmember leads to an exponential increase in computational complexity, rendering catalogs of 20-30 endmembers impractical. To overcome this computational limitation, we propose the usage of a genetic algorithm that, while initially starting with random subsets, forms new subsets by combining the best subsets and, to some extent, does a local search around the best subsets by randomly adding a few endmembers. A Monte-Carlo simulation based on synthetic mixtures and a catalog size varying from three to eight endmembers demonstrates that the genetic algorithm is expected to require less combinations to be evaluated than an exhaustive search if the catalog comprises 10 or more endmembers. Since the genetic algorithm evaluates some combinations multiple times, we propose a simple modification and store previously evaluated endmember combinations. The resulting algorithm is shown to never require more function evaluations than a

  9. Selection of DNA-encoded small molecule libraries against unmodified and non-immobilized protein targets.

    Science.gov (United States)

    Zhao, Peng; Chen, Zitian; Li, Yizhou; Sun, Dawei; Gao, Yuan; Huang, Yanyi; Li, Xiaoyu

    2014-09-15

    The selection of DNA-encoded libraries against biological targets has become an important discovery method in chemical biology and drug discovery, but the requirement of modified and immobilized targets remains a significant disadvantage. With a terminal protection strategy and ligand-induced photo-crosslinking, we show that iterated selections of DNA-encoded libraries can be realized with unmodified and non-immobilized protein targets.

  10. The ELG target selection with the BOSS survey

    CERN Document Server

    Escoffier, S; Ealet, A; Kneib, J -P; Zoubian, J; Lamareille, F

    2013-01-01

    The Baryon Acoustic Oscillation (BAO) feature in the power spectrum of galaxies can be used as a standard ruler to probe the accelerated expansion of the Universe. In this paper, we study several galaxy selection schemes aiming at building an emission-line galaxy (ELG) sample in the redshift range $0.6 < z < 1.7$, that would be suitable for future BAO studies using the Baryonic Oscillation Spectroscopic Survey (BOSS) spectrograph on the Sloan Digital Sky Survey (SDSS) telescope. We explore two different color selections using both the SDSS and the Canada-France-Hawaii Telescope Legacy Survey (CFHTLS) photometry in the $u, g, r, i$ bands and evaluate their performance for selecting bright ELG. This study confirms the feasibility of massive ELG surveys using the BOSS spectrographs on the SDSS telescope for a BAO detection at redshift $z\\sim1$, in particular for the proposed eBOSS experiment.

  11. 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...

  12. 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.

  13. 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.

  14. Automatic QSO Selection Using Machine Learning: Application on Massive Astronomical Database

    Science.gov (United States)

    Kim, D.-W.; Protopapas, P.; Alcock, C.; Byun, Y.-I.; Khardon, R.

    2011-07-01

    We present a new QSO (Quasi-Stellar Object) selection algorithm using Support Vector Machine (SVM), a supervised classification method, on a set of multiple extracted times series features such as period, amplitude, color, and autocorrelation value. We train a model that separates QSOs from variable stars, non-variable stars and microlensing events using the richest possible training set consisting of all known types of variables including QSOs from the MAssive Compact Halo Object (MACHO) database. We applied the trained model on the MACHO Large Magellanic Cloud (LMC) dataset, which consists of 40 million lightcurves, and found 1,620 QSO candidates. During the selection none of the 33,242 known MACHO variables were misclassified as QSO candidates. In order to estimate the true false positive rate, we crossmatched the candidates with astronomical catalogs including the Spitzer Surveying the Agents of a Galaxy's Evolution (SAGE) LMC catalog. The results further suggest that the majority of the candidates, more than 70%, are QSOs.

  15. Modeling charity donations: target selection, response time and gift size

    NARCIS (Netherlands)

    J-J. Jonker (Jedid-Jah); R. Paap (Richard); Ph.H.B.F. Franses (Philip Hans)

    2000-01-01

    textabstractCharitable organizations often consider direct mailings to raise donations. Obviously, it is important for a charity to make a profitable selection from available mailing lists, which can be its own list or a list obtained elsewhere. For this purpose, a charitable organization usually ha

  16. In vivo Target Residence Time and Kinetic Selectivity: The Association Rate Constant as Determinant.

    Science.gov (United States)

    de Witte, Wilhelmus E A; Danhof, Meindert; van der Graaf, Piet H; de Lange, Elizabeth C M

    2016-10-01

    It is generally accepted that, in conjunction with pharmacokinetics, the first-order rate constant of target dissociation is a major determinant of the time course and duration of in vivo target occupancy. Here we show that the second-order rate constant of target association can be equally important. On the basis of the commonly used mathematical models for drug-target binding, it is shown that a high target association rate constant can increase the (local) concentration of the drug, which decreases the rate of decline of target occupancy. The increased drug concentration can also lead to increased off-target binding and decreased selectivity. Therefore, the kinetics of both target association and dissociation need to be taken into account in the selection of drug candidates with optimal pharmacodynamic properties.

  17. Think Outside the Color-Box: Probabilistic Target Selection and the SDSS-XDQSO Quasar Targeting Catalog

    CERN Document Server

    Bovy, Jo; Hogg, David W; Myers, Adam D; Kirkpatrick, Jessica A; Schlegel, David J; Ross, Nicholas P; Sheldon, Erin S; McGreer, Ian D; Schneider, Donald P; Strauss, Michael A; Weaver, Benjamin A

    2010-01-01

    We present the SDSS-XDQSO quasar targeting catalog for efficient flux-based quasar target selection down to the faint limit of the SDSS catalog, even at medium redshifts (2.5 3.5) quasar probabilities for all 160,904,060 point-sources with dereddened i-band magnitude between 17.75 and 22.45 mag in the 14,555 deg^2 of imaging from SDSS Data Release 8. The catalog can be used to define a uniformly selected and efficient low- or medium-redshift quasar survey, such as that needed for the SDSS-III's Baryon Oscillation Spectroscopic Survey project. We show that the XDQSO technique performs as well as the current best photometric quasar selection technique at low redshift, and out-performs all other flux-based methods for selecting the medium-redshift quasars of our primary interest.

  18. Generic Prioritization Framework For Target Selection And Instrument Usage For Reconnaissance Mission Autonomy

    OpenAIRE

    Fink, Wolfgang

    2006-01-01

    A generic prioritization framework is introduced for addressing the problem of automated prioritization of target selection and instrument usage, applicable to Earth and Space reconnaissance missions. The framework is based on the assumptions that clustering of preliminary data for identified targets within an operational area has occurred and that the clustering quality can be expressed as an objective function. Target prioritization then means to rank targets accordi...

  19. Leveraging big data to transform target selection and drug discovery

    Science.gov (United States)

    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

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

    NARCIS (Netherlands)

    de Groote, Marloes L.; Verschure, Pernette J.; Rots, Marianne 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 D

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

    NARCIS (Netherlands)

    de Groote, M.L.; 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 D

  2. Follicular targeting--a promising tool in selective dermatotherapy.

    Science.gov (United States)

    Vogt, Annika; Mandt, Nathalie; Lademann, Juergen; Schaefer, Hans; Blume-Peytavi, Ulrike

    2005-12-01

    The penetration of topically applied compounds varies considerably in the different regions of the human body. The presence of hair follicles significantly contributes to this effect by an increase in surface area and a disruption of the epidermal barrier towards the lower parts of the hair follicle. The human hair follicle, hereby, serves not only as a reservoir, but also as a major entry point for topically applied compounds. Topical delivery of active compounds to specific targets within the skin may help reduce side-effects caused by unspecific reactions, and may help develop new strategies in the prevention and treatment of skin diseases. Various drug carrier and drug delivery systems are currently being investigated. The aim of these investigational efforts is to direct topically applied compounds to the different types of hair follicles and, ideally, to specific compartments and cell populations within the hair follicles. Follicular targeting offers opportunities for new developments, not only in hair therapy and in the treatment of hair follicle associated diseases but also in gene therapy and immunotherapy.

  3. Targeting of phage particles towards endothelial cells by antibodies selected through a multi-parameter selection strategy

    Science.gov (United States)

    Mandrup, Ole A.; Lykkemark, Simon; Kristensen, Peter

    2017-01-01

    One of the hallmarks of cancer is sustained angiogenesis. Here, normal endothelial cells are activated, and their formation of new blood vessels leads to continued tumour growth. An improved patient condition is often observed when angiogenesis is prevented or normalized through targeting of these genomically stable endothelial cells. However, intracellular targets constitute a challenge in therapy, as the agents modulating these targets have to be delivered and internalized specifically to the endothelial cells. Selection of antibodies binding specifically to certain cell types is well established. It is nonetheless a challenge to ensure that the binding of antibodies to the target cell will mediate internalization. Previously selection of such antibodies has been performed targeting cancer cell lines; most often using either monovalent display or polyvalent display. In this article, we describe selections that isolate internalizing antibodies by sequential combining monovalent and polyvalent display using two types of helper phages, one which increases display valence and one which reduces background. One of the selected antibodies was found to mediate internalization into human endothelial cells, although our results confirms that the single stranded nature of the DNA packaged into phage particles may limit applications aimed at targeting nucleic acids in mammalian cells. PMID:28186116

  4. BOAT: automatic alignment of biomedical ontologies using term informativeness and candidate selection.

    Science.gov (United States)

    Chua, Watson Wei Khong; Kim, Jung-Jae

    2012-04-01

    The biomedical sciences is one of the few domains where ontologies are widely being developed to facilitate information retrieval and knowledge sharing, but there still remains the problem that applications using different ontologies cannot share knowledge without explicit references between overlapping concepts. Ontology alignment is the task of identifying such equivalence relations between concepts across ontologies. Its application to the biomedical domain should address two open issues: (1) determining the equivalence of concept-pairs which have overlapping terms in their names, and (2) the high run-time required to align large ontologies which are typical in the biomedical domain. To address them, we present a novel approach, named the Biomedical Ontologies Alignment Technique (BOAT), which is state-of-the-art in terms of F-measure, precision and speed. A key feature of BOAT is that it considers the informativeness of each component word in the concept labels, which has significant impact on biomedical ontologies, resulting in a 12.2% increase in F-measure. Another important feature of BOAT is that it selects for comparison only concept pairs that show high likelihoods of equivalence, based on the similarity of their annotations. BOAT's F-measure of 0.88 for the alignment of the mouse and human anatomy ontologies is on par with that of another state-of-the-art matcher, AgreementMaker, while taking a shorter time.

  5. Rapid Automatic Motor Encoding of Competing Reach Options

    Directory of Open Access Journals (Sweden)

    Jason P. Gallivan

    2017-02-01

    Full Text Available Mounting neural evidence suggests that, in situations in which there are multiple potential targets for action, the brain prepares, in parallel, competing movements associated with these targets, prior to implementing one of them. Central to this interpretation is the idea that competing viewed targets, prior to selection, are rapidly and automatically transformed into corresponding motor representations. Here, by applying target-specific, gradual visuomotor rotations and dissociating, unbeknownst to participants, the visual direction of potential targets from the direction of the movements required to reach the same targets, we provide direct evidence for this provocative idea. Our results offer strong empirical support for theories suggesting that competing action options are automatically represented in terms of the movements required to attain them. The rapid motor encoding of potential targets may support the fast optimization of motor costs under conditions of target uncertainty and allow the motor system to inform decisions about target selection.

  6. Exploitation of Intra-Spectral Band Correlation for Rapid Feature Selection, and Target Identification in Hyperspectral Imagery

    Science.gov (United States)

    2009-03-01

    entitled “Improved Feature Extraction, Feature Selection, and Identification Techniques that Create a Fast Unsupervised Hyperspectral Target Detection...thesis proposal “Improved Feature Extraction, Feature Selection, and Identification Techniques that Create a Fast Unsupervised Hyperspectral Target...target or non-target classifications . Integration of this type of autonomous target detection algorithm along with hyperspectral imaging sensors

  7. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Directory of Open Access Journals (Sweden)

    John Koren

    Full Text Available MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB. Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  8. Rhodacyanine derivative selectively targets cancer cells and overcomes tamoxifen resistance.

    Science.gov (United States)

    Koren, John; Miyata, Yoshinari; Kiray, Janine; O'Leary, John C; Nguyen, Lana; Guo, Jianping; Blair, Laura J; Li, Xiaokai; Li, Xiokai; Jinwal, Umesh K; Cheng, Jin Q; Gestwicki, Jason E; Dickey, Chad A

    2012-01-01

    MKT-077, a rhodacyanine dye, was shown to produce cancer specific cell death. However, complications prevented the use of this compound beyond clinical trials. Here we describe YM-1, a derivative of MKT-077. We found that YM-1 was more cytotoxic and localized differently than MKT-077. YM-1 demonstrated this cytotoxicity across multiple cancer cell lines. This toxicity was limited to cancer cell lines; immortalized cell models were unaffected. Brief applications of YM-1 were found to be non-toxic. Brief treatment with YM-1 restored tamoxifen sensitivity to a refractory tamoxifen-resistant MCF7 cell model. This effect is potentially due to altered estrogen receptor alpha phosphorylation, an outcome precipitated by selective reductions in Akt levels (Akt/PKB). Thus, modifications to the rhodocyanine scaffold could potentially be made to improve efficacy and pharmacokinetic properties. Moreover, the impact on tamoxifen sensitivity could be a new utility for this compound family.

  9. 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

  10. Increasing intracellular bioavailable copper selectively targets prostate cancer cells.

    Science.gov (United States)

    Cater, Michael A; Pearson, Helen B; Wolyniec, Kamil; Klaver, Paul; Bilandzic, Maree; Paterson, Brett M; Bush, Ashley I; Humbert, Patrick O; La Fontaine, Sharon; Donnelly, Paul S; Haupt, Ygal

    2013-07-19

    The therapeutic efficacy of two bis(thiosemicarbazonato) copper complexes, glyoxalbis[N4-methylthiosemicarbazonato]Cu(II) [Cu(II)(gtsm)] and diacetylbis[N4-methylthiosemicarbazonato]Cu(II) [Cu(II)(atsm)], for the treatment of prostate cancer was assessed in cell culture and animal models. Distinctively, copper dissociates intracellularly from Cu(II)(gtsm) but is retained by Cu(II)(atsm). We further demonstrated that intracellular H2gtsm [reduced Cu(II)(gtsm)] continues to redistribute copper into a bioavailable (exchangeable) pool. Both Cu(II)(gtsm) and Cu(II)(atsm) selectively kill transformed (hyperplastic and carcinoma) prostate cell lines but, importantly, do not affect the viability of primary prostate epithelial cells. Increasing extracellular copper concentrations enhanced the therapeutic capacity of both Cu(II)(gtsm) and Cu(II)(atsm), and their ligands (H2gtsm and H2atsm) were toxic only toward cancerous prostate cells when combined with copper. Treatment of the Transgenic Adenocarcinoma of Mouse Prostate (TRAMP) model with Cu(II)(gtsm) (2.5 mg/kg) significantly reduced prostate cancer burden (∼70%) and severity (grade), while treatment with Cu(II)(atsm) (30 mg/kg) was ineffective at the given dose. However, Cu(II)(gtsm) caused mild kidney toxicity in the mice, associated primarily with interstitial nephritis and luminal distention. Mechanistically, we demonstrated that Cu(II)(gtsm) inhibits proteasomal chymotrypsin-like activity, a feature further established as being common to copper-ionophores that increase intracellular bioavailable copper. We have demonstrated that increasing intracellular bioavailable copper can selectively kill cancerous prostate cells in vitro and in vivo and have revealed the potential for bis(thiosemicarbazone) copper complexes to be developed as therapeutics for prostate cancer.

  11. Insights into the molecular basis of a bispecific antibody's target selectivity.

    Science.gov (United States)

    Mazor, Yariv; Hansen, Anna; Yang, Chunning; Chowdhury, Partha S; Wang, Jihong; Stephens, Geoffrey; Wu, Herren; Dall'Acqua, William F

    2015-01-01

    Bispecific antibodies constitute a valuable class of therapeutics owing to their ability to bind 2 distinct targets. Dual targeting is thought to enhance biological efficacy, limit escape mechanisms, and increase target selectivity via a strong avidity effect mediated by concurrent binding to both antigens on the surface of the same cell. However, factors that regulate the extent of target selectivity are not well understood. We show that dual targeting alone is not sufficient to promote efficient target selectivity, and report the substantial roles played by the affinity of the individual arms, overall avidity and valence. More particularly, various monovalent bispecific IgGs composed of an anti-CD70 moiety paired with variants of the anti-CD4 mAb ibalizumab were tested for preferential binding and selective depletion of CD4(+)/CD70(+) T cells over cells expressing only one of the target antigens that resulted from antibody dependent cell-mediated cytotoxicity. Variants exhibiting reduced CD4 affinity showed a greater degree of target selectivity, while the overall efficacy of the bispecific molecule was not affected.

  12. 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...

  13. Automatic spectral imaging protocol selection and iterative reconstruction in abdominal CT with reduced contrast agent dose: initial experience

    Energy Technology Data Exchange (ETDEWEB)

    Lv, Peijie; Liu, Jie; Chai, Yaru; Yan, Xiaopeng; Gao, Jianbo; Dong, Junqiang [The First Affiliated Hospital of Zhengzhou University, Department of Radiology, Zhengzhou, Henan Province (China)

    2017-01-15

    To evaluate the feasibility, image quality, and radiation dose of automatic spectral imaging protocol selection (ASIS) and adaptive statistical iterative reconstruction (ASIR) with reduced contrast agent dose in abdominal multiphase CT. One hundred and sixty patients were randomly divided into two scan protocols (n = 80) each; protocol A, 120 kVp/450 mgI/kg, filtered back projection algorithm (FBP); protocol B, spectral CT imaging with ASIS and 40 to 70 keV monochromatic images generated per 300 mgI/kg, ASIR algorithm. Quantitative parameters (image noise and contrast-to-noise ratios [CNRs]) and qualitative visual parameters (image noise, small structures, organ enhancement, and overall image quality) were compared. Monochromatic images at 50 keV and 60 keV provided similar or lower image noise, but higher contrast and overall image quality as compared with 120-kVp images. Despite the higher image noise, 40-keV images showed similar overall image quality compared to 120-kVp images. Radiation dose did not differ between the two protocols, while contrast agent dose in protocol B was reduced by 33 %. Application of ASIR and ASIS to monochromatic imaging from 40 to 60 keV allowed contrast agent dose reduction with adequate image quality and without increasing radiation dose compared to 120 kVp with FBP. (orig.)

  14. 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

  15. Candidate Targets for New Anti-Virulence Drugs: Selected Cases of Bacterial Adhesion and Biofilm Formation

    DEFF Research Database (Denmark)

    Klemm, Per; Hancock, Viktoria; Kvist, Malin;

    2007-01-01

    formation are highly attractive targets for new drugs. Specific adhesion provides bacteria with target selection and prevents removal by hydrodynamic flow forces. Bacterial adhesion is of paramount importance for bacterial pathogenesis. Adhesion is also the first step in biofilm formation. Biofilm formation...

  16. Auditory Stream Segregation Improves Infants' Selective Attention to Target Tones Amid Distracters

    Science.gov (United States)

    Smith, Nicholas A.; Trainor, Laurel J.

    2011-01-01

    This study examined the role of auditory stream segregation in the selective attention to target tones in infancy. Using a task adapted from Bregman and Rudnicky's 1975 study and implemented in a conditioned head-turn procedure, infant and adult listeners had to discriminate the temporal order of 2,200 and 2,400 Hz target tones presented alone,…

  17. Targeting MED1 LxxLL Motifs for Tissue-Selective Treatment of Human Breast Cancer

    Science.gov (United States)

    2012-09-01

    of a distinct band. Finally, we found that running a high percentage of agarose gel (3%) with high amount ethidium bromide provided relatively good...desired target, oligos that bind the non-desired target are often removed from the pool of aptamers through a process called “negative selection,” which

  18. 基于CS的SAR图像自动目标分割算法%Automatic Target Segmentation in SAR Images Using CS

    Institute of Scientific and Technical Information of China (English)

    杨萌; 张弓

    2011-01-01

    Object segmentation is an important step in SAR super-resolution processing and automatic target recognition. Considering image inherent sparse structures, an automatic target segmentation algorithm is proposed in this paper. First, a transformation matrix of dictionary is constructed to project the SAR image into a high dimensional space, and a sparse representation set of image local features is achieved. Second, a random sampling matrix is used to obtain its compression sampling and a mean-shift algorithm is applied to parallel process multiple sets of sample data. Finally, by using the sign test method, the SAR images data are classified as target pixels and background pixels classification. Experimental results demonstrate that the proposed algorithm has a good target segmentation results for hard target in synthetic aperture radar (SAR) images.%图像目标分割是SAR图像目标超分辨处理和自动目标识别的重要步骤.针对图像固有的稀疏结构,提出了一种SAR图像自动目标分割算法.通过构造变换字典将SAR图像数据投影到高维空间,实现了图像局部特征的稀疏表示,然后利用随机矩阵获得稀疏域局部特征的压缩采样,并对多组采样数据运用Mean-shift算法并行处理,最后通过符号检验法,实现了对目标像素与背景像素的分类.试验表明,该算法对硬目标具有较好的目标分割性能.

  19. 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.

  20. Determination of More Realistic Target 95% Values of Post Selection Delay in Modern Telephone Networks

    Directory of Open Access Journals (Sweden)

    V. Matić

    2012-04-01

    Full Text Available In this paper we present the telephone network and the recommendations, dealing with the greatest target values of Post Selection Delay. It is shown that the Post Selection Delay is the sum of the delays between the network nodes and that it has the smaller dispersion than the one, recommended as the greatest in the recommendations.

  1. Pro and cons of targeted selective treatment against digestive-tract strongyles of ruminants

    Directory of Open Access Journals (Sweden)

    Cabaret J.

    2008-09-01

    Full Text Available The increasing prevalence of resistance to anthelmintics among gastrointestinal nematodes and the desire for lower input agriculture have promoted the idea that targeted selective treatment (treating the animals in need of such a treatment and only them could be a sustainable solution for controlling internal parasites of ruminants. The pros are the slowing of resistance prevalence, lower residues of anthelmintics in meat and milk, and lower cost; the cons are the difficulty and time spent on selecting animals in need of treatment and the possibility of lower production. Using actual experiments and modelling we show that targeted selective treatment can be used to sustainably control gastrointestinal nematode infections in flock.

  2. Engineering of Targeted Nanoparticles for Cancer Therapy Using Internalizing Aptamers Isolated by Cell-Uptake Selection

    Science.gov (United States)

    Xiao, Zeyu; Levy-Nissenbaum, Etgar; Alexis, Frank; Lupták, Andrej; Teply, Benjamin A.; Chan, Juliana M.; Shi, Jinjun; Digga, Elise; Cheng, Judy; Langer, Robert; Farokhzad, Omid C.

    2012-01-01

    One of the major challenges in the development of targeted nanoparticles (NPs) for cancer therapy is to discover targeting ligands that allow for differential binding and uptake by the target cancer cells. Using prostate cancer (PCa) as a model disease, we developed a cell-uptake selection strategy to isolate PCa-specific internalizing 2'-Omethyl RNA aptamers (Apts) for NP incorporation. Twelve cycles of selection and counter-selection were done to obtain a panel of internalizing Apts, which can distinguish PCa cells from non-prostate and normal prostate cells. After Apt characterization, size minimization, and conjugation of the Apts with fluorescently-labeled polymeric NPs, the NP-Apt bioconjugates exhibit PCa specificity and enhancement in cellular uptake when compared to non-targeted NPs lacking the internalizing Apts. Furthermore, when docetaxel, a chemotherapeutic agent used for the treatment of PCa, was encapsulated within the NP-Apt, a significant improvement in cytotoxicity was achieved in targeted PCa cells. Rather than isolating high-affinity Apts as reported in previous selection processes, our selection strategy was designed to enrich cancer-cell specific internalizing Apts. A similar cell-uptake selection strategy may be used to develop specific internalizing ligands for a myriad of other diseases and can potentially facilitate delivering various molecules, including drugs and siRNAs, into cells. PMID:22214176

  3. Determination of target detection limits in hyperspectral data using band selection and dimensionality reduction

    Science.gov (United States)

    Gross, W.; Boehler, J.; Twizer, K.; Kedem, B.; Lenz, A.; Kneubuehler, M.; Wellig, P.; Oechslin, R.; Schilling, H.; Rotman, S.; Middelmann, W.

    2016-10-01

    Hyperspectral remote sensing data can be used for civil and military applications to robustly detect and classify target objects. High spectral resolution of hyperspectral data can compensate for the comparatively low spatial resolution, which allows for detection and classification of small targets, even below image resolution. Hyperspectral data sets are prone to considerable spectral redundancy, affecting and limiting data processing and algorithm performance. As a consequence, data reduction strategies become increasingly important, especially in view of near-real-time data analysis. The goal of this paper is to analyze different strategies for hyperspectral band selection algorithms and their effect on subpixel classification for different target and background materials. Airborne hyperspectral data is used in combination with linear target simulation procedures to create a representative amount of target-to-background ratios for evaluation of detection limits. Data from two different airborne hyperspectral sensors, AISA Eagle and Hawk, are used to evaluate transferability of band selection when using different sensors. The same target objects were recorded to compare the calculated detection limits. To determine subpixel classification results, pure pixels from the target materials are extracted and used to simulate mixed pixels with selected background materials. Target signatures are linearly combined with different background materials in varying ratios. The commonly used classification algorithms Adaptive Coherence Estimator (ACE) is used to compare the detection limit for the original data with several band selection and data reduction strategies. The evaluation of the classification results is done by assuming a fixed false alarm ratio and calculating the mean target-to-background ratio of correctly detected pixels. The results allow drawing conclusions about specific band combinations for certain target and background combinations. Additionally

  4. 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。

  5. Review of Radar Automatic Target Recognition%雷达目标识别技术综述

    Institute of Scientific and Technical Information of China (English)

    马林

    2011-01-01

    Radar target recognition technology is a complicated system which combines the sensor, target and environment etc. It is one of the important development area of modern radar technology. Current research status of target characteristics is summarized.Existing target recognition algorithms of different recognition objects are analyzed and summarized from ballistic missiles, air targets, targets on the sea surface and ground target. The development perspective of radar target recognition technology is also analyzed.%雷达目标识别技术是集传感器、目标、环境为一体的一项复杂的系统工程,是现代雷达技术的重要发展方向之一.文中总结了目标特性的研究现状,针对不同的识别对象,如弹道导弹、空中目标、海上目标和地面等目标,对现有的识别方法进行了梳理,并分析了雷达目标识别技术的发展方向.

  6. Transgenic gene knock-outs: functional genomics and therapeutic target selection.

    Science.gov (United States)

    Harris, S; Foord, S M

    2000-11-01

    The completion of the first draft of the human genome presents both a tremendous opportunity and enormous challenge to the pharmaceutical industry since the whole community, with few exceptions, will soon have access to the same pool of candidate gene sequences from which to select future therapeutic targets. The commercial imperative to select and pursue therapeutically relevant genes from within the overall content of the genome will be particularly intense for those gene families that currently represent the chemically tractable or 'drugable' gene targets. As a consequence the emphasis within exploratory research has shifted towards the evaluation and adoption of technology platforms that can add additional value to the gene selection process, either through functional studies or direct/indirect measures of disease alignment e.g., genetics, differential gene expression, proteomics, tissue distribution, comparative species data etc. The selection of biological targets for the development of potential new medicines relies, in part, on the quality of the in vivo biological data that correlates a particular molecular target with the underlying pathophysiology of a disease. Within the pharmaceutical industry, studies employing transgenic animals and, in particular, animals with specific gene deletions are playing an increasingly important role in the therapeutic target gene selection, drug candidate selection and product development phases of the overall drug discovery process. The potential of phenotypic information from gene knock-outs to contribute to a high-throughput target selection/validation strategy has hitherto been limited by the resources required to rapidly generate and characterise a large number of knock-out transgenics in a timely fashion. The offerings of several companies that provide an opportunity to overcome these hurdles, albeit at a cost, are assessed with respect to the strategic business needs of the pharmaceutical industry.

  7. Comparison of the cancer gene targeting and biochemical selectivities of all targeted kinase inhibitors approved for clinical use.

    Directory of Open Access Journals (Sweden)

    Joost C M Uitdehaag

    Full Text Available The anti-proliferative activities of all twenty-five targeted kinase inhibitor drugs that are in clinical use were measured in two large assay panels: (1 a panel of proliferation assays of forty-four human cancer cell lines from diverse tumour tissue origins; and (2 a panel of more than 300 kinase enzyme activity assays. This study provides a head-on comparison of all kinase inhibitor drugs in use (status Nov. 2013, and for six of these drugs, the first kinome profiling data in the public domain. Correlation of drug activities with cancer gene mutations revealed novel drug sensitivity markers, suggesting that cancers dependent on mutant CTNNB1 will respond to trametinib and other MEK inhibitors, and cancers dependent on SMAD4 to small molecule EGFR inhibitor drugs. Comparison of cellular targeting efficacies reveals the most targeted inhibitors for EGFR, ABL1 and BRAF(V600E-driven cell growth, and demonstrates that the best targeted agents combine high biochemical potency with good selectivity. For ABL1 inhibitors, we computationally deduce optimized kinase profiles for use in a next generation of drugs. Our study shows the power of combining biochemical and cellular profiling data in the evaluation of kinase inhibitor drug action.

  8. A cross validation study of deep brain stimulation targeting: from experts to atlas-based, segmentation-based and automatic registration algorithms.

    Science.gov (United States)

    Castro, F Javier Sanchez; Pollo, Claudio; Meuli, Reto; Maeder, Philippe; Cuisenaire, Olivier; Cuadra, Meritxell Bach; Villemure, Jean-Guy; Thiran, Jean-Philippe

    2006-11-01

    Validation of image registration algorithms is a difficult task and open-ended problem, usually application-dependent. In this paper, we focus on deep brain stimulation (DBS) targeting for the treatment of movement disorders like Parkinson's disease and essential tremor. DBS involves implantation of an electrode deep inside the brain to electrically stimulate specific areas shutting down the disease's symptoms. The subthalamic nucleus (STN) has turned out to be the optimal target for this kind of surgery. Unfortunately, the STN is in general not clearly distinguishable in common medical imaging modalities. Usual techniques to infer its location are the use of anatomical atlases and visible surrounding landmarks. Surgeons have to adjust the electrode intraoperatively using electrophysiological recordings and macrostimulation tests. We constructed a ground truth derived from specific patients whose STNs are clearly visible on magnetic resonance (MR) T2-weighted images. A patient is chosen as atlas both for the right and left sides. Then, by registering each patient with the atlas using different methods, several estimations of the STN location are obtained. Two studies are driven using our proposed validation scheme. First, a comparison between different atlas-based and nonrigid registration algorithms with a evaluation of their performance and usability to locate the STN automatically. Second, a study of which visible surrounding structures influence the STN location. The two studies are cross validated between them and against expert's variability. Using this scheme, we evaluated the expert's ability against the estimation error provided by the tested algorithms and we demonstrated that automatic STN targeting is possible and as accurate as the expert-driven techniques currently used. We also show which structures have to be taken into account to accurately estimate the STN location.

  9. A remotely controlled, semi-automatic target system for Rutherford backscattering spectrometry and elastic recoil detection analyses of polymeric membrane samples

    Energy Technology Data Exchange (ETDEWEB)

    Attayek, P.J. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States); Department of Biomedical Engineering, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7575 (United States); Meyer, E.S.; Lin, L. [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States); Rich, G.C.; Clegg, T.B. [Triangle Universities Nuclear Laboratory (TUNL), Durham, NC 27708-0308 (United States); Department of Physics and Astronomy, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-3255 (United States); Coronell, O., E-mail: coronell@unc.edu [Department of Environmental Sciences and Engineering, Gillings School of Global Public Health, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599-7431 (United States)

    2012-06-01

    A new target system for Rutherford backscattering spectrometry and elastic recoil detection analysis is described which enables remotely controlled, semi-automatic analysis of multiple organic polymer samples without exceeding damaging incident beam fluences. Control of fluence at a given beam current is achieved using two stepper motors to move a thin aluminum disk loaded with polymer samples both radially and azimuthally across the beam. Flexible beam spot locations and sample irradiation times are remotely controlled in two steps via two custom LabVIEW Trade-Mark-Sign programs. In the first step, a digital image of the target disk is converted into precise radial and azimuthal coordinates for each mounted polymer sample. In the second step, the motors implement the user-directed sample irradiation and fluence. Schematics of the target system hardware, a block diagram of interactions between the target system components, a description of routine procedures, and illustrative data taken with a 2 MeV {sup 4}He{sup 2+} analysis beam are provided.

  10. Contextual control over selective attention: evidence from a two-target method.

    Science.gov (United States)

    MacLellan, Ellen; Shore, David I; Milliken, Bruce

    2015-07-01

    Selective attention is generally studied with conflict tasks, using response time as the dependent measure. Here, we study the impact of selective attention to a first target, T1, presented simultaneously with a distractor, on the accuracy of subsequent encoding of a second target item, T2. This procedure produces an "attentional blink" (AB) effect much like that reported in other studies, and allowed us to study the influence of context on cognitive control with a novel method. In particular, we examined whether preparation to attend selectively to T1 had an impact on the selective encoding of T1 that would translate to report of T2. Preparation to attend selectively was manipulated by varying whether difficult selective attention T1 trials were presented in the context of other difficult selective attention T1 trials. The results revealed strong context effects of this nature, with smaller AB effects when difficult selective attention T1 trials were embedded in a context with many, rather than few, other difficult selective attention T1 trials. Further, the results suggest that both the trial-to-trial local context and the block-wide global context modulate performance in this task.

  11. An automatic fuzzy-based multi-temporal brain digital subtraction angiography image fusion algorithm using curvelet transform and content selection strategy.

    Science.gov (United States)

    Momeni, Saba; Pourghassem, Hossein

    2014-08-01

    Recently image fusion has prominent role in medical image processing and is useful to diagnose and treat many diseases. Digital subtraction angiography is one of the most applicable imaging to diagnose brain vascular diseases and radiosurgery of brain. This paper proposes an automatic fuzzy-based multi-temporal fusion algorithm for 2-D digital subtraction angiography images. In this algorithm, for blood vessel map extraction, the valuable frames of brain angiography video are automatically determined to form the digital subtraction angiography images based on a novel definition of vessel dispersion generated by injected contrast material. Our proposed fusion scheme contains different fusion methods for high and low frequency contents based on the coefficient characteristic of wrapping second generation of curvelet transform and a novel content selection strategy. Our proposed content selection strategy is defined based on sample correlation of the curvelet transform coefficients. In our proposed fuzzy-based fusion scheme, the selection of curvelet coefficients are optimized by applying weighted averaging and maximum selection rules for the high frequency coefficients. For low frequency coefficients, the maximum selection rule based on local energy criterion is applied to better visual perception. Our proposed fusion algorithm is evaluated on a perfect brain angiography image dataset consisting of one hundred 2-D internal carotid rotational angiography videos. The obtained results demonstrate the effectiveness and efficiency of our proposed fusion algorithm in comparison with common and basic fusion algorithms.

  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. 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.

  14. Topical liposome targeting of dyes, melanins, genes, and proteins selectively to hair follicles.

    Science.gov (United States)

    Hoffman, R M

    1998-01-01

    For therapeutic and cosmetic modification of hair, we have developed a hair-follicle-selective macromolecule and small molecule targeting system with topical application of phosphatidylcholine-based liposomes. Liposome-entrapped melanins, proteins, genes, and small-molecules have been selectively targeted to the hair follicle and hair shafts of mice. Liposomal delivery of these molecules is time dependent. Negligible amounts of delivered molecules enter the dermis, epidermis, or bloodstream thereby demonstrating selective follicle delivery. Naked molecules are trapped in the stratum corneum and are unable to enter the follicle. The potential of the hair-follicle liposome delivery system for therapeutic use for hair disease as well as for cosmesis has been demonstrated in 3-dimensional histoculture of hair-growing skin and mouse in vivo models. Topical liposome selective delivery to hair follicles has demonstrated the ability to color hair with melanin, the delivery of the active lac-Z gene to hair matrix cells and delivery of proteins as well. Liposome-targeting of molecules to hair follicles has also been achieved in human scalp in histoculture. Liposomes thus have high potential in selective hair follicle targeting of large and small molecules, including genes, opening the field of gene therapy and other molecular therapy of the hair process to restore hair growth, physiologically restore or alter hair pigment, and to prevent or accelerate hair loss.

  15. 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

    Gaze interaction affords hands-free control of computers. Pointing to and selecting small targets using gaze alone is difficult because of the limited accuracy of gaze pointing. This is the first experimental comparison of gaze-based interface tools for small-target (e.g. ... 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...

  16. 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

    2016-01-01

    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

  17. 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.

  18. Frontoparietal theta activity supports behavioral decisions in movement-target selection

    Directory of Open Access Journals (Sweden)

    Christian eRawle

    2012-05-01

    Full Text Available There is recent EEG evidence describing task-related changes of theta power in spatial attention and reaching/pointing tasks. Here, we aim to better characterize this theta activity and determine whether it is associated with visuospatial memory or with visuospatial selection functions of the frontoparietal cortex. We recorded EEG from 20 participants during a movement precuing task with centre-out joystick movements. Precues displayed 1, 2, or 4 potential targets and were followed (SOA 1.2 s by a central response cue indicating the movement target. Remembering the precued target location(s was mandatory in one and optional in a second version of the task. Analyses evaluated two slow brain potentials (CNV, contingent negative variation and CDA, contralateral delay activity and task-related power changes. Results showed a differential modulation of frontal CNV and parietal CDA, consistent with earlier described set-size effects on motor preparation and visual short-term memory. Short-lived phases of theta synchronization (ERS were found 150-500 ms after precue and response cue presentation, exhibiting parietal and frontal maxima. The increase of frontoparietal theta power following response cue presentation was strongly modulated by target load, i.e. absent for 1-target (when the movement target could be selected in advance, contrasting with a robust 20-50% ERS response in 2- and 4-target conditions. The scalp distribution, the timing, and the modulation by set-size suggest a role of theta activity in movement target selection. The results support a recently proposed view of theta as emerging around behavioral decision points, linked to the evaluation of choice-relevant information.

  19. Target Selection For The High Resolution Stereo Camera (hrsc) Experiment On Mars Express: Status Report

    Science.gov (United States)

    Hauber, E.; Neukum, G.; HRSC/Src Target Selection Team

    In order to facilitate effective operations planning and to maximize the science return of the HRSC/SRC experiment, we are currently preparing a global list of targets to be imaged during the ESA Mars Express mission. The target list is organized as a table, each line of which represents a single target. Each target is specified in terms of geographic location, imaging mode (i.e., the required selection of imaging param- eters like resolution, color filter, etc.), and the types of geologic processes which are of interest (e.g., aeolian, volcanic, fluvial). We also list the geologic unit(s) covered by each target as mapped in global geologic maps of Mars, as well as already existing imagery (Viking Orbiter, Mars Global Surveyor). In separate documents, the scientific rationale for imaging each target is comprehensively specified. Important findings of the MGS mission related to the targets are also described separately. In order to es- timate future data rates, we determine the areal size of each target and calculate the number of standard images and the data volume required to obtain an image mosaic of the entire target. In addition to the table, each target is graphically marked on a global, Viking-based base map (i.e., the MDIM-2 imaging model of the U.S.G.S.), allowing for quick visual inspection. These target maps will later be used during the planning stage of the mission: An interactive software tool has been developed which will use orbit and orientation parameters to plot the groundtrack of the spacecraft and the field of view of the camera onto the target maps. An operator checks whether the track crosses a target. It is straightforward, then, to determine the start and end times of imaging in order to cover the target. These times will be stored together with ad- ditional parameters (e.g., imaging mode, illumination conditions) for each orbit. The stored data will then be converted to commanding sequences. The target list is orga- nized according to the U

  20. Automatic ICD-10 multi-class classification of cause of death from plaintext autopsy reports through expert-driven feature selection

    Science.gov (United States)

    Mujtaba, Ghulam; Shuib, Liyana; Raj, Ram Gopal; Rajandram, Retnagowri; Shaikh, Khairunisa; Al-Garadi, Mohammed Ali

    2017-01-01

    Objectives Widespread implementation of electronic databases has improved the accessibility of plaintext clinical information for supplementary use. Numerous machine learning techniques, such as supervised machine learning approaches or ontology-based approaches, have been employed to obtain useful information from plaintext clinical data. This study proposes an automatic multi-class classification system to predict accident-related causes of death from plaintext autopsy reports through expert-driven feature selection with supervised automatic text classification decision models. Methods Accident-related autopsy reports were obtained from one of the largest hospital in Kuala Lumpur. These reports belong to nine different accident-related causes of death. Master feature vector was prepared by extracting features from the collected autopsy reports by using unigram with lexical categorization. This master feature vector was used to detect cause of death [according to internal classification of disease version 10 (ICD-10) classification system] through five automated feature selection schemes, proposed expert-driven approach, five subset sizes of features, and five machine learning classifiers. Model performance was evaluated using precisionM, recallM, F-measureM, accuracy, and area under ROC curve. Four baselines were used to compare the results with the proposed system. Results Random forest and J48 decision models parameterized using expert-driven feature selection yielded the highest evaluation measure approaching (85% to 90%) for most metrics by using a feature subset size of 30. The proposed system also showed approximately 14% to 16% improvement in the overall accuracy compared with the existing techniques and four baselines. Conclusion The proposed system is feasible and practical to use for automatic classification of ICD-10-related cause of death from autopsy reports. The proposed system assists pathologists to accurately and rapidly determine underlying

  1. W::Neo: a novel dual-selection marker for high efficiency gene targeting in Drosophila.

    Directory of Open Access Journals (Sweden)

    Wenke Zhou

    Full Text Available We have recently developed a so-called genomic engineering approach that allows for directed, efficient and versatile modifications of Drosophila genome by combining the homologous recombination (HR-based gene targeting with site-specific DNA integration. In genomic engineering and several similar approaches, a "founder" knock-out line must be generated first through HR-based gene targeting, which can still be a potentially time and resource intensive process. To significantly improve the efficiency and success rate of HR-based gene targeting in Drosophila, we have generated a new dual-selection marker termed W::Neo, which is a direct fusion between proteins of eye color marker White (W and neomycin resistance (Neo. In HR-based gene targeting experiments, mutants carrying W::Neo as the selection marker can be enriched as much as fifty times by taking advantage of the antibiotic selection in Drosophila larvae. We have successfully carried out three independent gene targeting experiments using the W::Neo to generate genomic engineering founder knock-out lines in Drosophila.

  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 APACHE POINT OBSERVATORY GALACTIC EVOLUTION EXPERIMENT (APOGEE)

    Energy Technology Data Exchange (ETDEWEB)

    Zasowski, G.; Johnson, Jennifer A.; Andrews, B.; Epstein, C. [Department of Astronomy, Ohio State University, Columbus, OH 43210 (United States); Frinchaboy, P. M.; Jackson, K. [Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX 76129 (United States); Majewski, S. R.; Chojnowski, S. D.; Skrutskie, M. F.; Beaton, R. L. [Department of Astronomy, University of Virginia, Charlottesville, VA 22904 (United States); Nidever, D. L. [Department of Astronomy, University of Michigan, Ann Arbor, MI 48109 (United States); Pinto, H. J. Rocha; Girardi, L. [Laboratorio Interinstitucional de e-Astronomia-LIneA, Rio de Janeiro, RJ 20921-400 (Brazil); Cudworth, K. M. [Yerkes Observatory, University of Chicago, Williams Bay, WI 53191 (United States); Munn, J. [US Naval Observatory, Flagstaff Station, Flagstaff, AZ 86001 (United States); Blake, C. H. [Department of Astrophysical Sciences, Princeton University, Princeton, NJ 08544 (United States); Covey, K. [Lowell Observatory, Flagstaff, AZ 86001 (United States); Deshpande, R.; Fleming, S. W. [Department of Astronomy and Astrophysics, Pennsylvania State University, University Park, PA 16802 (United States); Fabbian, D., E-mail: gail.zasowski@gmail.com [Instituto de Astrofisica de Canarias, Calle Via Lactea s/n, E-38205 La Laguna, Tenerife (Spain); and others

    2013-10-01

    The Apache Point Observatory Galactic Evolution Experiment (APOGEE) is a high-resolution infrared spectroscopic survey spanning all Galactic environments (i.e., bulge, disk, and halo), with the principal goal of constraining dynamical and chemical evolution models of the Milky Way. APOGEE takes advantage of the reduced effects of extinction at infrared wavelengths to observe the inner Galaxy and bulge at an unprecedented level of detail. The survey's broad spatial and wavelength coverage enables users of APOGEE data to address numerous Galactic structure and stellar populations issues. In this paper we describe the APOGEE targeting scheme and document its various target classes to provide the necessary background and reference information to analyze samples of APOGEE data with awareness of the imposed selection criteria and resulting sample properties. APOGEE's primary sample consists of {approx}10{sup 5} red giant stars, selected to minimize observational biases in age and metallicity. We present the methodology and considerations that drive the selection of this sample and evaluate the accuracy, efficiency, and caveats of the selection and sampling algorithms. We also describe additional target classes that contribute to the APOGEE sample, including numerous ancillary science programs, and we outline the targeting data that will be included in the public data releases.

  4. The feasibility of targeted selective gene therapy of the hair follicle.

    Science.gov (United States)

    Li, L; Hoffman, R M

    1995-07-01

    Loss of hair and hair colour is associated with ageing, and when it involves the scalp hair, it can be distressing to both sexes. Hair loss resulting from cancer chemotherapy is particularly distressing. However, safe, effective therapies directed to hair have only just started to be developed. The hair follicle is a complex skin appendage composed of epidermal and dermal tissue, with specialized keratinocytes, the hair matrix cells, forming the hair shaft. Specific therapy of the hair follicle depends on selective targeting of specific cells of the hair follicle. We have developed the histoculture of intact hair-growing skin on sponge-gel matrices. We have recently found in histocultured skin that liposomes can selectively target hair follicles to deliver both small and large molecules. That liposomes can target the hair follicle for delivery has been confirmed independently. Two decades ago we introduced the technique of entrapping DNA in liposomes for use in gene therapy. In this report we describe the selective targeting of the lacZ reporter gene to the hair follicles in mice after topical application of the gene entrapped in liposomes. These results demonstrate that highly selective, safe gene therapy for the hair process is feasible.

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

    Directory of Open Access Journals (Sweden)

    Marton Siklos

    2015-11-01

    Full Text Available 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 of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.

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

    Science.gov (United States)

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

    2015-11-01

    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 of cysteine proteases and their isozymes is problematic. This review provides a general update on strategies for cysteine protease inhibitor design and a focus on cathepsin B and calpain 1 as drug targets for neurodegenerative disorders; the latter focus providing an interesting query for the contemporary assumptions that irreversible, covalent protein modification and low selectivity are anathema to therapeutic safety and efficacy.

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

    DEFF Research Database (Denmark)

    Nielsen, Peter E

    2010-01-01

    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...... 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...... recognition considerably. Such modifications have also resulted in new approaches to targeted gene repair and sequence-selective double-strand cleavage of genomic DNA....

  8. 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.

  9. 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

  10. Auto-OBSD: Automatic parameter selection for reliable Oscillatory Behavior-based Signal Decomposition with an application to bearing fault signature extraction

    Science.gov (United States)

    Huang, Huan; Baddour, Natalie; Liang, Ming

    2017-03-01

    Bearing signals are often contaminated by in-band interferences and random noise. Oscillatory Behavior-based Signal Decomposition (OBSD) is a new technique which decomposes a signal according to its oscillatory behavior, rather than frequency or scale. Due to the low oscillatory transients of bearing fault-induced signals, the OBSD can be used to effectively extract bearing fault signatures from a blurred signal. However, the quality of the result highly relies on the selection of method-related parameters. Such parameters are often subjectively selected and a systematic approach has not been reported in the literature. As such, this paper proposes a systematic approach to automatic selection of OBSD parameters for reliable extraction of bearing fault signatures. The OBSD utilizes the idea of Morphological Component Analysis (MCA) that optimally projects the original signal to low oscillatory wavelets and high oscillatory wavelets established via the Tunable Q-factor Wavelet Transform (TQWT). In this paper, the effects of the selection of each parameter on the performance of the OBSD for bearing fault signature extraction are investigated. It is found that some method-related parameters can be fixed at certain values due to the nature of bearing fault-induced impulses. To adaptively tune the remaining parameters, index-guided parameter selection algorithms are proposed. A Convergence Index (CI) is proposed and a CI-guided self-tuning algorithm is developed to tune the convergence-related parameters, namely, penalty factor and number of iterations. Furthermore, a Smoothness Index (SI) is employed to measure the effectiveness of the extracted low oscillatory component (i.e. bearing fault signature). It is shown that a minimum SI implies an optimal result with respect to the adjustment of relevant parameters. Thus, two SI-guided automatic parameter selection algorithms are also developed to specify two other parameters, i.e., Q-factor of high-oscillatory wavelets and

  11. Digital curation: a proposal of a semi-automatic digital object selection-based model for digital curation in Big Data environments

    Directory of Open Access Journals (Sweden)

    Moisés Lima Dutra

    2016-08-01

    Full Text Available Introduction: This work presents a new approach for Digital Curations from a Big Data perspective. Objective: The objective is to propose techniques to digital curations for selecting and evaluating digital objects that take into account volume, velocity, variety, reality, and the value of the data collected from multiple knowledge domains. Methodology: This is an exploratory research of applied nature, which addresses the research problem in a qualitative way. Heuristics allow this semi-automatic process to be done either by human curators or by software agents. Results: As a result, it was proposed a model for searching, processing, evaluating and selecting digital objects to be processed by digital curations. Conclusions: It is possible to use Big Data environments as a source of information resources for Digital Curation; besides, Big Data techniques and tools can support the search and selection process of information resources by Digital Curations.

  12. Lepidopteran HMG-CoA reductase is a potential selective target for pest control

    Directory of Open Access Journals (Sweden)

    Yuan-mei Li

    2017-01-01

    Full Text Available As a consequence of the negative impacts on the environment of some insecticides, discovery of eco-friendly insecticides and target has received global attention in recent years. Sequence alignment and structural comparison of the rate-limiting enzyme HMG-CoA reductase (HMGR revealed differences between lepidopteran pests and other organisms, which suggested insect HMGR could be a selective insecticide target candidate. Inhibition of JH biosynthesis in vitro confirmed that HMGR inhibitors showed a potent lethal effect on the lepidopteran pest Manduca sexta, whereas there was little effect on JH biosynthesis in Apis mellifera and Diploptera punctata. The pest control application of these inhibitors demonstrated that they can be insecticide candidates with potent ovicidal activity, larvicidal activity and insect growth regulatory effects. The present study has validated that Lepidopteran HMGR can be a potent selective insecticide target, and the HMGR inhibitors (especially type II statins could be selective insecticide candidates and lead compounds. Furthermore, we demonstrated that sequence alignment, homology modeling and structural comparison may be useful for determining potential enzymes or receptors which can be eco-friendly pesticide  targets.

  13. Lepidopteran HMG-CoA reductase is a potential selective target for pest control

    Science.gov (United States)

    Li, Yuan-mei; Huang, Juan; Tobe, Stephen S.

    2017-01-01

    As a consequence of the negative impacts on the environment of some insecticides, discovery of eco-friendly insecticides and target has received global attention in recent years. Sequence alignment and structural comparison of the rate-limiting enzyme HMG-CoA reductase (HMGR) revealed differences between lepidopteran pests and other organisms, which suggested insect HMGR could be a selective insecticide target candidate. Inhibition of JH biosynthesis in vitro confirmed that HMGR inhibitors showed a potent lethal effect on the lepidopteran pest Manduca sexta, whereas there was little effect on JH biosynthesis in Apis mellifera and Diploptera punctata. The pest control application of these inhibitors demonstrated that they can be insecticide candidates with potent ovicidal activity, larvicidal activity and insect growth regulatory effects. The present study has validated that Lepidopteran HMGR can be a potent selective insecticide target, and the HMGR inhibitors (especially type II statins) could be selective insecticide candidates and lead compounds. Furthermore, we demonstrated that sequence alignment, homology modeling and structural comparison may be useful for determining potential enzymes or receptors which can be eco-friendly pesticide  targets. PMID:28133568

  14. 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.

  15. 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.

  16. Target Selection for the Apache Point Observatory Galactic Evolution Experiment (APOGEE)

    CERN Document Server

    Zasowski, G; Frinchaboy, P M; Majewski, S R; Nidever, D L; Pinto, H J Rocha; Girardi, L; Andrews, B; Chojnowski, S D; Cudworth, K M; Jackson, K; Munn, J; Skrutskie, M F; Beaton, R L; Blake, C H; Covey, K; Deshpande, R; Epstein, C; Fabbian, D; Fleming, S W; Hernandez, A Garcia; Herrero, A; Mahadevan, S; Meszaros, Sz; Schultheis, M; Sellgren, K; Terrien, R; van Saders, J; Prieto, C Allende; Bizyaev, D; Burton, A; Cunha, K; da Costa, L N; Hasselquist, S; Hearty, F; Holtzman, J; Perez, A E Garcia; Maia, M A G; O'Connell, R W; O'Donnell, C; Pinsonneault, M; Santiago, B X; Schiavon, R P; Shetrone, M; Smith, V; Wilson, J C

    2013-01-01

    The Apache Point Observatory Galactic Evolution Experiment (APOGEE) is a high-resolution infrared spectroscopic survey spanning all Galactic environments (i.e., bulge, disk, and halo), with the principal goal of constraining dynamical and chemical evolution models of the Milky Way. APOGEE takes advantage of the reduced effects of extinction at infrared wavelengths to observe the inner Galaxy and bulge at an unprecedented level of detail. The survey's broad spatial and wavelength coverage enables users of APOGEE data to address numerous Galactic structure and stellar populations issues. In this paper we describe the APOGEE targeting scheme and document its various target classes to provide the necessary background and reference information to analyze samples of APOGEE data with awareness of the imposed selection criteria and resulting sample properties. APOGEE's primary sample consists of ~100,000 red giant stars, selected to minimize observational biases in age and metallicity. We present the methodology and ...

  17. 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.

  18. Targeting MED1 LxxLL Motifs for Tissue-Selective Treatment of Human Breast Cancer

    Science.gov (United States)

    2014-09-01

    expression regulation (1). The latter can, in part, be attributed to small non-coding RNAs (sncRNAs) such as small interfering RNAs (siRNAs) and micro ...greatly limited their use. The objective of this study to isolate RNA aptamers that specifically target the estrogen receptor interacting NR boxes...for tissue-selective therapy. In this funding period, we have further tested and optimized the RNA aptamers obtained by SELEX method, based on its

  19. A mixture model with a reference-based automatic selection of components for disease classification from protein and/or gene expression levels

    Directory of Open Access Journals (Sweden)

    Kopriva Ivica

    2011-12-01

    Full Text Available Abstract Background Bioinformatics data analysis is often using linear mixture model representing samples as additive mixture of components. Properly constrained blind matrix factorization methods extract those components using mixture samples only. However, automatic selection of extracted components to be retained for classification analysis remains an open issue. Results The method proposed here is applied to well-studied protein and genomic datasets of ovarian, prostate and colon cancers to extract components for disease prediction. It achieves average sensitivities of: 96.2 (sd = 2.7%, 97.6% (sd = 2.8% and 90.8% (sd = 5.5% and average specificities of: 93.6% (sd = 4.1%, 99% (sd = 2.2% and 79.4% (sd = 9.8% in 100 independent two-fold cross-validations. Conclusions We propose an additive mixture model of a sample for feature extraction using, in principle, sparseness constrained factorization on a sample-by-sample basis. As opposed to that, existing methods factorize complete dataset simultaneously. The sample model is composed of a reference sample representing control and/or case (disease groups and a test sample. Each sample is decomposed into two or more components that are selected automatically (without using label information as control specific, case specific and not differentially expressed (neutral. The number of components is determined by cross-validation. Automatic assignment of features (m/z ratios or genes to particular component is based on thresholds estimated from each sample directly. Due to the locality of decomposition, the strength of the expression of each feature across the samples can vary. Yet, they will still be allocated to the related disease and/or control specific component. Since label information is not used in the selection process, case and control specific components can be used for classification. That is not the case with standard factorization methods. Moreover, the component selected by proposed method

  20. Targeted proteomics by selected reaction monitoring mass spectrometry: applications to systems biology and biomarker discovery.

    Science.gov (United States)

    Elschenbroich, Sarah; Kislinger, Thomas

    2011-02-01

    Mass Spectrometry-based proteomics is now considered a relatively established strategy for protein analysis, ranging from global expression profiling to the identification of protein complexes and specific post-translational modifications. Recently, Selected Reaction Monitoring Mass Spectrometry (SRM-MS) has become increasingly popular in proteome research for the targeted quantification of proteins and post-translational modifications. Using triple quadrupole instrumentation (QqQ), specific analyte molecules are targeted in a data-directed mode. Used routinely for the quantitative analysis of small molecular compounds for at least three decades, the technology is now experiencing broadened application in the proteomics community. In the current review, we will provide a detailed summary of current developments in targeted proteomics, including some of the recent applications to biological research and biomarker discovery.

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

    Science.gov (United States)

    Dugal, Cherie J; van Beest, Floris M; Vander Wal, Eric; Brook, Ryan K

    2013-10-01

    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, in southwestern Manitoba, Canada. Distance to protected area was the most important covariate influencing resource selection and hunter-kill sites of elk (AICw = 1.00). Collared adult males (which are most likely to be infected with bovine tuberculosis (Mycobacterium bovis) and chronic wasting 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-kill sites of these cohorts were positively associated with landscape-level forest cover and increasing distance to streams and negatively associated with high road density. Local-level forest was positively associated with collared animal locations and hunter-kill sites; however, selection was stronger for collared juvenile males and hunter-killed adult females. In instances where disease infects a metapopulation and eradication is infeasible, a principle goal of management is to limit the spread of disease among infected animals. We map high-risk areas that are regularly used by potentially infectious hosts but currently underrepresented in the distribution of kill sites. We present a novel application of widely available data to target hunter distribution based on host resource

  2. 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.

  3. A Peptidomimetic Antibiotic Targets Outer Membrane Proteins and Disrupts Selectively the Outer Membrane in Escherichia coli.

    Science.gov (United States)

    Urfer, Matthias; Bogdanovic, Jasmina; Lo Monte, Fabio; Moehle, Kerstin; Zerbe, Katja; Omasits, Ulrich; Ahrens, Christian H; Pessi, Gabriella; Eberl, Leo; Robinson, John A

    2016-01-22

    Increasing antibacterial resistance presents a major challenge in antibiotic discovery. One attractive target in Gram-negative bacteria is the unique asymmetric outer membrane (OM), which acts as a permeability barrier that protects the cell from external stresses, such as the presence of antibiotics. We describe a novel β-hairpin macrocyclic peptide JB-95 with potent antimicrobial activity against Escherichia coli. This peptide exhibits no cellular lytic activity, but electron microscopy and fluorescence studies reveal an ability to selectively disrupt the OM but not the inner membrane of E. coli. The selective targeting of the OM probably occurs through interactions of JB-95 with selected β-barrel OM proteins, including BamA and LptD as shown by photolabeling experiments. Membrane proteomic studies reveal rapid depletion of many β-barrel OM proteins from JB-95-treated E. coli, consistent with induction of a membrane stress response and/or direct inhibition of the Bam folding machine. The results suggest that lethal disruption of the OM by JB-95 occurs through a novel mechanism of action at key interaction sites within clusters of β-barrel proteins in the OM. These findings open new avenues for developing antibiotics that specifically target β-barrel proteins and the integrity of the Gram-negative OM.

  4. Risk-targeted selection of agricultural holdings for post-epidemic surveillance: estimation of efficiency gains.

    Directory of Open Access Journals (Sweden)

    Ian G Handel

    Full Text Available Current post-epidemic sero-surveillance uses random selection of animal holdings. A better strategy may be to estimate the benefits gained by sampling each farm and use this to target selection. In this study we estimate the probability of undiscovered infection for sheep farms in Devon after the 2001 foot-and-mouth disease outbreak using the combination of a previously published model of daily infection risk and a simple model of probability of discovery of infection during the outbreak. This allows comparison of the system sensitivity (ability to detect infection in the area of arbitrary, random sampling compared to risk-targeted selection across a full range of sampling budgets. We show that it is possible to achieve 95% system sensitivity by sampling, on average, 945 farms with random sampling and 184 farms with risk-targeted sampling. We also examine the effect of ordering samples by risk to expedite return to a disease-free status. Risk ordering the sampling process results in detection of positive farms, if present, 15.6 days sooner than with randomly ordered sampling, assuming 50 farms are tested per day.

  5. 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.

  6. 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

  7. Selective Targeting of Extracellular Insulin-Degrading Enzyme by Quasi-Irreversible Thiol-Modifying Inhibitors.

    Science.gov (United States)

    Abdul-Hay, Samer O; Bannister, Thomas D; Wang, Hui; Cameron, Michael D; Caulfield, Thomas R; Masson, Amandine; Bertrand, Juliette; Howard, Erin A; McGuire, Michael P; Crisafulli, Umberto; Rosenberry, Terrone R; Topper, Caitlyn L; Thompson, Caroline R; Schürer, Stephan C; Madoux, Franck; Hodder, Peter; Leissring, Malcolm A

    2015-12-18

    Many therapeutically important enzymes are present in multiple cellular compartments, where they can carry out markedly different functions; thus, there is a need for pharmacological strategies to selectively manipulate distinct pools of target enzymes. Insulin-degrading enzyme (IDE) is a thiol-sensitive zinc-metallopeptidase that hydrolyzes diverse peptide substrates in both the cytosol and the extracellular space, but current genetic and pharmacological approaches are incapable of selectively inhibiting the protease in specific subcellular compartments. Here, we describe the discovery, characterization, and kinetics-based optimization of potent benzoisothiazolone-based inhibitors that, by virtue of a unique quasi-irreversible mode of inhibition, exclusively inhibit extracellular IDE. The mechanism of inhibition involves nucleophilic attack by a specific active-site thiol of the enzyme on the inhibitors, which bear an isothiazolone ring that undergoes irreversible ring opening with the formation of a disulfide bond. Notably, binding of the inhibitors is reversible under reducing conditions, thus restricting inhibition to IDE present in the extracellular space. The identified inhibitors are highly potent (IC50(app) = 63 nM), nontoxic at concentrations up to 100 μM, and appear to preferentially target a specific cysteine residue within IDE. These novel inhibitors represent powerful new tools for clarifying the physiological and pathophysiological roles of this poorly understood protease, and their unusual mechanism of action should be applicable to other therapeutic targets.

  8. Selective innervation of foreign muscles following damage or removal of normal muscle targets.

    Science.gov (United States)

    Boss, V; Wigston, D J

    1992-08-22

    The restoration of a normal pattern of neural connectivity following nerve injury depends upon the selective reinnervation of appropriate postsynaptic targets. Previous studies suggest that, in the neuromuscular system, recognition between regenerating motoneurons and target muscles depends upon the positions of origin of the motoneurons and muscles. In axolotls, portions of the motor pools of adjacent muscles overlap. We found that, following removal of a pair of adjacent hindlimb muscles, anterior and posterior iliotibialis, many regenerating iliotibialis motor axons invaded foreign muscles. A more anterior foreign muscle, puboischiofemoralis internus, received greater innervation from anterior iliotibialis motoneurons, whereas a more posterior muscle, iliofibularis, received greater innervation from posterior iliotibialis motoneurons. Furthermore, anterior iliotibialis motoneurons that reinnervated puboischiofemoralis internus occupied the rostral portion of anterior iliotibialis motor pool, which overlaps that of puboischiofemoralis internus. Anterior iliotibialis motoneurons that reinnervated iliofibularis occupied the caudal portion of the anterior iliotibialis motor pool, which overlaps that of iliofibularis. When both anterior and posterior iliotibialis were damaged so that their myofibers were permanently destroyed, the rostrocaudal origins of the motoneurons that reinnervated them were virtually the same, suggesting that the motoneurons had difficulty distinguishing between the myofiberless iliotibialis muscles. However, some iliotibialis motoneurons invaded puboischiofemoralis internus instead of their myofiberless targets. Puboischiofemoralis internus received more innervation from the anterior iliotibialis motoneurons than the positionally less appropriate posterior iliotibialis motoneurons. These data are consistent with the hypothesis that selective reinnervation of muscle depends upon a system of recognition cues based on position.

  9. Using image processing technology and mathematical algorithm in the automatic selection of vocal cord opening and closing images from the larynx endoscopy video.

    Science.gov (United States)

    Kuo, Chung-Feng Jeffrey; Chu, Yueng-Hsiang; Wang, Po-Chun; Lai, Chun-Yu; Chu, Wen-Lin; Leu, Yi-Shing; Wang, Hsing-Won

    2013-12-01

    The human larynx is an important organ for voice production and respiratory mechanisms. The vocal cord is approximated for voice production and open for breathing. The videolaryngoscope is widely used for vocal cord examination. At present, physicians usually diagnose vocal cord diseases by manually selecting the image of the vocal cord opening to the largest extent (abduction), thus maximally exposing the vocal cord lesion. On the other hand, the severity of diseases such as vocal palsy, atrophic vocal cord is largely dependent on the vocal cord closing to the smallest extent (adduction). Therefore, diseases can be assessed by the image of the vocal cord opening to the largest extent, and the seriousness of breathy voice is closely correlated to the gap between vocal cords when closing to the smallest extent. The aim of the study was to design an automatic vocal cord image selection system to improve the conventional selection process by physicians and enhance diagnosis efficiency. Also, due to the unwanted fuzzy images resulting from examination process caused by human factors as well as the non-vocal cord images, texture analysis is added in this study to measure image entropy to establish a screening and elimination system to effectively enhance the accuracy of selecting the image of the vocal cord closing to the smallest extent.

  10. 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...

  11. 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.

  12. Evodiamine selectively targets cancer stem-like cells through the p53-p21-Rb pathway.

    Science.gov (United States)

    Han, Seula; Woo, Jong Kyu; Jung, Yuchae; Jeong, Dawoon; Kang, Minsook; Yoo, Young-Ji; Lee, Hani; Oh, Seung Hyun; Ryu, Jae-Ha; Kim, Woo-Young

    2016-01-22

    In spite of the recent improvements, the resistance to chemotherapy/radiotherapy followed by relapse is the main hurdle for the successful treatment of breast cancer, a leading cause of death in women. A small population of breast cancer cells that have stem-like characteristics (cancer stem-like cells; CSLC) may contribute to this resistance and relapse. Here, we report on a component of a traditional Chinese medicine, evodiamine, which selectively targets CSLC of breast cancer cell lines MCF7 and MDAMB 231 at a concentration that does show a little or no cytotoxic effect on bulk cancer cells. While evodiamine caused the accumulation of bulk cancer cells at the G2/M phase, it did not hold CSLC in a specific cell cycle phase but instead, selectively killed CSLC. This was not due to the culture of CSLC in suspension or without FBS. A proteomic analysis and western blotting revealed that evodiamine changed the expression of cell cycle regulating molecules more efficiently in CSLC cells than in bulk cancer cells. Surprisingly, evodiamine selectively activated p53 and p21 and decreased inactive Rb, the master molecules in G1/S checkpoint. These data collectively suggest a novel mechanism involving CSLC-specific targeting by evodiamine and its possible use to the therapy of breast cancer.

  13. Aurora B kinase is a potent and selective target in MYCN-driven neuroblastoma.

    Science.gov (United States)

    Bogen, Dominik; Wei, Jun S; Azorsa, David O; Ormanoglu, Pinar; Buehler, Eugen; Guha, Rajarshi; Keller, Jonathan M; Mathews Griner, Lesley A; Ferrer, Marc; Song, Young K; Liao, Hongling; Mendoza, Arnulfo; Gryder, Berkley E; Sindri, Sivasish; He, Jianbin; Wen, Xinyu; Zhang, Shile; Shern, John F; Yohe, Marielle E; Taschner-Mandl, Sabine; Shohet, Jason M; Thomas, Craig J; Martin, Scott E; Ambros, Peter F; Khan, Javed

    2015-11-01

    Despite advances in multimodal treatment, neuroblastoma (NB) is often fatal for children with high-risk disease and many survivors need to cope with long-term side effects from high-dose chemotherapy and radiation. To identify new therapeutic targets, we performed an siRNA screen of the druggable genome combined with a small molecule screen of 465 compounds targeting 39 different mechanisms of actions in four NB cell lines. We identified 58 genes as targets, including AURKB, in at least one cell line. In the drug screen, aurora kinase inhibitors (nine molecules) and in particular the AURKB-selective compound, barasertib, were the most discriminatory with regard to sensitivity for MYCN-amplified cell lines. In an expanded panel of ten NB cell lines, those with MYCN-amplification and wild-type TP53 were the most sensitive to low nanomolar concentrations of barasertib. Inhibition of the AURKB kinase activity resulted in decreased phosphorylation of the known target, histone H3, and upregulation of TP53 in MYCN-amplified, TP53 wild-type cells. However, both wild-type and TP53 mutant MYCN-amplified cell lines arrested in G2/M phase upon AURKB inhibition. Additionally, barasertib induced endoreduplication and apoptosis. Treatment of MYCN-amplified/TP53 wild-type neuroblastoma xenografts resulted in profound growth inhibition and tumor regression. Therefore, aurora B kinase inhibition is highly effective in aggressive neuroblastoma and warrants further investigation in clinical trials.

  14. Selective cellular uptake and induction of apoptosis of cancer-targeted selenium nanoparticles.

    Science.gov (United States)

    Huang, Yanyu; He, Lizhen; Liu, Wen; Fan, Cundong; Zheng, Wenjie; Wong, Yum-Shing; Chen, Tianfeng

    2013-09-01

    Selenium nanoparticles (SeNPs) have garnered a great deal of attention as potential cancer therapeutic payloads. However, the in vivo targeting drug delivery has been challenging. Herein, we describe the synthesis of tansferrin (Tf)-conjugated SeNPs and its use as a cancer-targeted drug delivery system to achieve enhanced cellular uptake and anticancer efficacy. Tf as targeting ligand significantly enhances the cellular uptake of doxorubicin (DOX)-loaded SeNPs through clathrin-mediated and caveolae/lipid raft-mediated endocytosis in cancer cells overexpressing transferrin receptor, and increases their selectivity between cancer and normal cells. DOX-loaded and Tf-conjugated SeNPs (Tf-SeNPs) exhibits unprecedented enhanced cytotoxicity toward cancer cells through induction of apoptosis with the involvement of intrinsic and extrinsic pathways. Internalized Tf-SeNPs triggers intracellular ROS overproduction, thus activates p53 and MAPKs pathways to promote cell apoptosis. In the nude mice xenograft experiment, Tf-SeNPs significantly inhibits the tumor growth via induction of p53-mediated apoptosis. This cancer-targeted design of SeNPs opens a new path for synergistic treating of cancer with higher efficacy and decreased side effects.

  15. Selection of target mutation in rat gastrointestinal tract E. coli by minute dosage of enrofloxacin.

    Science.gov (United States)

    Lin, Dachuan; Chen, Kaichao; Li, Ruichao; Liu, Lizhang; Guo, Jiubiao; Yao, Wen; Chen, Sheng

    2014-01-01

    It has been suggested that bacterial resistance is selected within a mutation selection window of antibiotics. More recent studies showed that even extremely low concentration of antibiotic could select resistant bacteria in vitro. Yet little is known about the exact antibiotic concentration range that can effectively select for resistant organisms in animal gastrointestinal (GI) tract. In this study, the effect of different dosages of enrofloxacin on resistance and mutation development in rat GI tract E. coli was investigated by determining the number of resistant E. coli recoverable from rat fecal samples. Our data showed that high dose antibiotic treatment could effectively eliminate E. coli with single gyrA mutation in the early course of treatment, yet the eradication effects diminished upon prolonged treatment. Therapeutic and sub-therapeutic dose (1/10 and 1/100 of therapeutic doses) of enrofloxacin could effectively select for mutation in GI tract E. coli at the later course of enrofloxacin treatment and during the cessation periods. Surprisingly, very low dose of enrofloxacin (1/1000 therapeutic dose) could also select for mutation in GI tract E. coli at the later course of enrofloxacin treatment, only with slightly lower efficiency. No enrofloxacin-resistant E. coli could be selected at all test levels of enrofloxacin during long term treatment and the strength of antibiotic treatment does not alter the overall level of E. coli in rat GI tract. This study demonstrated that long term antibiotic treatment seems to be the major trigger for the development of target mutations in GI tract E. coli, which provided insight into the rational use of antibiotics in animal husbandry.

  16. 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.

  17. Margin selection to compensate for loss of target dose coverage due to target motion during external-beam radiation therapy of the lung.

    Science.gov (United States)

    Foster, W Kyle; Osei, Ernest; Barnett, Rob

    2015-01-08

    The aim of this study is to provide guidelines for the selection of external-beam radiation therapy target margins to compensate for target motion in the lung during treatment planning. A convolution model was employed to predict the effect of target motion on the delivered dose distribution. The accuracy of the model was confirmed with radiochromic film measurements in both static and dynamic phantom modes. 502 unique patient breathing traces were recorded and used to simulate the effect of target motion on a dose distribution. A 1D probability density function (PDF) representing the position of the target throughout the breathing cycle was generated from each breathing trace obtained during 4D CT. Changes in the target D95 (the minimum dose received by 95% of the treatment target) due to target motion were analyzed and shown to correlate with the standard deviation of the PDF. Furthermore, the amount of target D95 recovered per millimeter of increased field width was also shown to correlate with the standard deviation of the PDF. The sensitivity of changes in dose coverage with respect to target size was also determined. Margin selection recommendations that can be used to compensate for loss of target D95 were generated based on the simulation results. These results are discussed in the context of clinical plans. We conclude that, for PDF standard deviations less than 0.4 cm with target sizes greater than 5 cm, little or no additional margins are required. Targets which are smaller than 5 cm with PDF standard deviations larger than 0.4 cm are most susceptible to loss of coverage. The largest additional required margin in this study was determined to be 8 mm.

  18. Target selection and pharma industry productivity: what can we learn from technology S-curve theory?

    Science.gov (United States)

    Brown, David

    2006-07-01

    The number of new drug approvals per annum has been decreasing regularly over the past decade, and changes made 12 to 15 years ago to the research and development approach of the pharmaceutical industry may have contributed to this fall in productivity. In particular, the rapid switch at that time away from an 'observation-led' approach toward a 'hypothesis-led' approach to target selection may be a key contributing factor to this issue. The strengths and weaknesses of both approaches are analyzed herein, and it is suggested that unsolved weaknesses in both approaches are holding back the productivity of the pharmaceutical/biotechnology industry.

  19. The Gaia Survey Contribution to EChO Target Selection and Characterization

    CERN Document Server

    Sozzetti, A

    2014-01-01

    The scientific output of the proposed EChO mission (in terms of spectroscopic characterization of the atmospheres of transiting extrasolar planets) will be maximized by a careful selection of targets and by a detailed characterization of the main physical parameters (such as masses and radii) of both the planets and their stellar hosts. To achieve this aim, the availability of high-quality data from other space-borne and ground-based programs will play a crucial role. Here we identify and discuss the elements of the Gaia catalogue that will be of utmost relevance for the selection and characterization of transiting planet systems to be observed by the proposed EChO mission.

  20. 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.

  1. The selective processing of emotional visual stimuli while detecting auditory targets: an ERP analysis.

    Science.gov (United States)

    Schupp, Harald T; Stockburger, Jessica; Bublatzky, Florian; Junghöfer, Markus; Weike, Almut I; Hamm, Alfons O

    2008-09-16

    Event-related potential studies revealed an early posterior negativity (EPN) for emotional compared to neutral pictures. Exploring the emotion-attention relationship, a previous study observed that a primary visual discrimination task interfered with the emotional modulation of the EPN component. To specify the locus of interference, the present study assessed the fate of selective visual emotion processing while attention is directed towards the auditory modality. While simply viewing a rapid and continuous stream of pleasant, neutral, and unpleasant pictures in one experimental condition, processing demands of a concurrent auditory target discrimination task were systematically varied in three further experimental conditions. Participants successfully performed the auditory task as revealed by behavioral performance and selected event-related potential components. Replicating previous results, emotional pictures were associated with a larger posterior negativity compared to neutral pictures. Of main interest, increasing demands of the auditory task did not modulate the selective processing of emotional visual stimuli. With regard to the locus of interference, selective emotion processing as indexed by the EPN does not seem to reflect shared processing resources of visual and auditory modality.

  2. 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.

  3. 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).

  4. SUMOylation modulates the transcriptional activity of androgen receptor in a target gene and pathway selective manner.

    Science.gov (United States)

    Sutinen, Päivi; Malinen, Marjo; Heikkinen, Sami; Palvimo, Jorma J

    2014-07-01

    Androgen receptor (AR) plays an important regulatory role in prostate cancer. AR's transcriptional activity is regulated by androgenic ligands, but also by post-translational modifications, such as SUMOylation. To study the role of AR SUMOylation in genuine chromatin environment, we compared androgen-regulated gene expression and AR chromatin occupancy in PC-3 prostate cancer cell lines stably expressing wild-type (wt) or doubly SUMOylation site-mutated AR (AR-K386R,K520R). Our genome-wide gene expression analyses reveal that the SUMOylation modulates the AR function in a target gene and pathway selective manner. The transcripts that are differentially regulated by androgen and SUMOylation are linked to cellular movement, cell death, cellular proliferation, cellular development and cell cycle. Fittingly, SUMOylation mutant AR cells proliferate faster and are more sensitive to apoptosis. Moreover, ChIP-seq analyses show that the SUMOylation can modulate the chromatin occupancy of AR on many loci in a fashion that parallels their differential androgen-regulated expression. De novo motif analyses reveal that FOXA1, C/EBP and AP-1 motifs are differentially enriched at the wtAR- and the AR-K386R,K520R-preferred genomic binding positions. Taken together, our data indicate that SUMOylation does not simply repress the AR activity, but it regulates AR's interaction with the chromatin and the receptor's target gene selection.

  5. 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.

  6. 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.

  7. Selecting Targeted Symptoms/Syndromes for Syndromic Surveillance in Rural China

    Science.gov (United States)

    Tan, Li; Zhang, Jie; Cheng, Liwei; Yan, Weirong; Diwan, Vinod K.; Long, Lu; Nie, Shaofa

    2013-01-01

    Objective To select the potential targeted symptoms/syndromes as early warning indicators for epidemics or outbreaks detection in rural China. Introduction Patients’ chief complaints (CCs) as a common data source, has been widely used in syndromic surveillance due to its timeliness, accuracy and availability (1). For automated syndromic surveillance, CCs always classified into predefined syndromic categories to facilitate subsequent data aggregation and analysis. However, in rural China, most outpatient doctors recorded the information of patients (e.g. CCs) into clinic logs manually rather than computers. Thus, more convenient surveillance method is needed in the syndromic surveillance project (ISSC). And the first and important thing is to select the targeted symptoms/syndromes. Methods Epidemiological analysis was conducted on data from case report system in Jingmen City (one study site in ISSC) from 2004 to 2009. Initial symptoms/syndromes were selected by literature reviews. And finally expert consultation meetings, workshops and field investigation were held to confirm the targeted symptoms/syndromes. Results 10 kinds of infectious diseases, 6 categories of emergencies, and 4 bioterrorism events (i.e. plague, anthrax, botulism and hemorrhagic fever) were chose as specific diseases/events for monitoring (Table 1). Two surveillance schemes were developed by reviewing on 565 literatures about clinical conditions of specific diseases/events and 14 literatures about CCs based syndromic surveillance. The former one was to monitor symptoms (19 initial symptoms), and then aggregation or analysis on single or combined symptom(s); and the other one was to monitor syndromes (9 initial syndromes) directly (Table 2). The consultation meeting and field investigation identified three issues which should be considered: 1) the abilities of doctors especially village doctors to understand the definitions of symptoms/syndromes; 2) the workload of data collection; 3) the

  8. 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.

    2004-12-01

    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.

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

    Science.gov (United States)

    Park, John J.; Buksa, John J.

    1995-09-01

    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.

  10. Semi-automatic measures of activity in selected south polar regions of Mars using morphological image analysis

    Science.gov (United States)

    Aye, Klaus-Michael; Portyankina, Ganna; Pommerol, Antoine; Thomas, Nicolas

    results of these semi-automatically determined seasonal fan count evolutions for Inca City, Ithaca and Manhattan ROIs, compare these evolutionary patterns with each other and with surface reflectance evolutions of both HiRISE and CRISM for the same locations. References: Aye, K.-M. et. al. (2010), LPSC 2010, 2707 Hansen, C. et. al (2010) Icarus, 205, Issue 1, p. 283-295 Kieffer, H.H. (2007), JGR 112 Portyankina, G. et. al. (2010), Icarus, 205, Issue 1, p. 311-320 Thomas, N. et. Al. (2009), Vol. 4, EPSC2009-478

  11. Unusual target selectivity of perisomatic inhibitory cells in the hilar region of the rat hippocampus.

    Science.gov (United States)

    Acsády, L; Katona, I; Martínez-Guijarro, F J; Buzsáki, G; Freund, T F

    2000-09-15

    Perisomatic inhibitory innervation of all neuron types profoundly affects their firing characteristics and vulnerability. In this study we examined the postsynaptic targets of perisomatic inhibitory cells in the hilar region of the dentate gyrus where the proportion of potential target cells (excitatory mossy cells and inhibitory interneurons) is approximately equal. Both cholecystokinin (CCK)- and parvalbumin-immunoreactive basket cells formed multiple contacts on the somata and proximal dendrites of mossy cells. Unexpectedly, however, perisomatic inhibitory terminals arriving from these cell types largely ignored hilar GABAergic cell populations. Eighty-ninety percent of various GABAergic neurons including other CCK-containing basket cells received no input from CCK-positive terminals. Parvalbumin-containing cells sometimes innervated each other but avoided 75% of other GABAergic cells. Overall, a single mossy cell received 40 times more CCK-immunoreactive terminals and 15 times more parvalbumin-positive terminals onto its soma than the cell body of an average hilar GABAergic cell. In contrast to the pronounced target selectivity in the hilar region, CCK- and parvalbumin-positive neurons innervated each other via collaterals in stratum granulosum and moleculare. Our observations indicate that the inhibitory control in the hilar region is qualitatively different from other cortical areas at both the network level and the level of single neurons. The paucity of perisomatic innervation of hilar interneurons should have profound consequences on their action potential generation and on their ensemble behavior. These findings may help explain the unique physiological patterns observed in the hilus and the selective vulnerability of the hilar cell population in various pathophysiological conditions.

  12. Selectivity on-target of bromodomain chemical probes by structure-guided medicinal chemistry and chemical biology.

    Science.gov (United States)

    Galdeano, Carles; Ciulli, Alessio

    2016-09-01

    Targeting epigenetic proteins is a rapidly growing area for medicinal chemistry and drug discovery. Recent years have seen an explosion of interest in developing small molecules binding to bromodomains, the readers of acetyl-lysine modifications. A plethora of co-crystal structures has motivated focused fragment-based design and optimization programs within both industry and academia. These efforts have yielded several compounds entering the clinic, and many more are increasingly being used as chemical probes to interrogate bromodomain biology. High selectivity of chemical probes is necessary to ensure biological activity is due to an on-target effect. Here, we review the state-of-the-art of bromodomain-targeting compounds, focusing on the structural basis for their on-target selectivity or lack thereof. We also highlight chemical biology approaches to enhance on-target selectivity.

  13. 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.

  14. Targeted Curing of All Lysogenic Bacteriophage from Streptococcus pyogenes Using a Novel Counter-selection Technique.

    Directory of Open Access Journals (Sweden)

    Chad W Euler

    Full Text Available Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS, into a targeted prophage on the chromosome of a streptomycin resistant (SmR mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome; the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S

  15. Targeted Curing of All Lysogenic Bacteriophage from Streptococcus pyogenes Using a Novel Counter-selection Technique.

    Science.gov (United States)

    Euler, Chad W; Juncosa, Barbara; Ryan, Patricia A; Deutsch, Douglas R; McShan, W Michael; Fischetti, Vincent A

    2016-01-01

    Streptococcus pyogenes is a human commensal and a bacterial pathogen responsible for a wide variety of human diseases differing in symptoms, severity, and tissue tropism. The completed genome sequences of >37 strains of S. pyogenes, representing diverse disease-causing serotypes, have been published. The greatest genetic variation among these strains is attributed to numerous integrated prophage and prophage-like elements, encoding several virulence factors. A comparison of isogenic strains, differing in prophage content, would reveal the effects of these elements on streptococcal pathogenesis. However, curing strains of prophage is often difficult and sometimes unattainable. We have applied a novel counter-selection approach to identify rare S. pyogenes mutants spontaneously cured of select prophage. To accomplish this, we first inserted a two-gene cassette containing a gene for kanamycin resistance (KanR) and the rpsL wild-type gene, responsible for dominant streptomycin sensitivity (SmS), into a targeted prophage on the chromosome of a streptomycin resistant (SmR) mutant of S. pyogenes strain SF370. We then applied antibiotic counter-selection for the re-establishment of the KanS/SmR phenotype to select for isolates cured of targeted prophage. This methodology allowed for the precise selection of spontaneous phage loss and restoration of the natural phage attB attachment sites for all four prophage-like elements in this S. pyogenes chromosome. Overall, 15 mutants were constructed that encompassed every permutation of phage knockout as well as a mutant strain, named CEM1ΔΦ, completely cured of all bacteriophage elements (a ~10% loss of the genome); the only reported S. pyogenes strain free of prophage-like elements. We compared CEM1ΔΦ to the WT strain by analyzing differences in secreted DNase activity, as well as lytic and lysogenic potential. These mutant strains should allow for the direct examination of bacteriophage relationships within S. pyogenes and

  16. Selective targeting of the conserved active site cysteine of Mycobacterium tuberculosis methionine aminopeptidase with electrophilic reagents.

    Science.gov (United States)

    Reddi, Ravikumar; Arya, Tarun; Kishor, Chandan; Gumpena, Rajesh; Ganji, Roopa J; Bhukya, Supriya; Addlagatta, Anthony

    2014-09-01

    Methionine aminopeptidases (MetAPs) cleave initiator methionine from ~ 70% of the newly synthesized proteins in every living cell, and specific inhibition or knockdown of this function is detrimental. MetAPs are metalloenzymes, and are broadly classified into two subtypes, type I and type II. Bacteria contain only type I MetAPs, and the active site of these enzymes contains a conserved cysteine. By contrast, in type II enzymes the analogous position is occupied by a conserved glycine. Here, we report the reactivity of the active site cysteine in a type I MetAP, MetAP1c, of Mycobacterium tuberculosis (MtMetAP1c) towards highly selective cysteine-specific reagents. The authenticity of selective modification of Cys105 of MtMetAP1c was established by using site-directed mutagenesis and crystal structure determination of covalent and noncovalent complexes. On the basis of these observations, we propose that metal ions in the active site assist in the covalent modification of Cys105 by orienting the reagents appropriately for a successful reaction. These studies establish, for the first time, that the conserved cysteine of type I MetAPs can be targeted for selective inhibition, and we believe that this chemistry can be exploited for further drug discovery efforts regarding microbial MetAPs.

  17. Selective superoxide generation within mitochondria by the targeted redox cycler MitoParaquat.

    Science.gov (United States)

    Robb, Ellen L; Gawel, Justyna M; Aksentijević, Dunja; Cochemé, Helena M; Stewart, Tessa S; Shchepinova, Maria M; Qiang, He; Prime, Tracy A; Bright, Thomas P; James, Andrew M; Shattock, Michael J; Senn, Hans M; Hartley, Richard C; Murphy, Michael P

    2015-12-01

    Superoxide is the proximal reactive oxygen species (ROS) produced by the mitochondrial respiratory chain and plays a major role in pathological oxidative stress and redox signaling. While there are tools to detect or decrease mitochondrial superoxide, none can rapidly and specifically increase superoxide production within the mitochondrial matrix. This lack impedes progress, making it challenging to assess accurately the roles of mitochondrial superoxide in cells and in vivo. To address this unmet need, we synthesized and characterized a mitochondria-targeted redox cycler, MitoParaquat (MitoPQ) that comprises a triphenylphosphonium lipophilic cation conjugated to the redox cycler paraquat. MitoPQ accumulates selectively in the mitochondrial matrix driven by the membrane potential. Within the matrix, MitoPQ produces superoxide by redox cycling at the flavin site of complex I, selectively increasing superoxide production within mitochondria. MitoPQ increased mitochondrial superoxide in isolated mitochondria and cells in culture ~a thousand-fold more effectively than untargeted paraquat. MitoPQ was also more toxic than paraquat in the isolated perfused heart and in Drosophila in vivo. MitoPQ enables the selective generation of superoxide within mitochondria and is a useful tool to investigate the many roles of mitochondrial superoxide in pathology and redox signaling in cells and in vivo.

  18. CarPrice versus CarpRice: Word Boundary Ambiguity Influences Saccade Target Selection during the Reading of Chinese Sentences

    Science.gov (United States)

    Yan, Ming; Kliegl, Reinhold

    2016-01-01

    As a contribution to a theoretical debate about the degree of high-level influences on saccade targeting during sentence reading, we investigated eye movements during the reading of structurally ambiguous Chinese character strings and examined whether parafoveal word segmentation could influence saccade-target selection. As expected, ambiguous…

  19. Automatic Selection Algorithm of Mandarin Corpus for Voice Conversion%面向语音转换的汉语语料自动选取算法

    Institute of Scientific and Technical Information of China (English)

    沈亚敏; 赵晖; 张权; 唐朝京

    2011-01-01

    In order to realize voice conversion, a satisfied voice conversion corpus needs to be built up.This paper proposes an automatic corpus selection algorithm based on the semi-syllable model.Because the number of corpus sentences is small for voice conversion, the semi-syllable is chosen as the basic unit of the corpus.The algorithm automatically selects corpus from original corpus.An evaluation function is utilized to score sentences from original corpus according to the number and the kind of semi-syllable.When the number of chosen sentences is 615, the set of selected text covers 97.8% of the semi-syllables.The covering rate, coverage efficiency and sparse rate are obviously better than that of conventional algorithms.%为实现语音转换,建立符合要求的汉语语音转换语料库,提出一种基于半音节模型的语料自动选取算法.根据语音转换训练时需要语料数量较少的特征,选择半音节作为语料库的基本单位.在此基础上,从原始语料中自动选取语料,根据语音转换对说话人特征较敏感的情况,利用评估函数并根据半音节的出现次数对原始语料中的句子进行打分.实验结果表明,与传统算法相比,该算法在语音库自动选取615句汉语语料时,可以覆盖97.8%的带声调半音节,其覆盖效率、覆盖率和稀疏度有较大改进.

  20. 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

  1. Cold atmospheric plasma treatment selectively targets head and neck squamous cell carcinoma cells.

    Science.gov (United States)

    Guerrero-Preston, Rafael; Ogawa, Takenori; Uemura, Mamoru; Shumulinsky, Gary; Valle, Blanca L; Pirini, Francesca; Ravi, Rajani; Sidransky, David; Keidar, Michael; Trink, Barry

    2014-10-01

    The treatment of locoregional recurrence (LRR) of head and neck squamous cell carcinoma (HNSCC) often requires a combination of surgery, radiation therapy and/or chemotherapy. Survival outcomes are poor and the treatment outcomes are morbid. Cold atmospheric plasma (CAP) is an ionized gas produced at room temperature under laboratory conditions. We have previously demonstrated that treatment with a CAP jet device selectively targets cancer cells using in vitro melanoma and in vivo bladder cancer models. In the present study, we wished to examine CAP selectivity in HNSCC in vitro models, and to explore its potential for use as a minimally invasive surgical approach that allows for specific cancer cell or tumor tissue ablation without affecting the surrounding healthy cells and tissues. Four HNSCC cell lines (JHU-022, JHU-028, JHU-029, SCC25) and 2 normal oral cavity epithelial cell lines (OKF6 and NOKsi) were subjected to cold plasma treatment for durations of 10, 30 and 45 sec, and a helium flow of 20 l/min-1 for 10 sec was used as a positive treatment control. We showed that cold plasma selectively diminished HNSCC cell viability in a dose-response manner, as evidenced by MTT assays; the viability of the OKF6 cells was not affected by the cold plasma. The results of colony formation assays also revealed a cell-specific response to cold plasma application. Western blot analysis did not provide evidence that the cleavage of PARP occurred following cold plasma treatment. In conclusion, our results suggest that cold plasma application selectively impairs HNSCC cell lines through non-apoptotic mechanisms, while having a minimal effect on normal oral cavity epithelial cell lines.

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

    Science.gov (United States)

    Narahashi, T; Zhao, X; Ikeda, T; Nagata, K; Yeh, J Z

    2007-04-01

    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. Pyrethroids keep the sodium channels open for a prolonged period of time, causing elevation of the depolarizing after-potential. Once the after-potential reaches the threshold for excitation, repetitive after-discharges are produced, resulting in hyperexcitation of intoxicated animals. Only about 1% of sodium channels needs to be modified to produce hyperexcitation, indicating a high degree of toxicity amplification from sodium channels to animals. Pyrethroids were >1000-fold more potent on cockroach sodium channels than rat sodium channels, and this forms the most significant factor to explain the selective toxicity of pyrethroids in insects over mammals. Fipronil, a phenylpyrazole, is known to act on the gamma-aminobutyric acid receptor to block the chloride channel. It is effective against certain species of insects that have become resistant to most insecticides, including those acting on the gamma-aminobutyric acid receptor, and is much more toxic to insects than to mammals. Recently, fipronil has been found to block glutamate-activated chloride channels in cockroach neurons in a potent manner. Since mammals are devoid of this type of chloride channel, fipronil block of the glutamate-activated chloride channel is deemed responsible, at least partially, for the higher selective toxicity to insects over mammals and for the lack of cross-resistance.

  3. Deontic reasoning as a target of selection: reply to Astington and Dack.

    Science.gov (United States)

    Cummins, Denise Dellarosa

    2013-12-01

    In their discussion of young children's deontic reasoning performance, Astington and Dack (2013) made the following claims: (1) Children need more cues to elicit cogent social norm reasoning than adults require, namely, explicit reference to authority; (2) Deontic reasoning improves with age, and this is evidence against a nativist view; (3) All evolutionary explanations of deontic reasoning advantages require positing a ''domain-specific deontic reasoning module."; and (4) young children excel at deontic reasoning because it is easier. Here, I refute each claim. Instead, I argue that (1) Social norm reasoning is one type of deontic reasoning that has been the target of selective pressure; (2) Development does not preclude nativism; (3) Epistemic utterances make no greater processing demands than deontic utterances; and (4) both adult and child norm reasoning performance is strongly influenced by reference to or implication of authority.

  4. Gene Therapy for Advanced Melanoma: Selective Targeting and Therapeutic Nucleic Acids

    Directory of Open Access Journals (Sweden)

    Joana R. Viola

    2013-01-01

    Full Text Available Despite recent advances, the treatment of malignant melanoma still results in the relapse of the disease, and second line treatment mostly fails due to the occurrence of resistance. A wide range of mutations are known to prevent effective treatment with chemotherapeutic drugs. Hence, approaches with biopharmaceuticals including proteins, like antibodies or cytokines, are applied. As an alternative, regimens with therapeutically active nucleic acids offer the possibility for highly selective cancer treatment whilst avoiding unwanted and toxic side effects. This paper gives a brief introduction into the mechanism of this devastating disease, discusses the shortcoming of current therapy approaches, and pinpoints anchor points which could be harnessed for therapeutic intervention with nucleic acids. We bring the delivery of nucleic acid nanopharmaceutics into perspective as a novel antimelanoma therapeutic approach and discuss the possibilities for melanoma specific targeting. The latest reports on preclinical and already clinical application of nucleic acids in melanoma are discussed.

  5. Structural determinants of host defense peptides for antimicrobial activity and target cell selectivity.

    Science.gov (United States)

    Takahashi, Daisuke; Shukla, Sanjeev K; Prakash, Om; Zhang, Guolong

    2010-09-01

    Antimicrobial host defense peptides (HDPs) are a critical component of the innate immunity with microbicidal, endotoxin-neutralizing, and immunostimulatory properties. HDPs kill bacteria primarily through non-specific membrane lysis, therefore with a less likelihood of provoking resistance. Extensive structure-activity relationship studies with a number of HDPs have revealed that net charge, amphipathicity, hydrophobicity, and structural propensity are among the most important physicochemical and structural parameters that dictate their ability to interact with and disrupt membranes. A delicate balance among these factors, rather than a mere alteration of a single factor, is critically important for HDPs to ensure the antimicrobial potency and target cell selectivity. With a better understanding of the structural determinants of HDPs for their membrane-lytic activities, it is expected that novel HDP-based antimicrobials with minimum toxicity to eukaryotic cells can be developed for resistant infections, which have become a global public health crisis.

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

    Science.gov (United States)

    Nikolaev, Andrey R.; Jurica, Peter; Nakatani, Chie; Plomp, Gijs; van Leeuwen, Cees

    2013-01-01

    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. PMID:23818877

  7. 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.

  8. Targeting LSCs through membrane antigens selectively or preferentially expressed on these cells.

    Science.gov (United States)

    Pelosi, Elvira; Castelli, Germana; Testa, Ugo

    2015-12-01

    Studies of xenotransplantation of bone marrow and blood cells of AML patients have supported the existence of rare leukemic stem cells, able to initiate and maintain the leukemic process and bearing the typical leukemic abnormalities. LSCs possess self-renewal capacity and are responsible for the growth of the more differentiated leukemic progeny in the bone marrow and in the blood. These cells are more resistant than bulk leukemic cells to anti-leukemic drugs, thus survive to treatment and are, at a large extent, responsible for leukemia relapse. During the last two decades, considerable progresses have been made in the understanding of the peculiar cellular and molecular properties of LSCs. In this context, particularly relevant was the discovery of several membrane markers, selectively or preferentially expressed on LSCs. These membrane markers offer now unique opportunities to identify LSCs and to distinguish them from normal HSCs, to monitor the response of the various anti-leukemic treatments at the level of the LSC compartment, to identify relevant therapeutic targets. Concerning this last point, the most promising therapeutic targets are CD33 and CD123.

  9. Searching for life on Mars: selection of molecular targets for ESA's aurora ExoMars mission.

    Science.gov (United States)

    Parnell, John; Cullen, David; Sims, Mark R; Bowden, Stephen; Cockell, Charles S; Court, Richard; Ehrenfreund, Pascale; Gaubert, Francois; Grant, William; Parro, Victor; Rohmer, Michel; Sephton, Mark; Stan-Lotter, Helga; Steele, Andrew; Toporski, Jan; Vago, Jorge

    2007-08-01

    The European Space Agency's ExoMars mission will seek evidence of organic compounds of biological and non-biological origin at the martian surface. One of the instruments in the Pasteur payload may be a Life Marker Chip that utilizes an immunoassay approach to detect specific organic molecules or classes of molecules. Therefore, it is necessary to define and prioritize specific molecular targets for antibody development. Target compounds have been selected to represent meteoritic input, fossil organic matter, extant (living, recently dead) organic matter, and contamination. Once organic molecules are detected on Mars, further information is likely to derive from the detailed distribution of compounds rather than from single molecular identification. This will include concentration gradients beneath the surface and gradients from generic to specific compounds. The choice of biomarkers is informed by terrestrial biology but is wide ranging, and nonterrestrial biology may be evident from unexpected molecular distributions. One of the most important requirements is to sample where irradiation and oxidation are minimized, either by drilling or by using naturally excavated exposures. Analyzing regolith samples will allow for the search of both extant and fossil biomarkers, but sequential extraction would be required to optimize the analysis of each of these in turn.

  10. 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.

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

    Science.gov (United States)

    Frenzel, Anna; Zirath, Hanna; Vita, Marina; Albihn, Ami; Henriksson, Marie Arsenian

    2011-01-01

    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.

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

    Science.gov (United States)

    Kumar, Rajeev; Verma, Vikas; Sharma, Vikas; Jain, Ashish; Singh, Vishal; Sarswat, Amit; Maikhuri, Jagdamba P; Sharma, Vishnu L; Gupta, Gopal

    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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Qi, Weiwei; Du, Xiangke [Peking University People' s Hospital, Beijing (China); Li, Jianying [GE Healthcare China, Beijing (China)

    2009-12-15

    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.

  14. An Algorithm to Identify Target-Selective Ligands – A Case Study of 5-HT7/5-HT1A Receptor Selectivity

    Science.gov (United States)

    Kurczab, Rafał; Canale, Vittorio; Zajdel, Paweł; Bojarski, Andrzej J.

    2016-01-01

    A computational procedure to search for selective ligands for structurally related protein targets was developed and verified for serotonergic 5-HT7/5-HT1A receptor ligands. Starting from a set of compounds with annotated activity at both targets (grouped into four classes according to their activity: selective toward each target, not-selective and not-selective but active) and with an additional set of decoys (prepared using DUD methodology), the SVM (Support Vector Machines) models were constructed using a selective subset as positive examples and four remaining classes as negative training examples. Based on these four component models, the consensus classifier was then constructed using a data fusion approach. The combination of two approaches of data representation (molecular fingerprints vs. structural interaction fingerprints), different training set sizes and selection of the best SVM component models for consensus model generation, were evaluated to determine the optimal settings for the developed algorithm. The results showed that consensus models with molecular fingerprints, a larger training set and the selection of component models based on MCC maximization provided the best predictive performance. PMID:27271158

  15. An Algorithm to Identify Target-Selective Ligands - A Case Study of 5-HT7/5-HT1A Receptor Selectivity.

    Directory of Open Access Journals (Sweden)

    Rafał Kurczab

    Full Text Available A computational procedure to search for selective ligands for structurally related protein targets was developed and verified for serotonergic 5-HT7/5-HT1A receptor ligands. Starting from a set of compounds with annotated activity at both targets (grouped into four classes according to their activity: selective toward each target, not-selective and not-selective but active and with an additional set of decoys (prepared using DUD methodology, the SVM (Support Vector Machines models were constructed using a selective subset as positive examples and four remaining classes as negative training examples. Based on these four component models, the consensus classifier was then constructed using a data fusion approach. The combination of two approaches of data representation (molecular fingerprints vs. structural interaction fingerprints, different training set sizes and selection of the best SVM component models for consensus model generation, were evaluated to determine the optimal settings for the developed algorithm. The results showed that consensus models with molecular fingerprints, a larger training set and the selection of component models based on MCC maximization provided the best predictive performance.

  16. 基于DIVA模型的语音-映射单元自动获取%Automatic acquisition of speech sound-target cells based on DIVA model

    Institute of Scientific and Technical Information of China (English)

    张少白; 刘欣

    2013-01-01

    针对DIVA模型中存在的“感知能力与语音生成技巧发育不平衡”问题,提出了一种自动获取语音-映射单元的方法。该方法将人耳模拟为一个具有不同带宽的并联带通滤波器组,分别与模型中21维度的听觉存储空间相关联,对不同听觉的不同反应,分别考虑其频带的屏蔽效应、听觉响度与频率的关系。在读取语音输入信号的过程中,模型能较好地获得初始听觉表示,其方式与婴儿咿呀学语的过程基本一致。仿真实验表明,通过边界定义、相似性比较以及搜索更新等步骤,此方法能很好地进行初始输入模式的自组织匹配,并最终使DIVA模型更具语音获取的自然特性。%Contraposing the shortage of Directions Into Velocities of Articulators ( DIVA) model about“infants per-ceptual abilities do develop faster at first than their speech production skills”, the paper presents an automatic ac-quisition method of speech sound-target cells. The method simulates the human ear as a parallel band-pass filter group with different bandwidth and associates respectively;the filter with the 21-dimensional storage space of audi-tory sense in DIVA model. This method was done in order for different auditory reactions, the shielding effect of fre-quency band, sound loudness, and frequency relation could be considered respectively for this study. In the process of reading the input signal of speech, the model can acquire good initial hearing and the process is consistent with baby's babble. The simulation results show that through boundary definition, similarity comparison, searching and updates and so on, the method has nicer self-organized pattern matching effect for initial input, which makes the DIVA model a more natural characteristic regarding speech acquisition.

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

    Science.gov (United States)

    Wang, Yu; Li, Wei; Xia, Yingying; Wang, Chongzhi; Tang, Y Tom; Guo, Wenying; Li, Jinliang; Zhao, Xia; Sun, Yepeng; Hu, Juan; Zhen, Hefu; Zhang, Xiandong; Chen, Chao; Shi, Yujian; Li, Lin; Cao, Hongzhi; Du, Hongli; Li, Jian

    2014-01-01

    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.

  18. 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.

  19. 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.

  20. 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.

  1. Fast and behavior-selective exploitation of a marine fish targeted by anglers

    Science.gov (United States)

    Alós, Josep; Palmer, Miquel; Rosselló, Rosario; Arlinghaus, Robert

    2016-12-01

    Harvesting of wild-living animals is often intensive and may selectively target heritable behavioral traits. We studied the exploitation dynamics and the vulnerability consequences of individual heterogeneity in movement-related behaviors in free-ranging pearly razorfish (Xyrichthys novacula). Using underwater-video recording, we firstly document a fast and high exploitation rate of about 60% of the adult population removed in just few days after the opening of the season. Subsequently, we tagged a sample of individuals with acoustic transmitters and studied whether behavioral traits were significant predictors of the vulnerability to angling. Tagged individuals revealed repeatable behaviors in several home range-related traits, suggesting the presence of spatial behavioral types. The individuals surviving the experimental fishery showed only localized and low-intensity movement patterns. Our study provides new insights for understanding the harvesting pressures and selective properties acting on behavioral traits of recreational fishing. Many fish stocks around the globe are today predominantly exploited by recreational fisheries. The fisheries-induced change in fish behavior described here may be therefore widespread, and has the potential to alter food-webs, profitability of the fisheries and to affect stock assessment by eroding catchability in the long-term.

  2. 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.)

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

    Science.gov (United States)

    She, Ji; Wang, Fei; Zhou, Jianjiang

    2016-12-21

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

  4. Control of working memory: effects of attention training on target recognition and distractor salience in an auditory selection task.

    Science.gov (United States)

    Melara, Robert D; Tong, Yunxia; Rao, Aparna

    2012-01-09

    Behavioral and electrophysiological measures of target and distractor processing were examined in an auditory selective attention task before and after three weeks of distractor suppression training. Behaviorally, training improved target recognition and led to less conservative and more rapid responding. Training also effectively shortened the temporal distance between distractors and targets needed to achieve a fixed level of target sensitivity. The effects of training on event-related potentials were restricted to the distracting stimulus: earlier N1 latency, enhanced P2 amplitude, and weakened P3 amplitude. Nevertheless, as distractor P2 amplitude increased, so too did target P3 amplitude, connecting experience-dependent changes in distractor processing with greater distinctiveness of targets in working memory. We consider the effects of attention training on the processing priorities, representational noise, and inhibitory processes operating in working memory.

  5. Automatic Control System for Neutron Laboratory Safety

    Institute of Scientific and Technical Information of China (English)

    ZHAO; Xiao; ZHANG; Guo-guang; FENG; Shu-qiang; SU; Dan; YANG; Guo-zhao; ZHANG; Shuai

    2015-01-01

    In order to cooperate with the experiment of neutron generator,and realize the automatic control in the experiment,a set of automatic control system for the safety of the neutron laboratory is designed.The system block diagram is shown as Fig.1.Automatic control device is for processing switch signal,so PLC is selected as the core component

  6. Cancer cell-selective promoter recognition accompanies antitumor effect by glucocorticoid receptor-targeted gold nanoparticle

    Science.gov (United States)

    Sau, Samaresh; Agarwalla, Pritha; Mukherjee, Sudip; Bag, Indira; Sreedhar, Bojja; Pal-Bhadra, Manika; Patra, Chitta Ranjan; Banerjee, Rajkumar

    2014-05-01

    Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied on the delivery of `exogenous' genes invoking gene knockdown or replacement. Practically, there are no instances for the nanoparticle-mediated promoter regulation of `endogenous' genes, more so, as a cancer selective phenomenon. In this regard, we report the development of a simple, easily modifiable GNP-formulation, which promoted/up-regulated the expression of a specific category of `endogenous' genes, the glucocorticoid responsive genes. This genetic up-regulation was induced in only cancer cells by modified GNP-mediated transcriptional activation of its cytoplasmic receptor, glucocorticoid receptor (GR). Normal cells and their GR remained primarily unperturbed by this GNP-formulation. The most potent gene up-regulating GNP-formulation down-regulated a cancer-specific proliferative signal, phospho-Akt in cancer cells, which accompanied retardation of tumor growth in the murine melanoma model. We show that GR-targeted GNPs may find potential use in the targeting and modulation of genetic information in cancer towards developing novel anticancer therapeutics.Nanoparticles, such as gold nanoparticles (GNP), upon convenient modifications perform multi tasks catering to many biomedical applications. However, GNP or any other type of nanoparticles is yet to achieve the feat of intracellular regulation of endogenous genes of choice such as through manipulation of a gene-promoter in a chromosome. As for gene modulation and delivery, GNP (or other nanoparticles) showed only limited gene therapy potential, which relied

  7. Target selected treatment with levamisole to control the development of anthelmintic resistance in a sheep flock.

    Science.gov (United States)

    Chagas, Ana Carolina de Souza; Domingues, Luciana Ferreira; Gaínza, Yousmel Alemán; Barioni-Júnior, Waldomiro; Esteves, Sérgio Novita; Niciura, Simone Cristina Méo

    2016-03-01

    Levamisole phosphate, chosen based on its 100 % efficacy demonstrated by a previous fecal egg count reduction test (FECRT), was used as the exclusive anthelmintic treatment in the Embrapa Southeast Livestock sheep flock from 2009 to 2014 in a target selected treatment scheme. In the present study, the effectiveness of this nematode control scheme was evaluated after 5 years by FECRT, larval development test (LDT), and a molecular test to assess the development of levamisole resistance in Haemonchus contortus. Animals were submitted to treatments with albendazole, levamisole, closantel, ivermectin, moxidectin, and monepantel. Eggs per gram of feces (EPG) counts and fecal cultures were performed, and anthelmintic efficacy was calculated by the RESO 4.0 program. The helminths of the flock (GIN Embrapa2014) were compared to susceptible (McMaster) and resistant (Embrapa2010) H. contortus isolates in the LDT to estimate the LC50 and LC90 of levamisole and in a molecular test to evaluate the 63-bp indel in the acr8 gene associated with levamisole resistance. In the FECRT, parasites were susceptible to monepantel (99.6 %) and closantel (98.3 %), but resistant to moxidectin (93.8 %), levamisole (70.4 %), ivermectin (48.1 %), and albendazole (0 %). In the coproculture on D14, and the control group presented 80 % H. contortus and 20 % Trichostrongylus sp., while in the monepantel group L1 were observed as well as Oesophagostomum sp. L3. LDT and resistance factors provided good separation between susceptible and resistant parasites. The genotypic frequencies of the 63-bp insertion in the acr8 gene in H. contortus were 11.9, 6.7, and 0 % in GIN Embrapa2014, Embrapa2010, and McMaster isolates, respectively. After 5 years of exclusive use, the nematodes developed resistance to levamisole, detected by FECRT and by increase in LC50 and LC90 for levamisole in the LDT. The 63-bp indel was not confirmed as a molecular marker of levamisole resistance in our isolates. The target

  8. Interval MULTIMOORA method with target values of attributes based on interval distance and preference degree: biomaterials selection

    Science.gov (United States)

    Hafezalkotob, Arian; Hafezalkotob, Ashkan

    2016-12-01

    A target-based MADM method covers beneficial and non-beneficial attributes besides target values for some attributes. Such techniques are considered as the comprehensive forms of MADM approaches. Target-based MADM methods can also be used in traditional decision-making problems in which beneficial and non-beneficial attributes only exist. In many practical selection problems, some attributes have given target values. The values of decision matrix and target-based attributes can be provided as intervals in some of such problems. Some target-based decision-making methods have recently been developed; however, a research gap exists in the area of MADM techniques with target-based attributes under uncertainty of information. We extend the MULTIMOORA method for solving practical material selection problems in which material properties and their target values are given as interval numbers. We employ various concepts of interval computations to reduce degeneration of uncertain data. In this regard, we use interval arithmetic and introduce innovative formula for interval distance of interval numbers to create interval target-based normalization technique. Furthermore, we use a pairwise preference matrix based on the concept of degree of preference of interval numbers to calculate the maximum, minimum, and ranking of these numbers. Two decision-making problems regarding biomaterials selection of hip and knee prostheses are discussed. Preference degree-based ranking lists for subordinate parts of the extended MULTIMOORA method are generated by calculating the relative degrees of preference for the arranged assessment values of the biomaterials. The resultant rankings for the problem are compared with the outcomes of other target-based models in the literature.

  9. Selection and affinity maturation of IgNAR variable domains targeting Plasmodium falciparum AMA1.

    Science.gov (United States)

    Nuttall, Stewart D; Humberstone, Karen S; Krishnan, Usha V; Carmichael, Jennifer A; Doughty, Larissa; Hattarki, Meghan; Coley, Andrew M; Casey, Joanne L; Anders, Robin F; Foley, Michael; Irving, Robert A; Hudson, Peter J

    2004-04-01

    The new antigen receptor (IgNAR) is an antibody unique to sharks and consists of a disulphide-bonded dimer of two protein chains, each containing a single variable and five constant domains. The individual variable (V(NAR)) domains bind antigen independently, and are candidates for the smallest antibody-based immune recognition units. We have previously produced a library of V(NAR) domains with extensive variability in the CDR1 and CDR3 loops displayed on the surface of bacteriophage. Now, to test the efficacy of this library, and further explore the dynamics of V(NAR) antigen binding we have performed selection experiments against an infectious disease target, the malarial Apical Membrane Antigen-1 (AMA1) from Plasmodium falciparum. Two related V(NAR) clones were selected, characterized by long (16- and 18-residue) CDR3 loops. These recombinant V(NAR)s could be harvested at yields approaching 5mg/L of monomeric protein from the E. coli periplasm, and bound AMA1 with nanomolar affinities (K(D)= approximately 2 x 10(-7) M). One clone, designated 12Y-2, was affinity-matured by error prone PCR, resulting in several variants with mutations mapping to the CDR1 and CDR3 loops. The best of these variants showed approximately 10-fold enhanced affinity over 12Y-2 and was Plasmodium falciparum strain-specific. Importantly, we demonstrated that this monovalent V(NAR) co-localized with rabbit anti-AMA1 antisera on the surface of malarial parasites and thus may have utility in diagnostic applications.

  10. ATP-Competitive Inhibitors of the Mammalian Target of Rapamycin: Design and Synthesis of Highly Potent and Selective Pyrazolopyrimidines

    Energy Technology Data Exchange (ETDEWEB)

    Zask, Arie; Verheijen, Jeroen C.; Curran, Kevin; Kaplan, Joshua; Richard, David J.; Nowak, Pawel; Malwitz, David J.; Brooijmans, Natasja; Bard, Joel; Svenson, Kristine; Lucas, Judy; Toral-Barza, Lourdes; Zhang, Wei-Guo; Hollander, Irwin; Gibbons, James J.; Abraham, Robert T.; Ayral-Kaloustian, Semiramis; Mansour, Tarek S.; Yu, Ker; (Wyeth)

    2009-09-18

    The mammalian target of rapamycin (mTOR), a central regulator of growth, survival, and metabolism, is a validated target for cancer therapy. Rapamycin and its analogues, allosteric inhibitors of mTOR, only partially inhibit one mTOR protein complex. ATP-competitive, global inhibitors of mTOR that have the potential for enhanced anticancer efficacy are described. Structural features leading to potency and selectivity were identified and refined leading to compounds with in vivo efficacy in tumor xenograft models.

  11. Selective Targeting of G-Quadruplex Structures by a Benzothiazole-Based Binding Motif.

    Science.gov (United States)

    Buchholz, Ina; Karg, Beatrice; Dickerhoff, Jonathan; Sievers-Engler, Adrian; Lämmerhofer, Michael; Weisz, Klaus

    2017-03-09

    A benzothiazole derivative was identified as potent ligand for DNA G-quadruplex structures. Fluorescence titrations revealed selective binding to quadruplexes of different topologies including parallel, antiparallel and (3+1) hybrid structures. The parallel c-MYC sequence was found to constitute the preferred target with dissociation constants in the micromolar range. Binding of the benzothiazole-based ligand to c-MYC was structurally and thermodynamically characterized in detail by employing a comprehensive set of spectroscopic and calorimetric techniques. Job plot analyses and mass spectral data indicate non-cooperative ligand binding to form 1:1 and 2:1 complex stoichiometries. Whereas stacking interactions are suggested by optical methods, NMR chemical shift perturbations also indicate significant rearrangements of both 5'- and 3'-flanking sequences upon ligand binding. Additional isothermal calorimetry studies yield a thermodynamic profile of the ligand-quadruplex association and reveal enthalpic contributions to be the major driving force for binding. The structural and thermodynamic information obtained in the present work provides the basis for the rational development of benzothiazole derivatives as promising quadruplex binding agents.

  12. 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.

  13. An Assessment of the Effect of Rotenone on Selected Non-Target Aquatic Fauna.

    Science.gov (United States)

    Dalu, Tatenda; Wasserman, Ryan J; Jordaan, Martine; Froneman, William P; Weyl, Olaf L F

    2015-01-01

    Rotenone, a naturally occurring ketone, is widely employed for the management of invasive fish species. The use of rotenone poses serious challenges to conservation practitioners due to its impacts on non-target organisms including amphibians and macroinvertebrates. Using laboratory studies, we investigated the effects of different rotenone concentrations (0, 12.5, 25, 37.5, 50, 100 μg L-1) on selected invertebrate groups; Aeshnidae, Belostomatids, Decapods, Ephemeroptera, Pulmonata and zooplankton over a period of 18 hours. Based on field observations and body size, we hypothesized that Ephemeropterans and zooplankton would be more susceptible to rotenone than Decapods, Belostomatids and snails. Experimental results supported this hypothesis and mortality and behaviour effects varied considerably between taxa, ranging from no effect (crab Potamonuates sidneyi) to 100% mortality (Daphnia pulex and Paradiaptomus lamellatus). Planktonic invertebrates were particularly sensitive to rotenone even at very low concentrations. Future research should investigate the recovery time of invertebrate communities after the application of rotenone and conduct field assessments assessing the longer term effects of rotenone exposure on the population dynamics of those less sensitive organisms.

  14. 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.

  15. Tumour-selective targeting of drug metabolizing enzymes to treat metastatic cancer.

    Science.gov (United States)

    Wierdl, Monika; Tsurkan, Lyudmila; Hatfield, M Jason; Potter, Philip M

    2016-10-01

    Carboxylesterases (CEs) are ubiquitous enzymes responsible for the detoxification of ester-containing xenobiotics. This hydrolysis reaction results in the formation of the corresponding carboxylic acid and alcohol. Due to their highly plastic active site, CEs can hydrolyze structurally very distinct and complex molecules. Because ester groups significantly increase the water solubility of compounds, they are frequently used in the pharmaceutical industry to make relatively insoluble compounds more bioavailable. By default, this results in CEs playing a major role in the distribution and metabolism of these esterified drugs. However, this can be exploited to selectively improve compound hydrolysis, and using specific in vivo targeting techniques can be employed to generate enhanced drug activity. Here, we seek to detail the human CEs involved in esterified molecule hydrolysis, compare and contrast these with CEs present in small mammals and describe novel methods to improve drug therapy by specific delivery of CEs to cells in vivo. Finally, we will discuss the development of such approaches for their potential application towards malignant disease.

  16. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Cross, Sarah E; Gimzewski, James K [Department of Chemistry and Biochemistry, University of California, Los Angeles, CA 90095 (United States); Jin Yusheng [Department of Pathology and Laboratory Medicine, University of California, Los Angeles, CA 90095 (United States); Lu Qingyi [Department of Medicine, Center for Human Nutrition, University of California, Los Angeles, CA 90095 (United States); Rao Jianyu, E-mail: JRao@mednet.ucla.edu, E-mail: gim@chem.ucla.edu [California NanoSystems Institute, University of California, Los Angeles, CA 90095 (United States)

    2011-05-27

    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.

  18. 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.

  19. Chemical biology based on target-selective degradation of proteins and carbohydrates using light-activatable organic molecules.

    Science.gov (United States)

    Toshima, Kazunobu

    2013-05-01

    Proteins and carbohydrates play crucial roles in a wide range of biological processes, including serious diseases. The development of novel and innovative methods for selective control of specific proteins and carbohydrates functions has attracted much attention in the field of chemical biology. In this account article, the development of novel chemical tools, which can degrade target proteins and carbohydrates by irradiation with a specific wavelength of light under mild conditions without any additives, is introduced. This novel class of photochemical agents promise bright prospects for finding not only molecular-targeted bioprobes for understanding of the structure-activity relationships of proteins and carbohydrates but also novel therapeutic drugs targeting proteins and carbohydrates.

  20. 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 ...

  1. Deciding Where to Attend: Priming of Pop-Out Drives Target Selection

    Science.gov (United States)

    Brascamp, Jan W.; Blake, Randolph; Kristjansson, Arni

    2011-01-01

    With attention and eye-movements humans orient to targets of interest. This orienting occurs faster when the same target repeats: priming of pop-out (PoP). While reaction times (RTs) can be important, PoP's real function could be to steer "where" to orient, a possibility underexposed in many current paradigms, as these predesignate a target to…

  2. Targeting of captopril to the kidney : towards selective renal ACE inhibition

    NARCIS (Netherlands)

    Kok, Robbert Jan

    1998-01-01

    The present thesis deals with the targeting of the angiotensin converting enzyme (ACE) inhibiting drug captopril to the kidney. Drug targeting is a technique that aims at a more specific action of drugs by restricting their distribution to a specific part of the body. In other words, the targeting o

  3. Microbial metabolomics: Replacing trial-and-error by the unbiased selection and ranking of targets

    NARCIS (Netherlands)

    Werf, M.J. van der; Jellema, R.H.; Hankemeier, T.

    2005-01-01

    Microbial production strains are currently improved using a combination of random and targeted approaches. In the case of a targeted approach, potential bottlenecks, feed-back inhibition, and side-routes are removed, and other processes of interest are targeted by overexpressing or knocking-out the

  4. Automatic Reading

    Institute of Scientific and Technical Information of China (English)

    胡迪

    2007-01-01

    <正>Reading is the key to school success and,like any skill,it takes practice.A child learns to walk by practising until he no longer has to think about how to put one foot in front of the other.The great athlete practises until he can play quickly,accurately and without thinking.Ed- ucators call it automaticity.

  5. Simulation of emission molecular spectra by a semi-automatic programme package: the case of C2 and CN diatomic molecules emitting during laser ablation of a graphite target in nitrogen environment.

    Science.gov (United States)

    Acquaviva, S

    2004-07-01

    Some emission spectra of diatomic molecules were calculated by a semi-automatic programme package in order to infer the rotational and vibrational temperatures in Boltzmann distribution by comparing them with the corresponding experimental ones. The calculation procedure was applied in the case of CN radical and C2 molecule whose optical emission spectra were recorded during pulsed excimer laser ablation of a graphite target in low-pressure nitrogen environment. Computed similar or dissimilar values of rotational and vibrational temperatures let to verify the existence or not of local thermodynamic equilibrium and to hypothesise the temporal range necessary to establish it in such experiments.

  6. 基于FIS和RBFN的预想事故自动选择%Automatic Contingency Selection Based on Fuzzy Inference System and Radial Basis Function Network

    Institute of Scientific and Technical Information of China (English)

    陈刚; 田志平

    2011-01-01

    针对电力系统预想事故自动选择问题,提出了一种基于模糊推理系统FIS(fuzzy inference system)和径向基函数网络RBFN(radial basis function network)算法.定义了一种有功行为指标PIpf,该指标添加了一个模糊补偿系数用以改善遮蔽现象;同时构造了一个三层的RBFN,该网络以发电机功率、负荷功率和网络拓扑结构作为输入,以PIpf作为输出,并通过离线潮流计算获得训练样本;对算例进行计算并与其他算法比较,结果显示该算法能使事故排序更为合理,且计算精度和速度都令人满意.%In view of the problems of automatic contingency selection of power system, an advanced algorithm is proposed, which is based on fuzzy inference system(FIS) and radial basis function network(RBFN). Firstly an active performance index is defined, which adds a fuzzy compensation factor coefficient to improve shelter phenomenon. Meanwhile a three-layer RBFN is constructed, which treats generator power, load power and network topology as inputs, while treats the active performance index as output. The results of off-line load flow calculation are used to train the RBFN. Finally, the proposed method is demonstrated by an example, compared with several other algorithms. And the results show that the ranking of contingency is much more reasonable, and the calculation accuracy and speed are satisfied.

  7. Using suggestion to model different types of automatic writing.

    Science.gov (United States)

    Walsh, E; Mehta, M A; Oakley, D A; Guilmette, D N; Gabay, A; Halligan, P W; Deeley, Q

    2014-05-01

    Our sense of self includes awareness of our thoughts and movements, and our control over them. This feeling can be altered or lost in neuropsychiatric disorders as well as in phenomena such as "automatic writing" whereby writing is attributed to an external source. Here, we employed suggestion in highly hypnotically suggestible participants to model various experiences of automatic writing during a sentence completion task. Results showed that the induction of hypnosis, without additional suggestion, was associated with a small but significant reduction of control, ownership, and awareness for writing. Targeted suggestions produced a double dissociation between thought and movement components of writing, for both feelings of control and ownership, and additionally, reduced awareness of writing. Overall, suggestion produced selective alterations in the control, ownership, and awareness of thought and motor components of writing, thus enabling key aspects of automatic writing, observed across different clinical and cultural settings, to be modelled.

  8. Formal Specification Based Automatic Test Generation for Embedded Network Systems

    Directory of Open Access Journals (Sweden)

    Eun Hye Choi

    2014-01-01

    Full Text Available Embedded systems have become increasingly connected and communicate with each other, forming large-scaled and complicated network systems. To make their design and testing more reliable and robust, this paper proposes a formal specification language called SENS and a SENS-based automatic test generation tool called TGSENS. Our approach is summarized as follows: (1 A user describes requirements of target embedded network systems by logical property-based constraints using SENS. (2 Given SENS specifications, test cases are automatically generated using a SAT-based solver. Filtering mechanisms to select efficient test cases are also available in our tool. (3 In addition, given a testing goal by the user, test sequences are automatically extracted from exhaustive test cases. We’ve implemented our approach and conducted several experiments on practical case studies. Through the experiments, we confirmed the efficiency of our approach in design and test generation of real embedded air-conditioning network systems.

  9. 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…

  10. 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

  11. 海空目标多尺度波峰最佳阈值自动搜索策略%Automatic search strategy for sea-sky target by multi-scale peak optimal threshold algorithm

    Institute of Scientific and Technical Information of China (English)

    景文博; 徐皓; 王晓曼; 姜会林

    2012-01-01

    针对海上低对比度低信噪比的条件下,能够精确快速搜索空域目标,提出了一种快速精确的海空目标多尺度波峰最佳阈值自动搜索策略:采用金字塔波门搜索和多尺度波峰阈值法,逐级减小搜索区域并对搜索域内图像进行分割,然后根据目标特征进行概率统计分析,确定最优目标,实现海空目标的自动搜索.实验结果表明,该算法在序列图像中的搜索定位平均误差为0.413像素并全部识别成功,较OTSU算法的2.61像素和最大熵阈值算法的3.1像素的误差,精确度大大提升.整幅图像搜索时间优于21.34 ms,满足海空目标自动搜索的精度和实时性的要求.%To search spatial domain target precisely and quickly in the condition of low contrast and low SNR, a new fast and accurate automatic search strategy for sea-sky target by multi-scale peak optimal threshold algorithm was proposed. Using the method of pyramid wave gate search and multi-scale peak threshold, the search area was gradually reduced and image segmentation was accomplished in this search area. Then, the probability and statistics according to the characteristics of the target was analysed to determine the optimum target and achieve automatic search for sea梥ky target. Experimental results show that the average error of searching and locating is 0.413 pixel and all identified with this algorithm in the image sequences, compared with 2.61 pixel of OTSU algorithm and 3.1 pixel of the maximum entropy threshold algorithm, the accuracy rises obviously. The whole image search time is less than 21.34 ms, which meets the requirements of the precision and real-time for automatically search of the sea-sky target.

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

    Science.gov (United States)

    Guo, Jing; Liu, Hui; Zheng, Jie

    2016-01-04

    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

  13. NBR1-mediated selective autophagy targets insoluble ubiquitinated protein aggregates in plant stress responses.

    Directory of Open Access Journals (Sweden)

    Jie Zhou

    Full Text Available Plant autophagy plays an important role in delaying senescence, nutrient recycling, and stress responses. Functional analysis of plant autophagy has almost exclusively focused on the proteins required for the core process of autophagosome assembly, but little is known about the proteins involved in other important processes of autophagy, including autophagy cargo recognition and sequestration. In this study, we report functional genetic analysis of Arabidopsis NBR1, a homolog of mammalian autophagy cargo adaptors P62 and NBR1. We isolated two nbr1 knockout mutants and discovered that they displayed some but not all of the phenotypes of autophagy-deficient atg5 and atg7 mutants. Like ATG5 and ATG7, NBR1 is important for plant tolerance to heat, oxidative, salt, and drought stresses. The role of NBR1 in plant tolerance to these abiotic stresses is dependent on its interaction with ATG8. Unlike ATG5 and ATG7, however, NBR1 is dispensable in age- and darkness-induced senescence and in resistance to a necrotrophic pathogen. A selective role of NBR1 in plant responses to specific abiotic stresses suggest that plant autophagy in diverse biological processes operates through multiple cargo recognition and delivery systems. The compromised heat tolerance of atg5, atg7, and nbr1 mutants was associated with increased accumulation of insoluble, detergent-resistant proteins that were highly ubiquitinated under heat stress. NBR1, which contains an ubiquitin-binding domain, also accumulated to high levels with an increasing enrichment in the insoluble protein fraction in the autophagy-deficient mutants under heat stress. These results suggest that NBR1-mediated autophagy targets ubiquitinated protein aggregates most likely derived from denatured or otherwise damaged nonnative proteins generated under stress conditions.

  14. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals.

    NARCIS (Netherlands)

    van Boxtel, R.; Toonen, P.W.; Verheul, M.; van Roekel, H.S.; Nijman, I.J.; Guryev, V.; Cuppen, E.

    2008-01-01

    BACKGROUND: The laboratory rat (Rattus norvegicus) is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is cur

  15. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals

    NARCIS (Netherlands)

    van Boxtel, Ruben; Toonen, Pim W; Verheul, Mark; van Roekel, Henk S; Nijman, Isaac J; Guryev, Victor; Cuppen, Edwin

    2008-01-01

    BACKGROUND: The laboratory rat (Rattus norvegicus) is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is cur

  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. Precipitation effects on the selection of suitable non-variant targets intended for atmospheric correction of satellite remotely sensed imagery

    Science.gov (United States)

    Themistocleous, Kyriacos; Hadjimitsis, Diofantos G.; Retalis, Adrianos; Chrysoulakis, Nektarios; Michaelides, Silas

    2013-09-01

    One of the most well-established atmospheric correction methods of satellite imagery is the use of the empirical line method using non-variant targets. Non-variant targets serve as pseudo-invariant targets since their reflectance values are stable across time. A recent adaptation of the empirical line method incorporates the use of ground reflectance measurements of selected non-variant targets. Most of the users are not aware of the existing conditions of the pseudo-invariant targets; i.e., whether they are dry or wet. Any omission of such effects may cause erroneous results; therefore, remote sensing users must be aware of such effects. This study assessed the effects of precipitation on five types of commonly located surfaces, including asphalt, concrete and sand, intended as pseudo-invariant targets for atmospheric correction. Spectroradiometric measurements were taken in wet and dry conditions to obtain the spectral signatures of the targets, from January 2010 to May 2011 (46 campaigns). An atmospheric correction of eleven Landsat TM/ETM + satellite images using the empirical line method was conducted. To identify the effects of precipitation, a comparison was conducted of the atmospheric path radiance component for wet and dry conditions. It was found that precipitation conditions such as rainfall affected the reflectance values of the surfaces, especially sand. Therefore, precipitation conditions need to be considered when using non-variant targets in atmospheric correction methods.

  18. Identification and Characterization of Genes Involved in Leishmania Pathogenesis: The Potential for Drug Target Selection

    Directory of Open Access Journals (Sweden)

    Robert Duncan

    2011-01-01

    Full Text Available Identifying and characterizing Leishmania donovani genes and the proteins they encode for their role in pathogenesis can reveal the value of this approach for finding new drug targets. Effective drug targets are likely to be proteins differentially expressed or required in the amastigote life cycle stage found in the patient. Several examples and their potential for chemotherapeutic disruption are presented. A pathway nearly ubiquitous in living cells targeted by anticancer drugs, the ubiquitin system, is examined. New findings in ubiquitin and ubiquitin-like modifiers in Leishmania show how disruption of those pathways could point to additional drug targets. The programmed cell death pathway, now recognized among protozoan parasites, is reviewed for some of its components and evidence that suggests they could be targeted for antiparasitic drug therapy. Finally, the endoplasmic reticulum quality control system is involved in secretion of many virulence factors. How disruptions in this pathway reduce virulence as evidence for potential drug targets is presented.

  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. 低空运动目标的多传感器自动识别和实时跟踪%Automatic identification and real-time tracking based on multiple sensors for low-altitude moving targets

    Institute of Scientific and Technical Information of China (English)

    张作楠; 刘国栋; 娄建

    2011-01-01

    This paper discussed a method for low altitude moving target detection and tracking in TV tracking system. In order to increase the ability of automatic tracking and anti-interferene, based on a variety of sensors and electronic measuring devices, such as acoustic sensors, image sensors and laser range finder,proposed a multi-sensor integrated automatic identification and real-time servo algorithm. Firstly located the target initially by the positive acoustic localization technology, secondly used the dynamic and static image features as well as the sound source characteristics of the target in target classification and recognition. According to video tracking and trajectory prediction algorithm, the desired target error signal control servo for precise tracking was used to control the servo mechanism to track precisely. Experiments show thattthe algorithm is simple and effective to achieve enough precision and reliability, and also validate the feasibility for multiple sensors being used in full-automatic intelligent tracking system.%讨论了一种用于低空运动目标检测和跟踪的电视跟踪系统.为了提高系统自动跟踪和抗干扰能力,基于声—光—电多种传感器和测量装置如声波传感器、图像传感器和激光测距仪等,提出一种多传感器综合的自动目标识别和实时跟踪算法.该方法将被动声定位技术用于目标初定位,结合目标图像动静态特征和目标声源特征用于目标的特征提取和自动识别,根据视频跟踪和轨迹预测算法,得出期望的目标误差信号控制伺服机构进行精确跟踪.实验结果表明该算法简捷有效、精度和可靠性达到要求,验证了多传感器应用于全自动智能跟踪系统的可行性.

  1. 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

  2. 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.

  3. Discovery: an interactive resource for the rational selection and comparison of putative drug target proteins in malaria

    Directory of Open Access Journals (Sweden)

    Odendaal Christiaan J

    2009-07-01

    Full Text Available Abstract Background Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub-Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties. Methods A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available. Results An in silico system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from Plasmodium falciparum. Conclusion The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties.

  4. Targeting the binding interface on a shared receptor subunit of a cytokine family enables the inhibition of multiple member cytokines with selectable target spectrum.

    Science.gov (United States)

    Nata, Toshie; Basheer, Asjad; Cocchi, Fiorenza; van Besien, Richard; Massoud, Raya; Jacobson, Steven; Azimi, Nazli; Tagaya, Yutaka

    2015-09-11

    The common γ molecule (γc) is a shared signaling receptor subunit used by six γc-cytokines. These cytokines play crucial roles in the differentiation of the mature immune system and are involved in many human diseases. Moreover, recent studies suggest that multiple γc-cytokines are pathogenically involved in a single disease, thus making the shared γc-molecule a logical target for therapeutic intervention. However, the current therapeutic strategies seem to lack options to treat such cases, partly because of the lack of appropriate neutralizing antibodies recognizing the γc and, more importantly, because of the inherent and practical limitations in the use of monoclonal antibodies. By targeting the binding interface of the γc and cytokines, we successfully designed peptides that not only inhibit multiple γc-cytokines but with a selectable target spectrum. Notably, the lead peptide inhibited three γc-cytokines without affecting the other three or non-γc-cytokines. Biological and mutational analyses of our peptide provide new insights to our current understanding on the structural aspect of the binding of γc-cytokines the γc-molecule. Furthermore, we provide evidence that our peptide, when conjugated to polyethylene glycol to gain stability in vivo, efficiently blocks the action of one of the target cytokines in animal models. Collectively, our technology can be expanded to target various combinations of γc-cytokines and thereby will provide a novel strategy to the current anti-cytokine therapies against immune, inflammatory, and malignant diseases.

  5. Automatic Fixture Planning

    Institute of Scientific and Technical Information of China (English)

    1999-01-01

    Fixture planning is a crucial problem in the field of fixture design. In this paper, the research scope and research methods of the computer-aided fixture planning are presented. Based on positioning principles of typical workparts, an ANN algorithm, namely Hopfield algorithm, is adopted for the automatic fixture planning. Also, this paper leads a deep research into the selection of positioning and clamping surfaces (or points) on workparts using positioning-clamping-surface-selecting rules and matrix evaluation of deterministic workpart positioning. In the end of this paper, the methods to select positioning and clamping elements from database and the layout algorithm to assemble the selected fixture elements into a tangible fixture are developed.

  6. Transient analysis mode participation for modal survey target mode selection using MSC/NASTRAN DMAP

    Science.gov (United States)

    Barnett, Alan R.; Ibrahim, Omar M.; Sullivan, Timothy L.; Goodnight, Thomas W.

    1994-01-01

    Many methods have been developed to aid analysts in identifying component modes which contribute significantly to component responses. These modes, typically targeted for dynamic model correlation via a modal survey, are known as target modes. Most methods used to identify target modes are based on component global dynamic behavior. It is sometimes unclear if these methods identify all modes contributing to responses important to the analyst. These responses are usually those in areas of hardware design concerns. One method used to check the completeness of target mode sets and identify modes contributing significantly to important component responses is mode participation. With this method, the participation of component modes in dynamic responses is quantified. Those modes which have high participation are likely modal survey target modes. Mode participation is most beneficial when it is used with responses from analyses simulating actual flight events. For spacecraft, these responses are generated via a structural dynamic coupled loads analysis. Using MSC/NASTRAN DMAP, a method has been developed for calculating mode participation based on transient coupled loads analysis results. The algorithm has been implemented to be compatible with an existing coupled loads methodology and has been used successfully to develop a set of modal survey target modes.

  7. Selecting Targets for Tumor Imaging: An Overview of Cancer-Associated Membrane Proteins

    Science.gov (United States)

    Boonstra, Martin C.; de Geus, Susanna W.L.; Prevoo, Hendrica A.J.M.; Hawinkels, Lukas J.A.C.; van de Velde, Cornelis J.H.; Kuppen, Peter J.K.; Vahrmeijer, Alexander L.; Sier, Cornelis F.M.

    2016-01-01

    Tumor targeting is a booming business: The global therapeutic monoclonal antibody market accounted for more than $78 billion in 2012 and is expanding exponentially. Tumors can be targeted with an extensive arsenal of monoclonal antibodies, ligand proteins, peptides, RNAs, and small molecules. In addition to therapeutic targeting, some of these compounds can also be applied for tumor visualization before or during surgery, after conjugation with radionuclides and/or near-infrared fluorescent dyes. The majority of these tumor-targeting compounds are directed against cell membrane-bound proteins. Various categories of targetable membrane-bound proteins, such as anchoring proteins, receptors, enzymes, and transporter proteins, exist. The functions and biological characteristics of these proteins determine their location and distribution on the cell membrane, making them more, or less, accessible, and therefore, it is important to understand these features. In this review, we evaluate the characteristics of cancer-associated membrane proteins and discuss their overall usability for cancer targeting, especially focusing on imaging applications.

  8. Automatic identification and real-time tracking based on multiple sensors for low-altitude moving targets%一种多传感器反直升机智能雷伺服跟踪系统

    Institute of Scientific and Technical Information of China (English)

    张作楠; 刘国栋; 王婷婷

    2011-01-01

    讨论一种基于多传感器的反直升机智能雷AHM(Anti-Helicopter Mine)系统.为了提高智能雷的全自动智能跟踪能力和打击精度,在传统的被动声探测技术的基础上,结合图像传感器的视觉信息和激光测距仪的深度信息,提出一种基于声-光-电多传感器联合的自动目标探测、识别、跟踪算法.首先将五元十字声源定位技术用于低空目标探测和初始定位,然后对目标进行图像处理与特征提取,最后基于图像特征的视觉伺服跟踪算法得出伺服机构的旋转角以实现精确跟踪.%Discussed a tracking system for anti-helicopter mine (AHM) tracking system based on multi-sensors, in order to increase the ability of automatic tracking and the higher firing accuracy. Based on the traditional passive acoustic localization technology, a multi-sensor integrated automatic detection and real-time tracking algorithm is proposed with a variety of sensors and electronic measuring devices, such as acoustic sensors, image sensors and laser range finder. Firstly the target is initially located by the positive acoustic localization technology, then attract the target image feature by image processing, According to based-on-image visual servoing algorithm, the desired target error signal for precise tracking is used to control the servo mechanism to track precisely.

  9. GABA A/Bz receptor subtypes as targets for selective drugs.

    Science.gov (United States)

    Da Settimo, F; Taliani, S; Trincavelli, M L; Montali, M; Martini, C

    2007-01-01

    The gamma-aminobutyric acid type A (GABA(A)) receptors are the major inhibitory neuronal receptors in the mammalian brain. Their activation by GABA opens the intrinsic ion channel, enabling chloride flux into the cell with subsequent hyperpolarization. Several GABA(A) receptor subunit isoforms have been cloned, the major isoform containing alpha, beta, and gamma subunits, and a regional heterogeneity associated with distinct physiological effects has been suggested. As a variety of allosteric ligands can modulate GABA-gated conductance changes through binding to distinct sites, the development of subtype-selective ligands may lead to the selective treatment of GABA system-associated pathology. In particular, the best characterized binding site is the benzodiazepine site (BzR), localized at the alpha/gamma subunit interface, in which the alpha subunit is the main determinant of BzR ligand action selectivity. The alpha1-containing BzR have been proposed to be responsible for the sedative action; the alpha2 and/or the alpha3 subtypes have been suggested to mediate the anxiolytic activity and the myorelaxation effects, and the alpha5 subtype has been associated with cognition processes. The discovery of alpha-selective subtype ligands may help in the specific treatment of anxiety, sleep disorders, convulsions and memory deficits with fewer side effects. Selectivity may be achieved by two approaches: selective affinity or selective efficacy. Selective affinity needs a compound to bind with a higher affinity to one receptor subtype compared with another, whereas subtype-selective efficacy relies on a compound binding to all subtypes, but having different efficacies at various subtypes. The status of BzR ligands, subdivided on the basis of their main chemical structural features, is reviewed in relation to structure-activity relationships which determine their affinity or efficacy selectivity for a certain BzR subtype.

  10. Receptor binding peptides for target-selective delivery of nanoparticles encapsulated drugs

    Directory of Open Access Journals (Sweden)

    Accardo A

    2014-03-01

    Full Text Available Antonella Accardo,1 Luigi Aloj,2 Michela Aurilio,2 Giancarlo Morelli,1 Diego Tesauro11Centro interuniversitario di Ricerca sui Peptidi Bioattivi (CIRPeB, Department of Pharmacy and Istituto di Biostrutture e Bioimmagini - Consiglio Nazionale delle Ricerche (IBB CNR, University of Naples “Federico II”, 2Department of Nuclear Medicine, Istituto Nazionale per lo Studio e la Cura dei Tumori, Fondazione “G. Pascale”, Napoli, ItalyAbstract: Active targeting by means of drug encapsulated nanoparticles decorated with targeting bioactive moieties represents the next frontier in drug delivery; it reduces drug side effects and increases the therapeutic index. Peptides, based on their chemical and biological properties, could have a prevalent role to direct drug encapsulated nanoparticles, such as liposomes, micelles, or hard nanoparticles, toward the tumor tissues. A considerable number of molecular targets for peptides are either exclusively expressed or overexpressed on both cancer vasculature and cancer cells. They can be classified into three wide categories: integrins; growth factor receptors (GFRs; and G-protein coupled receptors (GPCRs. Therapeutic agents based on nanovectors decorated with peptides targeting membrane receptors belonging to the GPCR family overexpressed by cancer cells are reviewed in this article. The most studied targeting membrane receptors are considered: somatostatin receptors; cholecystokinin receptors; receptors associated with the Bombesin like peptides family; luteinizing hormone-releasing hormone receptors; and neurotensin receptors. Nanovectors of different sizes and shapes (micelles, liposomes, or hard nanoparticles loaded with doxorubicin or other cytotoxic drugs and externally functionalized with natural or synthetic peptides are able to target the overexpressed receptors and are described based on their formulation and in vitro and in vivo behaviors.Keywords: receptors binding peptides, drug delivery

  11. Selecting target populations for ROPS retrofit programs in Pennsylvania and Vermont.

    Science.gov (United States)

    Yoder, A M; Sorensen, J A; Foster, F; Myers, M; Murphy, D; Cook, G; May, J; Jenkins, P

    2013-07-01

    Agriculture has the highest injury and fatality rates when compared with other U.S. industries, and tractor overturns remain the leading cause of agricultural fatalities. Rollover protection structures (ROPS) are the only proven devices to protect a tractor operator in the event of an overturn. These devices are 99% effective when used with a seatbelt. Nearly 49% of tractors in the U.S. are not equipped with a ROPS. Interventions such as social marketing, community awareness campaigns, and financial incentives have been directed at encouraging farmers to install ROPS on their unprotected tractors. The purpose of this study was to conduct similar comparisons of ROPS protection and readiness to retrofit in different segments of the Vermont and Pennsylvania farm communities. A telephone survey was used to collect data on ROPS prevalence, farm demographic characteristics, and farmer's stage of change relative to installing ROPS on farm tractors. Our data provide new and unique information on the prevalence of ROPS-equipped tractors relative to commodity, farm size, and a variety of other demographic variables. Extrapolating from these data, the commodities studied account for roughly 162,072 tractors across the two states. Of these, 85,927 (53%) do not have ROPS. Of these unprotected tractors, 77,203 are in Pennsylvania and 8,724 are in Vermont. Our other two research questions dealt with the farmer's stage of change and possible ways to segment this population. The stage of change portion of our work demonstrates that most Pennsylvania and Vermont farmers are not contemplating ROPS retrofitting in the near future. Since no major differences were found in the stage of change, the number of unprotected tractors was examined for each of the commodity groups. In Pennsylvania, 29% of all unprotected tractors were found on cash crop farms. This trend was even more apparent on smaller farms than large farms. This led to the selection of smaller cash crop farms as the target

  12. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals

    Directory of Open Access Journals (Sweden)

    van Roekel Henk S

    2008-10-01

    Full Text Available Abstract Background The laboratory rat (Rattus norvegicus is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive. Results As ENU-induced DNA damage is normally recognized by the mismatch repair (MMR system, we hypothesized that the effectiveness of the target-selected mutagenesis approach could be improved by using a MMR-deficient genetic background. Indeed, Msh6 knockout rats were found to be more sensitive to ENU treatment and the germ line mutation rate was boosted more than two-fold to 1 mutation per 585 kb. In addition, the molecular mutation spectrum was found to be changed in favor of generating knockout-type alleles by ~20%, resulting in an overall increase in efficiency of ~2.5 fold. The improved effectiveness was demonstrated by high throughput mutation discovery in 70 Mb of sequence in a set of only 310 mutant F1 rats. This resulted in the identification of 89 mutations of which four introduced a premature stopcodon and 64 resulted in amino acid changes. Conclusion Taken together, we show that the use of a MMR-deficient background considerably improves ENU-driven target-selected mutagenesis in the rat, thereby reducing animal use as well as screening costs. The use of a mismatch repair-deficient genetic background for improving mutagenesis and target-selected knockout efficiency is in principle applicable to any organism of interest.

  13. Improved generation of rat gene knockouts by target-selected mutagenesis in mismatch repair-deficient animals

    Science.gov (United States)

    van Boxtel, Ruben; Toonen, Pim W; Verheul, Mark; van Roekel, Henk S; Nijman, Isaac J; Guryev, Victor; Cuppen, Edwin

    2008-01-01

    Background The laboratory rat (Rattus norvegicus) is one of the preferred model organisms in physiological and pharmacological research, although the availability of specific genetic models, especially gene knockouts, is limited. N-ethyl-N-nitrosourea (ENU)-driven target-selected mutagenesis is currently the most successful method in rats, although it is still very laborious and expensive. Results As ENU-induced DNA damage is normally recognized by the mismatch repair (MMR) system, we hypothesized that the effectiveness of the target-selected mutagenesis approach could be improved by using a MMR-deficient genetic background. Indeed, Msh6 knockout rats were found to be more sensitive to ENU treatment and the germ line mutation rate was boosted more than two-fold to 1 mutation per 585 kb. In addition, the molecular mutation spectrum was found to be changed in favor of generating knockout-type alleles by ~20%, resulting in an overall increase in efficiency of ~2.5 fold. The improved effectiveness was demonstrated by high throughput mutation discovery in 70 Mb of sequence in a set of only 310 mutant F1 rats. This resulted in the identification of 89 mutations of which four introduced a premature stopcodon and 64 resulted in amino acid changes. Conclusion Taken together, we show that the use of a MMR-deficient background considerably improves ENU-driven target-selected mutagenesis in the rat, thereby reducing animal use as well as screening costs. The use of a mismatch repair-deficient genetic background for improving mutagenesis and target-selected knockout efficiency is in principle applicable to any organism of interest. PMID:18840264

  14. Integrating Enzymatic Self-Assembly and Mitochondria Targeting for Selectively Killing Cancer Cells without Acquired Drug Resistance.

    Science.gov (United States)

    Wang, Huaimin; Feng, Zhaoqianqi; Wang, Youzhi; Zhou, Rong; Yang, Zhimou; Xu, Bing

    2016-12-14

    Targeting organelles by modulating the redox potential of mitochondria is a promising approach to kill cancer cells that minimizes acquired drug resistance. However, it lacks selectivity because mitochondria perform essential functions for (almost) all cells. We show that enzyme-instructed self-assembly (EISA), a bioinspired molecular process, selectively generates the assemblies of redox modulators (e.g., triphenyl phosphinium (TPP)) in the pericellular space of cancer cells for uptake, which allows selectively targeting the mitochondria of cancer cells. The attachment of TPP to a pair of enantiomeric, phosphorylated tetrapeptides produces the precursors (L-1P or D-1P) that form oligomers. Upon dephosphorylation catalyzed by ectophosphatases (e.g., alkaline phosphatase (ALP)) overexpressed on cancer cells (e.g., Saos2), the oligomers self-assemble to form nanoscale assemblies only on the surface of the cancer cells. The cancer cells thus uptake these assemblies of TPP via endocytosis, mainly via a caveolae/raft-dependent pathway. Inside the cells, the assemblies of TPP-peptide conjugates escape from the lysosome, induce dysfunction of mitochondria to release cytochrome c, and result in cell death, while the controls (i.e., omitting TPP motif, inhibiting ALP, or removing phosphate trigger) hardly kill the Saos2 cells. Most importantly, the repeated stimulation of the cancers by the precursors, unexpectedly, sensitizes the cancer cells to the precursors. As the first example of the integration of subcellular targeting with cell targeting, this study validates the spatial control of the assemblies of nonspecific cytotoxic agents by EISA as a promising molecular process for selectively killing cancer cells without inducing acquired drug resistance.

  15. Targeted Multifunctional Nanoparticles cure and image Brain Tumors: Selective MRI Contrast Enhancement and Photodynamic Therapy

    Science.gov (United States)

    Kopelman, Raoul

    2008-03-01

    Aimed at targeted therapy and imaging of brain tumors, our approach uses targeted, multi-functional nano-particles (NP). A typical nano-particle contains a biologically inert, non-toxic matrix, biodegradable and bio-eliminable over a long time period. It also contains active components, such as fluorescent chemical indicators, photo-sensitizers, MRI contrast enhancement agents and optical imaging dyes. In addition, its surface contains molecular targeting units, e.g. peptides or antibodies, as well as a cloaking agent, to prevent uptake by the immune system, i.e. enabling control of the plasma residence time. These dynamic nano-platforms (DNP) contain contrast enhancement agents for the imaging (MRI, optical, photo-acoustic) of targeted locations, i.e. tumors. Added to this are targeted therapy agents, such as photosensitizers for photodynamic therapy (PDT). A simple protocol, for rats implanted with human brain cancer, consists of tail injection with DNPs, followed by 5 min red light illumination of the tumor region. It resulted in excellent cure statistics for 9L glioblastoma.

  16. 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

    2016-08-01

    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.

  17. ERP markers of target selection discriminate children with high vs. low working memory capacity

    Science.gov (United States)

    Shimi, Andria; Nobre, Anna Christina; Scerif, Gaia

    2015-01-01

    Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM) system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults’ selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children’s selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults’ selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc). However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the “adult time-window” related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children’s neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM performance in

  18. ERP markers of target selection discriminate children with high vs. low working memory capacity

    Directory of Open Access Journals (Sweden)

    Andria eShimi

    2015-11-01

    Full Text Available Selective attention enables enhancing a subset out of multiple competing items to maximize the capacity of our limited visual working memory (VWM system. Multiple behavioral and electrophysiological studies have revealed the cognitive and neural mechanisms supporting adults’ selective attention of visual percepts for encoding in VWM. However, research on children is more limited. What are the neural mechanisms involved in children’s selection of incoming percepts in service of VWM? Do these differ from the ones subserving adults’ selection? Ten-year-olds and adults used a spatial arrow cue to select a colored item for later recognition from an array of four colored items. The temporal dynamics of selection were investigated through EEG signals locked to the onset of the memory array. Both children and adults elicited significantly more negative activity over posterior scalp locations contralateral to the item to-be-selected for encoding (N2pc. However, this activity was elicited later and for longer in children compared to adults. Furthermore, although children as a group did not elicit a significant N2pc during the time-window in which N2pc was elicited in adults, the magnitude of N2pc during the adult time-window related to their behavioral performance during the later recognition phase of the task. This in turn highlights how children’s neural activity subserving attention during encoding relates to better subsequent VWM performance. Significant differences were observed when children were divided into groups of high vs. low VWM capacity as a function of cueing benefit. Children with large cue benefits in VWM capacity elicited an adult-like contralateral negativity following attentional selection of the to-be-encoded item, whereas children with low VWM capacity did not. These results corroborate the close coupling between selective attention and VWM from childhood and elucidate further the attentional mechanisms constraining VWM

  19. Cooperative interactions between CBP and TORC2 confer selectivity to CREB target gene expression

    DEFF Research Database (Denmark)

    Ravnskjær, Kim; Kester, Henri; Liu, Yi;

    2007-01-01

    , but have minimal effects on CRE-dependent transcription. Here, we show that the latent cytoplasmic coactivator TORC2 mediates target gene activation in response to cAMP signaling by associating with CBP/p300 and increasing its recruitment to a subset of CREB target genes. TORC2 is not activated in response...... to stress signals, however; and in its absence, P-CREB is unable to stimulate CRE-dependent transcription, due to a block in CBP recruitment. The effect of TORC2 on CBP/p300 promoter occupancy appears pivotal because a gain of function mutant CREB polypeptide with increased affinity for CBP restored CRE...

  20. 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

    juvenile males and hunter-killed adult females. In instances where disease infects a metapopulation and eradication is infeasible, a principle goal of management is to limit the spread of disease among infected animals. We map high-risk areas that are regularly used by potentially infectious hosts......-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......, in southwestern Manitoba, Canada. Distance to protected area was the most important covariate influencing resource selection and hunter-kill sites of elk (AICw = 1.00). Collared adult males (which are most likely to be infected with bovine tuberculosis (Mycobacterium bovis) and chronic wasting disease) rarely...

  1. 6-alkylsalicylates are selective Tip60 inhibitors and target the acetyl-CoA binding site

    NARCIS (Netherlands)

    Ghizzoni, Massimo; Wu, Jiang; Gao, Tielong; Haisma, Hidde J.; Dekker, Frank J.; Zheng, Y. George

    2012-01-01

    Histone acetyltransferases are important enzymes that regulate various cellular functions, such as epigenetic control of DNA transcription. Development of HAT inhibitors with high selectivity and potency will provide powerful mechanistic tools for the elucidation of the biological functions of HATs

  2. Development and experiment of automatic target spray control system used in orchard sprayer%果园喷雾机自动对靶喷雾控制系统研制与试验

    Institute of Scientific and Technical Information of China (English)

    许林云; 张昊天; 张海锋; 徐业勇; 徐铭铭; 蒋雪松; 张慧春; 贾志成

    2014-01-01

    In order to improve the utilization rate of pesticides and reduce the pesticide pollution to the environment, the control system of the automatic target spray was designed to focus on a Chinese low level of mechanization about the orchard sprayer and the invalid spray existed in the gap of fruit trees when the orchard sprayer sprayed with a continuous spray method. Whether the automatic target spray system sprayed to the fruit trees, depended on the detection distance between the orchard sprayer and the fruit trees by the application of distance measuring sensors and control program, which was installed on the GY8 caterpillar self-propelled orchard sprayer manufactured by Nantong Guangyi Mechanical & Electrical Co, Ltd. This paper compared the properties of three kinds of sensors which were MB7060 ultrasonic sensor, GP2Y0A710K0F infrared sensor and DT35-B15251 laser sensor, and tested the discernible spacing for the ultrasonic sensor and the laser sensor. The laser sensor was chosen as a detection device of the orchard sprayer for its high stability, fast response and good direction, while the other two sensors were abandoned for the following reasons that the infrared sensor was seriously affected by the sunshine, and the discernible spacing of ultrasonic sensor was too wide to satisfy the working conditions of the orchard sprayer. The parameters of the target range for spray trees could be adjusted in the system of the automatic target spray, based on different planted size (spacing in the rows and spacing between rows) of an orchard and the different travel speed of the orchard sprayer. The automatic target spray system could distinguish whether the fruit tree, or the gap between fruit trees and the gap in the canopies, so as to effectively control pests with the minimum dose of pesticide and the least environmental pollution. To ensure that the droplet could cover the whole canopy, the orchard sprayer must start to spray before the nozzle assembly reached the

  3. 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.

  4. Design, Characterization, and Lead Selection of Therapeutic miRNAs Targeting Huntingtin for Development of Gene Therapy for Huntington's Disease.

    Science.gov (United States)

    Miniarikova, Jana; Zanella, Ilaria; Huseinovic, Angelina; van der Zon, Tom; Hanemaaijer, Evelyn; Martier, Raygene; Koornneef, Annemart; Southwell, Amber L; Hayden, Michael R; van Deventer, Sander J; Petry, Harald; Konstantinova, Pavlina

    2016-03-22

    Huntington's disease (HD) is a neurodegenerative disorder caused by accumulation of CAG expansions in the huntingtin (HTT) gene. Hence, decreasing the expression of mutated HTT (mtHTT) is the most upstream approach for treatment of HD. We have developed HTT gene-silencing approaches based on expression cassette-optimized artificial miRNAs (miHTTs). In the first approach, total silencing of wild-type and mtHTT was achieved by targeting exon 1. In the second approach, allele-specific silencing was induced by targeting the heterozygous single-nucleotide polymorphism (SNP) rs362331 in exon 50 or rs362307 in exon 67 linked to mtHTT. The miHTT expression cassette was optimized by embedding anti-HTT target sequences in ten pri-miRNA scaffolds and their HTT knockdown efficacy, allele selectivity, passenger strand activity, and processing patterns were analyzed in vitro. Furthermore, three scaffolds expressing miH12 targeting exon 1 were incorporated in an adeno-associated viral serotype 5 (AAV5) vector and their HTT knock-down efficiency and pre-miHTT processing were compared in the humanized transgenic Hu128/21 HD mouse model. Our data demonstrate strong allele-selective silencing of mtHTT by miSNP50 targeting rs362331 and total HTT silencing by miH12 both in vitro and in vivo. Ultimately, we show that HTT knock-down efficiency and guide strand processing can be enhanced by using different cellular pri-miRNA scaffolds.

  5. 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.

  6. Proteasome activator complex PA28 identified as an accessible target in prostate cancer by in vivo selection of human antibodies

    Science.gov (United States)

    Sánchez-Martín, David; Martínez-Torrecuadrada, Jorge; Teesalu, Tambet; Sugahara, Kazuki N.; Alvarez-Cienfuegos, Ana; Ximénez-Embún, Pilar; Fernández-Periáñez, Rodrigo; Martín, M. Teresa; Molina-Privado, Irene; Ruppen-Cañás, Isabel; Blanco-Toribio, Ana; Cañamero, Marta; Cuesta, Ángel M.; Compte, Marta; Kremer, Leonor; Bellas, Carmen; Alonso-Camino, Vanesa; Guijarro-Muñoz, Irene; Sanz, Laura; Ruoslahti, Erkki; Alvarez-Vallina, Luis

    2013-01-01

    Antibody cancer therapies rely on systemically accessible targets and suitable antibodies that exert a functional activity or deliver a payload to the tumor site. Here, we present proof-of-principle of in vivo selection of human antibodies in tumor-bearing mice that identified a tumor-specific antibody able to deliver a payload and unveils the target antigen. By using an ex vivo enrichment process against freshly disaggregated tumors to purge the repertoire, in combination with in vivo biopanning at optimized phage circulation time, we have identified a human domain antibody capable of mediating selective localization of phage to human prostate cancer xenografts. Affinity chromatography followed by mass spectrometry analysis showed that the antibody recognizes the proteasome activator complex PA28. The specificity of soluble antibody was confirmed by demonstrating its binding to the active human PA28αβ complex. Whereas systemically administered control phage was confined in the lumen of blood vessels of both normal tissues and tumors, the selected phage spread from tumor vessels into the perivascular tumor parenchyma. In these areas, the selected phage partially colocalized with PA28 complex. Furthermore, we found that the expression of the α subunit of PA28 [proteasome activator complex subunit 1 (PSME1)] is elevated in primary and metastatic human prostate cancer and used anti-PSME1 antibodies to show that PSME1 is an accessible marker in mouse xenograft tumors. These results support the use of PA28 as a tumor marker and a potential target for therapeutic intervention in prostate cancer. PMID:23918357

  7. Lessons Learned: Dose Selection of Small Molecule-Targeted Oncology Drugs.

    Science.gov (United States)

    Bullock, Julie M; Rahman, Atiqur; Liu, Qi

    2016-06-01

    Evaluation of dose plays a critical role in a successful oncology development program. Typically for oncology agents, the first-in-man phase I dose-escalation trials are conducted to determine a maximum tolerated dose (MTD). This MTD is taken forward into subsequent trials to establish the safety and efficacy of the drug product. Although this approach was appropriate historically for cytotoxics, the application of MTD as the recommend phase II dose has been problematic for the newer small molecule-targeted oncology agents. Promising alternative approaches using dose and exposure exploration, including lessons learned from recent targeted oncology agent development and approvals, are summarized and discussed. Clin Cancer Res; 22(11); 2630-8. ©2016 AACR SEE ALL ARTICLES IN THIS CCR FOCUS SECTION, "NEW APPROACHES FOR OPTIMIZING DOSING OF ANTICANCER AGENTS".

  8. Selection and Training of Field Artillery Forward Observers: Methodologies for Improving Target Acquisition Skills

    Science.gov (United States)

    1979-07-01

    William J. Edens of McDonnell Douglas Automation Company provided invaluable assistance in conducting the statistical analyses used in the profile...22. SELECT AND OCGUPY OBStR - .12 .09 .05 .20 .5= 0 .20 0 .02 .07 .69 .02 .55 .23 .16 t VATIO POSTS. 23. OSERVE FROM A TANK- . .36 .05 .11 .05 .02 .18

  9. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors.

    Science.gov (United States)

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-09-15

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail.

  10. Regulation of locomotion and motoneuron trajectory selection and targeting by the Drosophila homolog of Olig family transcription factors

    Science.gov (United States)

    Oyallon, Justine; Apitz, Holger; Miguel-Aliaga, Irene; Timofeev, Katarina; Ferreira, Lauren; Salecker, Iris

    2012-01-01

    During the development of locomotion circuits it is essential that motoneurons with distinct subtype identities select the correct trajectories and target muscles. In vertebrates, the generation of motoneurons and myelinating glia depends on Olig2, one of the five Olig family bHLH transcription factors. We investigated the so far unknown function of the single Drosophila homolog Oli. Combining behavioral and genetic approaches, we demonstrate that oli is not required for gliogenesis, but plays pivotal roles in regulating larval and adult locomotion, and axon pathfinding and targeting of embryonic motoneurons. In the embryonic nervous system, Oli is primarily expressed in postmitotic progeny, and in particular, in distinct ventral motoneuron subtypes. oli mediates axonal trajectory selection of these motoneurons within the ventral nerve cord and targeting to specific muscles. Genetic interaction assays suggest that oli acts as part of a conserved transcription factor ensemble including Lim3, Islet and Hb9. Moreover, oli is expressed in postembryonic leg-innervating motoneuron lineages and required in glutamatergic neurons for walking. Finally, over-expression of vertebrate Olig2 partially rescues the walking defects of oli-deficient flies. Thus, our findings reveal a remarkably conserved role of Drosophila Oli and vertebrate family members in regulating motoneuron development, while the steps that require their function differ in detail. PMID:22796650

  11. Highly sensitive and selective analysis of widely targeted metabolomics using gas chromatography/triple-quadrupole mass spectrometry.

    Science.gov (United States)

    Tsugawa, Hiroshi; Tsujimoto, Yuki; Sugitate, Kuniyo; Sakui, Norihiro; Nishiumi, Shin; Bamba, Takeshi; Fukusaki, Eiichiro

    2014-01-01

    In metabolomics studies, gas chromatography coupled with time-of-flight or quadrupole mass spectrometry has frequently been used for the non-targeted analysis of hydrophilic metabolites. However, because the analytical platform employs the deconvolution method to extract single-metabolite information from co-eluted peaks and background noise, the extracted peak is artificial product depending on the mathematical parameters and is not completely compatible with the pure component obtained by analyzing a standard compound. Moreover, it has insufficient ability for quantitative metabolomics. Therefore, highly sensitive and selective methods capable of pure peak extraction without any complicated mathematical techniques are needed. For this purpose, we have developed a novel analytical method using gas chromatography coupled with triple-quadrupole mass spectrometry (GC-QqQ/MS). We developed a selected reaction monitoring (SRM) method to analyze the trimethylsilyl derivatives of 110 metabolites, using electron ionization. This methodology enables us to utilize two complementary techniques-non-targeted and widely targeted metabolomics in the same sample preparation protocol, which would facilitate the formulation or verification of novel hypotheses in biological sciences. The GC-QqQ/MS analysis can accurately identify a metabolite using multichannel SRM transitions and intensity ratios in the analysis of living organisms. In addition, our methodology offers a wide dynamic range, high sensitivity, and highly reproducible metabolite profiles, which will contribute to the biomarker discoveries and quality evaluations in biology, medicine, and food sciences.

  12. Selective targeting of HDAC1/2 elicits anticancer effects through Gli1 acetylation in preclinical models of SHH Medulloblastoma

    Science.gov (United States)

    Coni, Sonia; Mancuso, Anna Barbara; Di Magno, Laura; Sdruscia, Giulia; Manni, Simona; Serrao, Silvia Maria; Rotili, Dante; Spiombi, Eleonora; Bufalieri, Francesca; Petroni, Marialaura; Kusio-Kobialka, Monika; De Smaele, Enrico; Ferretti, Elisabetta; Capalbo, Carlo; Mai, Antonello; Niewiadomski, Pawel; Screpanti, Isabella; Di Marcotullio, Lucia; Canettieri, Gianluca

    2017-01-01

    SHH Medulloblastoma (SHH-MB) is a pediatric brain tumor characterized by an inappropriate activation of the developmental Hedgehog (Hh) signaling. SHH-MB patients treated with the FDA-approved vismodegib, an Hh inhibitor that targets the transmembrane activator Smoothened (Smo), have shown the rapid development of drug resistance and tumor relapse due to novel Smo mutations. Moreover, a subset of patients did not respond to vismodegib because mutations were localized downstream of Smo. Thus, targeting downstream Hh components is now considered a preferable approach. We show here that selective inhibition of the downstream Hh effectors HDAC1 and HDAC2 robustly counteracts SHH-MB growth in mouse models. These two deacetylases are upregulated in tumor and their knockdown inhibits Hh signaling and decreases tumor growth. We demonstrate that mocetinostat (MGCD0103), a selective HDAC1/HDAC2 inhibitor, is a potent Hh inhibitor and that its effect is linked to Gli1 acetylation at K518. Of note, we demonstrate that administration of mocetinostat to mouse models of SHH-MB drastically reduces tumor growth, by reducing proliferation and increasing apoptosis of tumor cells and prolongs mouse survival rate. Collectively, these data demonstrate the preclinical efficacy of targeting the downstream HDAC1/2-Gli1 acetylation in the treatment of SHH-MB. PMID:28276480

  13. Difference image analysis: Automatic kernel design using information criteria

    CERN Document Server

    Bramich, D M; Alsubai, K A; Bachelet, E; Mislis, D; Parley, N

    2015-01-01

    We present a selection of methods for automatically constructing an optimal kernel model for difference image analysis which require very few external parameters to control the kernel design. Each method consists of two components; namely, a kernel design algorithm to generate a set of candidate kernel models, and a model selection criterion to select the simplest kernel model from the candidate models that provides a sufficiently good fit to the target image. We restricted our attention to the case of solving for a spatially-invariant convolution kernel composed of delta basis functions, and we considered 19 different kernel solution methods including six employing kernel regularisation. We tested these kernel solution methods by performing a comprehensive set of image simulations and investigating how their performance in terms of model error, fit quality, and photometric accuracy depends on the properties of the reference and target images. We find that the irregular kernel design algorithm employing unreg...

  14. 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.

  15. 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.

  16. PLS-based and regularization-based methods for the selection of relevant variables in non-targeted metabolomics data

    Directory of Open Access Journals (Sweden)

    Renata Bujak

    2016-07-01

    Full Text Available Non-targeted metabolomics constitutes a part of systems biology and aims to determine many metabolites in complex biological samples. Datasets obtained in non-targeted metabolomics studies are multivariate and high-dimensional due to the sensitivity of mass spectrometry-based detection methods as well as complexity of biological matrices. 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. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA without and with multiple testing correction as well as least absolute shrinkage and selection operator (LASSO were tested and compared. For the RH study, OPLS-DA model built without multiple testing correction, selected 46 and 218 variables based on VIP criteria using Pareto and UV scaling, respectively. In the case of the PH study, 217 and 320 variables were selected based on VIP criteria using Pareto and UV scaling, respectively. In the RH study, OPLS-DA model built with multiple testing correction, selected 4 and 19 variables as statistically significant in terms of Pareto and UV scaling, respectively. For PH study, 14 and 18 variables were selected based on VIP criteria in terms of Pareto and UV scaling, respectively. Additionally, the concept and fundaments of the least absolute shrinkage and selection operator (LASSO with bootstrap procedure evaluating reproducibility of results, was demonstrated. In the RH and PH study, the LASSO selected 14 and 4 variables with reproducibility between 99.3% and 100%. However, apart from the popularity of PLS-DA and OPLS-DA methods in metabolomics, it should be highlighted that they do not control type I or type II error, but only arbitrarily establish a cut-off value for PLS-DA loadings

  17. CarPrice versus CarpRice: Word boundary ambiguity influences saccade target selection during the reading of Chinese sentences.

    Science.gov (United States)

    Yan, Ming; Kliegl, Reinhold

    2016-11-01

    As a contribution to a theoretical debate about the degree of high-level influences on saccade targeting during sentence reading, we investigated eye movements during the reading of structurally ambiguous Chinese character strings and examined whether parafoveal word segmentation could influence saccade-target selection. As expected, ambiguous strings took longer to process. More critically there were theoretically relevant interactions between ambiguity and launch site when first-fixation location and saccade amplitude served as dependent variables: Ambiguous strings in the parafovea triggered longer saccades and more rightward fixations for close launch sites than unambiguous ones; the reverse result was obtained for far launch sites. These crossover interactions indicate that parafoveal word segmentation influences saccade generation in Chinese and provide support of the hypothesis that high-level information can be involved in the decision about where to fixate next. (PsycINFO Database Record

  18. Effects of target distance on select biomechanical parameters in taekwondo roundhouse kick.

    Science.gov (United States)

    Falco, Coral; Molina-García, Javier; Alvarez, Octavio; Estevan, Isaac

    2013-11-01

    The aim of this study was to investigate the effects of target distance on temporal and impact force parameters that are important performance factors in taekwondo kicks. Forty-nine taekwondo athletes (age = 24.5 +/- 5.9 years; mass = 79.9 +/- 10.8 kg) were recruited: 13 male experts, 21 male novices, 8 female experts, and 6 female novices. Impact force, reaction time, and execution time were computed. Three-way repeated measure ANOVAs revealed significant 'distance' effect on impact force, reaction time, and execution time (p = 0.001). Comparisons between distance conditions revealed that taekwondo athletes kicked with higher impact force from short distance (17.6 +/- 7.5 N/kg) than from long distance (13.1 +/- 5.7 N/kg) (p < 0.001), had lower reaction time from short distance (498 +/- 90 ms) and normal distance (521 +/- 111 ms) than from long distance (602 +/- 121 ms) (p < 0.001), and had lower execution time from short distance (261 +/- 69 ms/m) than from normal distance (306 +/- 105 ms/m) or from long distance (350 +/- 106 ms/m) (p = 0.003 and p < 0.001, respectively). In conclusion, target distance affected the kick performance; as distance increases, impact force decreased and reaction time increased. Therefore, when reaction to a simple visual stimulus is needed, kicking from a long distance is not recommended, as longer time is required to respond.

  19. Application of Ultrasound to Selectively Localize Nanodroplets for Targeted Imaging and Therapy

    Directory of Open Access Journals (Sweden)

    Paul A. Dayton

    2006-07-01

    Full Text Available Lipid-coated perfluorocarbon nanodroplets are submicrometer-diameter liquid-filled droplets with proposed applications in molecularly targeted therapeutics and ultrasound (US imaging. Ultrasonic molecular imaging is unique in that the optimal application of these agents depends not only on the surface chemistry, but also on the applied US field, which can increase receptor-ligand binding and membrane fusion. Theory and experiments are combined to demonstrate the displacement of perfluorocarbon nanoparticles in the direction of US propagation, where a traveling US wave with a peak pressure on the order of megapascals and frequency in the megahertz range produces a particle translational velocity that is proportional to acoustic intensity and increases with increasing center frequency. Within a vessel with a diameter on the order of hundreds of micrometers or larger, particle velocity on the order of hundreds of micrometers per second is produced and the dominant mechanism for droplet displacement is shown to be bulk fluid streaming. A model for radiation force displacement of particles is developed and demonstrates that effective particle displacement should be feasible in the microvasculature. In a flowing system, acoustic manipulation of targeted droplets increases droplet retention. Additionally, we demonstrate the feasibility of US-enhanced particle internalization and therapeutic delivery.

  20. 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)

    Anne eGiersch

    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.

  1. Criteria for Selecting and Adjusting Ground-Motion Models for Specific Target Regions: Application to Central Europe and Rock Sites

    Science.gov (United States)

    Cotton, Fabrice; Scherbaum, Frank; Bommer, Julian J.; Bungum, Hilmar

    2006-04-01

    A vital component of any seismic hazard analysis is a model for predicting the expected distribution of ground motions at a site due to possible earthquake scenarios. The limited nature of the datasets from which such models are derived gives rise to epistemic uncertainty in both the median estimates and the associated aleatory variability of these predictive equations. In order to capture this epistemic uncertainty in a seismic hazard analysis, more than one ground-motion prediction equation must be used, and the tool that is currently employed to combine multiple models is the logic tree. Candidate ground-motion models for a logic tree should be selected in order to obtain the smallest possible suite of equations that can capture the expected range of possible ground motions in the target region. This is achieved by starting from a comprehensive list of available equations and then applying criteria for rejecting those considered inappropriate in terms of quality, derivation or applicability. Once the final list of candidate models is established, adjustments must be applied to achieve parameter compatibility. Additional adjustments can also be applied to remove the effect of systematic differences between host and target regions. These procedures are applied to select and adjust ground-motion models for the analysis of seismic hazard at rock sites in West Central Europe. This region is chosen for illustrative purposes particularly because it highlights the issue of using ground-motion models derived from small magnitude earthquakes in the analysis of hazard due to much larger events. Some of the pitfalls of extrapolating ground-motion models from small to large magnitude earthquakes in low seismicity regions are discussed for the selected target region.

  2. Automatic TLI recognition system, user`s guide

    Energy Technology Data Exchange (ETDEWEB)

    Lassahn, G.D.

    1997-02-01

    This report describes how to use an automatic target recognition system (version 14). In separate volumes are a general description of the ATR system, Automatic TLI Recognition System, General Description, and a programmer`s manual, Automatic TLI Recognition System, Programmer`s Guide.

  3. Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2 diabetes?

    Science.gov (United States)

    Patti, Mary-Elizabeth

    2010-08-01

    A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using the cannabinoid receptor inverse agonist rimonabant were successful in producing modest weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this drug into clinical practice. However, new data, presented by Tam and colleagues in this issue of the JCI, demonstrate that selective blockade of peripheral cannabinoid receptors may be a novel successful therapeutic approach.

  4. Automatic definition of targeted biological volumes for the radiotherapy applications; Definition automatique des volumes biologiques cibles pour les applications de radiotherapie

    Energy Technology Data Exchange (ETDEWEB)

    Hatt, M.; Visvikis, D. [LaTIM, U650 Inserm, 29 - Brest (France); Cheze-Le-Rest, C. [Service de medecine nucleaire, 29 - Brest (France); Pradier, O. [Service de radiotherapie, 29 - Brest (France)

    2009-10-15

    The proposed method: Fuzzy locally adaptive Bayesian (F.L.A.B.) showed its reliability and its precision on very complete collection of realistic simulated and real data. Its use in the context of radiotherapy allows to consider easily the studies implementation and scenari of dose painting or dose escalation, including in complex cases of heterogenous fixations. It is conceivable to apply F.L.A.B. on PET images with F.M.I.S.O. ({sup 18}F fluoro misonidazole) or F.L.T. (fluoro-L-thymidine) to complete the definition of the biological target volume. (N.C.)

  5. LuIII parvovirus selectively and efficiently targets, replicates in, and kills human glioma cells.

    Science.gov (United States)

    Paglino, Justin C; Ozduman, Koray; van den Pol, Anthony N

    2012-07-01

    Because productive infection by parvoviruses requires cell division and is enhanced by oncogenic transformation, some parvoviruses may have potential utility in killing cancer cells. To identify the parvovirus(es) with the optimal oncolytic effect against human glioblastomas, we screened 12 parvoviruses at a high multiplicity of infection (MOI). MVMi, MVMc, MVM-G17, tumor virus X (TVX), canine parvovirus (CPV), porcine parvovirus (PPV), rat parvovirus 1A (RPV1A), and H-3 were relatively ineffective. The four viruses with the greatest oncolytic activity, LuIII, H-1, MVMp, and MVM-G52, were tested for the ability, at a low MOI, to progressively infect the culture over time, causing cell death at a rate higher than that of cell proliferation. LuIII alone was effective in all five human glioblastomas tested. H-1 progressively infected only two of five; MVMp and MVM-G52 were ineffective in all five. To investigate the underlying mechanism of LuIII's phenotype, we used recombinant parvoviruses with the LuIII capsid replacing the MVMp capsid or with molecular alteration of the P4 promoter. The LuIII capsid enhanced efficient replication and oncolysis in MO59J gliomas cells; other gliomas tested required the entire LuIII genome to exhibit enhanced infection. LuIII selectively infected glioma cells over normal glial cells in vitro. In mouse models, human glioblastoma xenografts were selectively infected by LuIII when administered intratumorally; LuIII reduced tumor growth by 75%. LuIII also had the capacity to selectively infect subcutaneous or intracranial gliomas after intravenous inoculation. Intravenous or intracranial LuIII caused no adverse effects. Intracranial LuIII caused no infection of mature mouse neurons or glia in vivo but showed a modest infection of developing neurons.

  6. 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

  7. A recombinant fusion toxin based on enzymatic inactive C3bot1 selectively targets macrophages.

    Directory of Open Access Journals (Sweden)

    Lydia Dmochewitz

    Full Text Available BACKGROUND: The C3bot1 protein (~23 kDa from Clostridium botulinum ADP-ribosylates and thereby inactivates Rho. C3bot1 is selectively taken up into the cytosol of monocytes/macrophages but not of other cell types such as epithelial cells or fibroblasts. Most likely, the internalization occurs by a specific endocytotic pathway via acidified endosomes. METHODOLOGY/PRINCIPAL FINDINGS: Here, we tested whether enzymatic inactive C3bot1E174Q serves as a macrophage-selective transport system for delivery of enzymatic active proteins into the cytosol of such cells. Having confirmed that C3bot1E174Q does not induce macrophage activation, we used the actin ADP-ribosylating C2I (∼50 kDa from Clostridium botulinum as a reporter enzyme for C3bot1E174Q-mediated delivery into macrophages. The recombinant C3bot1E174Q-C2I fusion toxin was cloned and expressed as GST-protein in Escherichia coli. Purified C3bot1E174Q-C2I was recognized by antibodies against C2I and C3bot and showed C2I-specific enzyme activity in vitro. When applied to cultured cells C3bot1E174Q-C2I ADP-ribosylated actin in the cytosol of macrophages including J774A.1 and RAW264.7 cell lines as well as primary cultured human macrophages but not of epithelial cells. Together with confocal fluorescence microscopy experiments, the biochemical data indicate the selective uptake of a recombinant C3-fusion toxin into the cytosol of macrophages. CONCLUSIONS/SIGNIFICANCE: In summary, we demonstrated that C3bot1E174Q can be used as a delivery system for fast, selective and specific transport of enzymes into the cytosol of living macrophages. Therefore, C3-based fusion toxins can represent valuable molecular tools in experimental macrophage pharmacology and cell biology as well as attractive candidates to develop new therapeutic approaches against macrophage-associated diseases.

  8. Sejong Open Cluster Survey (SOS). 0. Target Selection and Data Analysis

    CERN Document Server

    Sung, Hwankyung; Bessell, Michael S; Kim, Jinyoung S; Hur, Hyenoh; Chun, Moo-Young; Park, Byeong-Gon

    2013-01-01

    Star clusters are superb astrophysical laboratories containing cospatial and coeval samples of stars with similar chemical composition. We have initiated the Sejong Open cluster Survey (SOS) - a project dedicated to providing homogeneous photometry of a large number of open clusters in the SAAO Johnson-Cousins' $UBVI$ system. To achieve our main goal, we have paid much attention to the observation of standard stars in order to reproduce the SAAO standard system. Many of our targets are relatively small, sparse clusters that escaped previous observations. As clusters are considered building blocks of the Galactic disk, their physical properties such as the initial mass function, the pattern of mass segregation, etc. give valuable information on the formation and evolution of the Galactic disk. The spatial distribution of young open clusters will be used to revise the local spiral arm structure of the Galaxy. In addition, the homogeneous data can also be used to test stellar evolutionary theory, especially conc...

  9. Targeting Phosphatidylserine on Apoptotic Cells with Phages and Peptides Selected from a Bacteriophage Display Library

    Directory of Open Access Journals (Sweden)

    Ruping Shao

    2007-11-01

    Full Text Available Phosphatidylserine (PS is a well-characterized biomarker for apoptosis. Ligands that bind to PS can be used for noninvasive imaging of therapy-induced cell death, particularly apoptosis. In this study, we screened a random 12-mer peptide phage library on liposomes prepared from PS. One clone displaying the peptide SVSVGMKPSPRP (designated as PS3-10 bound to PS approximately 4-fold better than its binding to phosphatidylcholine and 18-fold better than to bovine serum albumin in a solid-phase binding assay. In addition, the binding of the corresponding PS3-10 peptide to PS was significantly higher than that of a scrambled peptide. PS3-10 phages, but not a control 4-2-2 phage, bound to aged red blood cells that had PS exposed on their surface. Binding of PS3-10 phages and PS3-10 peptide to TRAIL-induced apoptotic DLD1 cells was 3.2 and 5.4 times higher than their binding to untreated viable cells, respectively. Significantly, immunohistochemical staining confirmed selective binding of PS3-10 phages to apoptotic cells. Our data suggest that panning of phage display libraries may allow the selection of suitable peptide ligands for apoptotic cells and that PS3-10 peptide may serve as a template for further development of molecular probes for in vitro and in vivo imaging of apoptosis.

  10. Selective targeting of mutant adenomatous polyposis coli (APC) in colorectal cancer.

    Science.gov (United States)

    Zhang, Lu; Theodoropoulos, Panayotis C; Eskiocak, Ugur; Wang, Wentian; Moon, Young-Ah; Posner, Bruce; Williams, Noelle S; Wright, Woodring E; Kim, Sang Bum; Nijhawan, Deepak; De Brabander, Jef K; Shay, Jerry W

    2016-10-19

    Mutations in the adenomatous polyposis coli (APC) gene are common in colorectal cancer (CRC), and more than 90% of those mutations generate stable truncated gene products. We describe a chemical screen using normal human colonic epithelial cells (HCECs) and a series of oncogenically progressed HCECs containing a truncated APC protein. With this screen, we identified a small molecule, TASIN-1 (truncated APC selective inhibitor-1), that specifically kills cells with APC truncations but spares normal and cancer cells with wild-type APC. TASIN-1 exerts its cytotoxic effects through inhibition of cholesterol biosynthesis. In vivo administration of TASIN-1 inhibits tumor growth of CRC cells with truncated APC but not APC wild-type CRC cells in xenograft models and in a genetically engineered CRC mouse model with minimal toxicity. TASIN-1 represents a potential therapeutic strategy for prevention and intervention in CRC with mutant APC.

  11. 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.

  12. 农业自动化喷雾机械标靶害虫自动识别系统的研究%Research on Automatic Identification System of Target Pests in Agricultural Automation Spraying Machine

    Institute of Scientific and Technical Information of China (English)

    张震; 高雄; 陈铁英; 王海超

    2016-01-01

    农业喷雾对象的识别和定位是农业自动化喷雾机械研究中的核心技术之一. 对病虫害甘蓝进行精准喷洒农药,实现病虫害准确自动识别成为关键. 为此,利用机器视觉的欧氏距离甘蓝夜蛾虫害自动识别检测系统,结合由Qualityspec 光谱仪组成的光谱成像系统,对甘蓝正常叶片和遭受甘蓝夜蛾虫害的甘蓝叶片的颜色特征和光谱特征进行分析,并采用机器视觉分割阈值选取中的Otsu算法和自适应波段选择方法提取出了颜色差异的最佳几何阈值和两种叶片的特征波段. 试验结果表明:综合机器视觉和光谱技术能够实现甘蓝夜蛾虫害的自动且准确的识别,准确率可达94%. 因此,建立机器视觉和光谱技术综合识别体系,可为农作物病虫害自动防治喷雾机器人的研制奠定基础,以达到农作物病虫害实时识别和及时治理的目的.%The spray object recognition and localization is one of the core technology of automatic spray mechanization re -search .For precision spraying pesticide plant diseases and insect pests of cabbage , the accurate and automatic identifica-tion of plant diseases and insect pests of cabbage becomes the key .Therefore , using machine vision automatic identifica-tion of the Euclidean distance of cabbage moth pests detection system , combined with spectral imaging system composed of qualityspec spectrometer , Cabbage normal blade and suffer from the cabbage moth pests of cabbage leaf color features and spectral characteristics were analyzed .The best geometric threshold of color difference and characteristic bands of two kinds of leaves were extracted , using the Otsu threshold value image segmentation algorithm and adaptive band selection method.The test results show that the technology compositing image processing with spectrum can realize automatic and accurate identification of Cabbage moth pests , accuracy reaching 94%.Therefore, the establishment of

  13. 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.

  14. 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.

  15. The Target Set Selection Problem on Cycle Permutation Graphs, Generalized Petersen Graphs and Torus Cordalis

    CERN Document Server

    Chiang, Chun-Ying; Huang, Wei-Ting; 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. In a a viral marketing setting, social networks are modeled by graphs with potential customers of a new product as vertices and friend relationships as edges, where each vertex $v$ is assigned a threshold value $\\theta(v)$. The thresholds represent the different latent tendencies of customers (vertices) to buy the new product when their friend (neighbors) do. Consider a repetitive process on social network $(G,\\theta)$ where each vertex $v$ is associated with two states, active and inactive, which indicate whether $v$ is persuaded into buying the new product. Suppose we are given a target set $S\\subseteq V(G)$. Initially, all vertices in $G$ are inactive. At time step 0, we choose all vertices in $S$ to become active. Then, at every time step $t>0$, all vertices that were active in time step $t-1$ remain active, and we activate any vertex $v$ if at leas...

  16. Visual working memory modulates low-level saccade target selection: evidence from rapidly generated saccades in the global effect paradigm.

    Science.gov (United States)

    Hollingworth, Andrew; Matsukura, Michi; Luck, Steven J

    2013-11-04

    In three experiments, we examined the influence of visual working memory (VWM) on the metrics of saccade landing position in a global effect paradigm. Participants executed a saccade to the more eccentric object in an object pair appearing on the horizontal midline, to the left or right of central fixation. While completing the saccade task, participants maintained a color in VWM for an unrelated memory task. Either the color of the saccade target matched the memory color (target match), the color of the distractor matched the memory color (distractor match), or the colors of neither object matched the memory color (no match). In the no-match condition, saccades tended to land at the midpoint between the two objects: the global, or averaging, effect. However, when one of the two objects matched VWM, the distribution of landing position shifted toward the matching object, both for target match and for distractor match. VWM modulation of landing position was observed even for the fastest quartile of saccades, with a mean latency as low as 112 ms. Effects of VWM on such rapidly generated saccades, with latencies in the express-saccade range, indicate that VWM interacts with the initial sweep of visual sensory processing, modulating perceptual input to oculomotor systems and thereby biasing oculomotor selection. As a result, differences in memory match produce effects on landing position similar to the effects generated by differences in physical salience.

  17. 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.

  18. Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity

    Science.gov (United States)

    Bao, Bin; Mitrea, Cristina; Wijesinghe, Priyanga; Marchetti, Luca; Girsch, Emily; Farr, Rebecca L.; Boerner, Julie L; Mohammad, Ramzi; Dyson, Greg; Terlecky, Stanley R.; Bollig-Fischer, Aliccia

    2017-01-01

    Among breast cancer patients, those diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or the HER2 oncogene; therefore, TNBC lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against TNBC has been put forth based on estimates that 30–60% of TNBC express high levels of EGFR. However, results from clinical trials testing EGFR inhibitors, alone or in combination with cytotoxic chemotherapy, did not improve patient outcomes. Results herein offer an explanation as to why EGFR inhibitors failed TNBC patients and support how combining a select antioxidant and an EGFR-specific small molecule kinase inhibitor (SMKI) could be an effective, novel therapeutic strategy. Treatment with CAT-SKL—a re-engineered protein form of the antioxidant enzyme catalase—inhibited cancer stem-like cells (CSCs), and treatment with the EGFR-specific SMKI erlotinib inhibited non-CSCs. Thus, combining the antioxidant CAT-SKL with erlotinib targeted both CSCs and bulk cancer cells in cultures of EGFR-expressing TNBC-derived cells. We also report evidence that the mechanism for CAT-SKL inhibition of CSCs may depend on antioxidant-induced downregulation of a short alternative mRNA splicing variant of the methyl-CpG binding domain 2 gene, isoform MBD2c. PMID:28281569

  19. Selective Targeting of a Disease-Related Conformational Isoform of Macrophage Migration Inhibitory Factor Ameliorates Inflammatory Conditions.

    Science.gov (United States)

    Thiele, Michael; Kerschbaumer, Randolf J; Tam, Frederick W K; Völkel, Dirk; Douillard, Patrice; Schinagl, Alexander; Kühnel, Harald; Smith, Jennifer; McDaid, John P; Bhangal, Gurjeet; Yu, Mei-Ching; Pusey, Charles D; Cook, H Terence; Kovarik, Josef; Magelky, Erica; Bhan, Atul; Rieger, Manfred; Mudde, Geert C; Ehrlich, Hartmut; Jilma, Bernd; Tilg, Herbert; Moschen, Alexander; Terhorst, Cox; Scheiflinger, Friedrich

    2015-09-01

    Macrophage migration inhibitory factor (MIF), a proinflammatory cytokine and counterregulator of glucocorticoids, is a potential therapeutic target. MIF is markedly different from other cytokines because it is constitutively expressed, stored in the cytoplasm, and present in the circulation of healthy subjects. Thus, the concept of targeting MIF for therapeutic intervention is challenging because of the need to neutralize a ubiquitous protein. In this article, we report that MIF occurs in two redox-dependent conformational isoforms. We show that one of the two isoforms of MIF, that is, oxidized MIF (oxMIF), is specifically recognized by three mAbs directed against MIF. Surprisingly, oxMIF is selectively expressed in the plasma and on the cell surface of immune cells of patients with different inflammatory diseases. In patients with acute infections or chronic inflammation, oxMIF expression correlated with inflammatory flare-ups. In addition, anti-oxMIF mAbs alleviated disease severity in mouse models of acute and chronic enterocolitis and improved, in synergy with glucocorticoids, renal function in a rat model of crescentic glomerulonephritis. We conclude that oxMIF represents the disease-related isoform of MIF; oxMIF is therefore a new diagnostic marker for inflammation and a relevant target for anti-inflammatory therapy.

  20. Treating triple negative breast cancer cells with erlotinib plus a select antioxidant overcomes drug resistance by targeting cancer cell heterogeneity.

    Science.gov (United States)

    Bao, Bin; Mitrea, Cristina; Wijesinghe, Priyanga; Marchetti, Luca; Girsch, Emily; Farr, Rebecca L; Boerner, Julie L; Mohammad, Ramzi; Dyson, Greg; Terlecky, Stanley R; Bollig-Fischer, Aliccia

    2017-03-10

    Among breast cancer patients, those diagnosed with the triple-negative breast cancer (TNBC) subtype have the worst prog-nosis. TNBC does not express estrogen receptor-alpha, progesterone receptor, or the HER2 oncogene; therefore, TNBC lacks targets for molecularly-guided therapies. The concept that EGFR oncogene inhibitor drugs could be used as targeted treatment against TNBC has been put forth based on estimates that 30-60% of TNBC express high levels of EGFR. However, results from clinical trials testing EGFR inhibitors, alone or in combination with cytotoxic chemotherapy, did not improve patient outcomes. Results herein offer an explanation as to why EGFR inhibitors failed TNBC patients and support how combining a select antioxidant and an EGFR-specific small molecule kinase inhibitor (SMKI) could be an effective, novel therapeutic strategy. Treatment with CAT-SKL-a re-engineered protein form of the antioxidant enzyme catalase-inhibited cancer stem-like cells (CSCs), and treatment with the EGFR-specific SMKI erlotinib inhibited non-CSCs. Thus, combining the antioxidant CAT-SKL with erlotinib targeted both CSCs and bulk cancer cells in cultures of EGFR-expressing TNBC-derived cells. We also report evidence that the mechanism for CAT-SKL inhibition of CSCs may depend on antioxidant-induced downregulation of a short alternative mRNA splicing variant of the methyl-CpG binding domain 2 gene, isoform MBD2c.

  1. 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.

  2. Identification of a Selective G1-Phase Benzimidazolone Inhibitor by a Senescence-Targeted Virtual Screen Using Artificial Neural Networks

    Directory of Open Access Journals (Sweden)

    Alan E. Bilsland

    2015-09-01

    Full Text Available Cellular senescence is a barrier to tumorigenesis in normal cells, and tumor cells undergo senescence responses to genotoxic stimuli, which is a potential target phenotype for cancer therapy. However, in this setting, mixed-mode responses are common with apoptosis the dominant effect. Hence, more selective senescence inducers are required. Here we report a machine learning–based in silico screen to identify potential senescence agonists. We built profiles of differentially affected biological process networks from expression data obtained under induced telomere dysfunction conditions in colorectal cancer cells and matched these to a panel of 17 protein targets with confirmatory screening data in PubChem. We trained a neural network using 3517 compounds identified as active or inactive against these targets. The resulting classification model was used to screen a virtual library of ~2M lead-like compounds. One hundred and forty-seven virtual hits were acquired for validation in growth inhibition and senescence-associated β-galactosidase assays. Among the found hits, a benzimidazolone compound, CB-20903630, had low micromolar IC50 for growth inhibition of HCT116 cells and selectively induced senescence-associated β-galactosidase activity in the entire treated cell population without cytotoxicity or apoptosis induction. Growth suppression was mediated by G1 blockade involving increased p21 expression and suppressed cyclin B1, CDK1, and CDC25C. In addition, the compound inhibited growth of multicellular spheroids and caused severe retardation of population kinetics in long-term treatments. Preliminary structure-activity and structure clustering analyses are reported, and expression analysis of CB-20903630 against other cell cycle suppressor compounds suggested a PI3K/AKT-inhibitor–like profile in normal cells, with different pathways affected in cancer cells.

  3. 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

  4. The Endosymbiotic Bacterium Wolbachia Selectively Kills Male Hosts by Targeting the Masculinizing Gene.

    Directory of Open Access Journals (Sweden)

    Takahiro Fukui

    2015-07-01

    Full Text Available Pathogens are known to manipulate the reproduction and development of their hosts for their own benefit. Wolbachia is an endosymbiotic bacterium that infects a wide range of insect species. Wolbachia is known as an example of a parasite that manipulates the sex of its host's progeny. Infection of Ostrinia moths by Wolbachia causes the production of all-female progeny, however, the mechanism of how Wolbachia accomplishes this male-specific killing is unknown. Here we show for the first time that Wolbachia targets the host masculinizing gene of Ostrinia to accomplish male-killing. We found that Wolbachia-infected O. furnacalis embryos do not express the male-specific splice variant of doublesex, a gene which acts at the downstream end of the sex differentiation cascade, throughout embryonic development. Transcriptome analysis revealed that Wolbachia infection markedly reduces the mRNA level of Masc, a gene that encodes a protein required for both masculinization and dosage compensation in the silkworm Bombyx mori. Detailed bioinformatic analysis also elucidated that dosage compensation of Z-linked genes fails in Wolbachia-infected O. furnacalis embryos, a phenomenon that is extremely similar to that observed in Masc mRNA-depleted male embryos of B. mori. Finally, injection of in vitro transcribed Masc cRNA into Wolbachia-infected embryos rescued male progeny. Our results show that Wolbachia-induced male-killing is caused by a failure of dosage compensation via repression of the host masculinizing gene. Our study also shows a novel strategy by which a pathogen hijacks the host sex determination cascade.

  5. Development of a Genus-Specific Antigen Capture ELISA for Orthopoxviruses - Target Selection and Optimized Screening.

    Directory of Open Access Journals (Sweden)

    Daniel Stern

    Full Text Available Orthopoxvirus species like cowpox, vaccinia and monkeypox virus cause zoonotic infections in humans worldwide. Infections often occur in rural areas lacking proper diagnostic infrastructure as exemplified by monkeypox, which is endemic in Western and Central Africa. While PCR detection requires demanding equipment and is restricted to genome detection, the evidence of virus particles can complement or replace PCR. Therefore, an easily distributable and manageable antigen capture enzyme-linked immunosorbent assay (ELISA for the detection of orthopoxviruses was developed to facilitate particle detection. By comparing the virus particle binding properties of polyclonal antibodies developed against surface-exposed attachment or fusion proteins, the surface protein A27 was found to be a well-bound, highly immunogenic and exposed target for antibodies aiming at virus particle detection. Subsequently, eight monoclonal anti-A27 antibodies were generated and characterized by peptide epitope mapping and surface plasmon resonance measurements. All antibodies were found to bind with high affinity to two epitopes at the heparin binding site of A27, toward either the N- or C-terminal of the crucial KKEP-segment of A27. Two antibodies recognizing different epitopes were implemented in an antigen capture ELISA. Validation showed robust detection of virus particles from 11 different orthopoxvirus isolates pathogenic to humans, with the exception of MVA, which is apathogenic to humans. Most orthopoxviruses could be detected reliably for viral loads above 1 × 103 PFU/mL. To our knowledge, this is the first solely monoclonal and therefore reproducible antibody-based antigen capture ELISA able to detect all human pathogenic orthopoxviruses including monkeypox virus, except variola virus which was not included. Therefore, the newly developed antibody-based assay represents important progress towards feasible particle detection of this important genus of viruses.

  6. The Endosymbiotic Bacterium Wolbachia Selectively Kills Male Hosts by Targeting the Masculinizing Gene.

    Science.gov (United States)

    Fukui, Takahiro; Kawamoto, Munetaka; Shoji, Keisuke; Kiuchi, Takashi; Sugano, Sumio; Shimada, Toru; Suzuki, Yutaka; Katsuma, Susumu

    2015-07-01

    Pathogens are known to manipulate the reproduction and development of their hosts for their own benefit. Wolbachia is an endosymbiotic bacterium that infects a wide range of insect species. Wolbachia is known as an example of a parasite that manipulates the sex of its host's progeny. Infection of Ostrinia moths by Wolbachia causes the production of all-female progeny, however, the mechanism of how Wolbachia accomplishes this male-specific killing is unknown. Here we show for the first time that Wolbachia targets the host masculinizing gene of Ostrinia to accomplish male-killing. We found that Wolbachia-infected O. furnacalis embryos do not express the male-specific splice variant of doublesex, a gene which acts at the downstream end of the sex differentiation cascade, throughout embryonic development. Transcriptome analysis revealed that Wolbachia infection markedly reduces the mRNA level of Masc, a gene that encodes a protein required for both masculinization and dosage compensation in the silkworm Bombyx mori. Detailed bioinformatic analysis also elucidated that dosage compensation of Z-linked genes fails in Wolbachia-infected O. furnacalis embryos, a phenomenon that is extremely similar to that observed in Masc mRNA-depleted male embryos of B. mori. Finally, injection of in vitro transcribed Masc cRNA into Wolbachia-infected embryos rescued male progeny. Our results show that Wolbachia-induced male-killing is caused by a failure of dosage compensation via repression of the host masculinizing gene. Our study also shows a novel strategy by which a pathogen hijacks the host sex determination cascade.

  7. 手持显控终端的目标标牌自动布局算法%An automatic placement algorithm of label plates of targets for handheld display and control terminal

    Institute of Scientific and Technical Information of China (English)

    沈静波; 刘扬; 牛洁

    2012-01-01

    针对雷达手持显控终端显示屏幕小、目标标牌和点航迹相互重叠影像用户识别的问题,本文提出了一种目标标牌自动布局算法,通过旋转布局的方式可以快速实时地计算标牌位置,在保证标牌靠近目标航迹的基础上,充分避免标牌之间以及标牌和航迹点之间的重叠发生。该算法可以适应雷达不同显示模式的需求,支持雷达常用干预操作。%The screen of the display and control terminal is small, and the label plates, plots and tracks of the targets are overlapped so that the users can hardly identify them. Therefore, an automatic placement algorithm of the label plates of the targets is proposed to solve the problem above. The positions of the label plates can be calculated rapidly and real-timely through the rotating placement. Make sure that the label plates are close to the target tracks, on the basis of which the overlap among the label plates and between the label plates and the tracks is avoided to the full. The algorithm can adapt to the needs of different radar display modes, supporting the common intervention operations.

  8. Selective targeting of the BRG/PB1 bromodomains impairs embryonic and trophoblast stem cell maintenance.

    Science.gov (United States)

    Fedorov, Oleg; Castex, Josefina; Tallant, Cynthia; Owen, Dafydd R; Martin, Sarah; Aldeghi, Matteo; Monteiro, Octovia; Filippakopoulos, Panagis; Picaud, Sarah; Trzupek, John D; Gerstenberger, Brian S; Bountra, Chas; Willmann, Dominica; Wells, Christopher; Philpott, Martin; Rogers, Catherine; Biggin, Philip C; Brennan, Paul E; Bunnage, Mark E; Schüle, Roland; Günther, Thomas; Knapp, Stefan; Müller, Susanne

    2015-11-01

    Mammalian SWI/SNF [also called Brg/Brahma-associated factors (BAFs)] are evolutionarily conserved chromatin-remodeling complexes regulating gene transcription programs during development and stem cell differentiation. BAF complexes contain an ATP (adenosine 5'-triphosphate)-driven remodeling enzyme (either BRG1 or BRM) and multiple protein interaction domains including bromodomains, an evolutionary conserved acetyl lysine-dependent protein interaction motif that recruits transcriptional regulators to acetylated chromatin. We report a potent and cell active protein interaction inhibitor, PFI-3, that selectively binds to essential BAF bromodomains. The high specificity of PFI-3 was achieved on the basis of a novel binding mode of a salicylic acid head group that led to the replacement of water molecules typically maintained in other bromodomain inhibitor complexes. We show that exposure of embryonic stem cells to PFI-3 led to deprivation of stemness and deregulated lineage specification. Furthermore, differentiation of trophoblast stem cells in the presence of PFI-3 was markedly enhanced. The data present a key function of BAF bromodomains in stem cell maintenance and differentiation, introducing a novel versatile chemical probe for studies on acetylation-dependent cellular processes controlled by BAF remodeling complexes.

  9. 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.

  10. 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.

  11. Selective inhibition of dipeptidyl peptidase 4 by targeting a substrate-specific secondary binding site.

    Science.gov (United States)

    Kühn-Wache, Kerstin; Bär, Joachim W; Hoffmann, Torsten; Wolf, Raik; Rahfeld, Jens-Ulrich; Demuth, Hans-Ulrich

    2011-03-01

    Dipeptidyl peptidase 4/CD26 (DP4) is a multifunctional serine protease liberating dipeptide from the N-terminus of (oligo)peptides which can modulate the activity of these peptides. The enzyme is involved in physiological processes such as blood glucose homeostasis and immune response. DP4 substrate specificity is characterized in detail using synthetic dipeptide derivatives. The specificity constant k(cat)/K(m) strongly depends on the amino acid in P₁-position for proline, alanine, glycine and serine with 5.0 x 10⁵ M⁻¹ s⁻¹, 1.8 x 10⁴ M⁻¹ s⁻¹, 3.6 x 10² M⁻¹ s⁻¹, 1.1 x 10² M⁻¹ s⁻¹, respectively. By contrast, kinetic investigation of larger peptide substrates yields a different pattern. The specific activity of DP4 for neuropeptide Y (NPY) cleavage comprising a proline in P₁-position is the same range as the k(cat)/K(m) values of NPY derivatives containing alanine or serine in P₁-position with 4 x 10⁵ M⁻¹ s⁻¹, 9.5 x 10⁵ M⁻¹ s⁻¹ and 2.1 x 10⁵ M⁻¹ s⁻¹, respectively. The proposed existence of an additional binding region outside the catalytic center is supported by measurements of peptide substrates with extended chain length. This 'secondary' binding site interaction depends on the amino acid sequence in P₄'-P₈'-position. Interactions with this binding site could be specifically blocked for substrates of the GRF/glucagon peptide family. By contrast, substrates not belonging to this peptide family and dipeptide derivative substrates that only bind to the catalytic center of DP4 were not inhibited. This more selective inhibition approach allows, for the first time, to distinguish between substrate families by substrate-discriminating inhibitors.

  12. Ligand-directed functional selectivity at the mu opioid receptor revealed by label-free integrative pharmacology on-target.

    Directory of Open Access Journals (Sweden)

    Megan Morse

    Full Text Available Development of new opioid drugs that provide analgesia without producing dependence is important for pain treatment. Opioid agonist drugs exert their analgesia effects primarily by acting at the mu opioid receptor (MOR sites. High-resolution differentiation of opioid ligands is crucial for the development of new lead drug candidates with better tolerance profiles. Here, we use a label-free integrative pharmacology on-target (iPOT approach to characterize the functional selectivity of a library of known opioid ligands for the MOR. This approach is based on the ability to detect dynamic mass redistribution (DMR arising from the activation of the MOR in living cells. DMR assays were performed in HEK-MOR cells with and without preconditioning with probe molecules using label-free resonant waveguide grating biosensors, wherein the probe molecules were used to modify the activity of specific signaling proteins downstream the MOR. DMR signals obtained were then translated into high resolution heat maps using similarity analysis based on a numerical matrix of DMR parameters. Our data indicate that the iPOT approach clearly differentiates functional selectivity for distinct MOR signaling pathways among different opioid ligands, thus opening new avenues to discover and quantify the functional selectivity of currently used and novel opioid receptor drugs.

  13. 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

  14. 卷烟生产联合工房火灾自动报警探测器选择%Selection of Automatic Fire Alarm Detector for Cigarette Manufacturing Joint Workshop

    Institute of Scientific and Technical Information of China (English)

    金超

    2015-01-01

    通过分析卷烟生产联合工房内制丝车间、卷接包车间、高架库等不同区域的建筑空间、生产环境以及对火灾自动报警系统的要求,结合工程设计及使用实际情况,探讨不同类型的火灾探测器在各生产区域使用的优劣及适用性,并提出卷烟生产联合工房火灾自动报警探测器选择方案。%By analysis on the architectural spaces, manufacturing environment and requirements for the automatic fire alarm system for the tobacco cutting workshop, fabricating and packing workshop, high-rack warehouse and other areas of the cigarette manufacturing joint workshop, the advantages, disadvantages and suitability of different fire detectors for different manufacturing areas are discussed on the basis of the engineering design and actual utilization conditions, and the selection plan for the automatic fire alarm detector for the cigarette manufacturing joint workshop is proposed.

  15. 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

  16. Applying new hybrid method of analytical hierarchy process, Monte Carlo Simulation and PROMETHEE to prioritize and selecting appropriate target market

    Directory of Open Access Journals (Sweden)

    Amir Kariznoee

    2015-06-01

    Full Text Available Making decision to choose the appropriate target market is one of the key decisions in the success of firms, which has direct effect in the amount of their profits. The aim of this paper is to introduce and use of new hybrid method of AHP, Monte Carlo simulation and PROMETHEE to prioritize cities to establish retailers, considering different indices. The problem of this study is related to a factory, constructing premade pieces of buildings, that to introduce and distribute its new products is searching the new retailers in different cities. To prioritize cities, with the interview with experts and the studying of the previous works the indices have been determined and the hierarchy pattern has been made. Then using the hybrid method of AHP and Monte Carlo simulation the weights of the indices have been determined and then using PROMETHEE method the best city has been chosen and the other ones have been prioritized. From the benefits of the new introduced hybrid method with respect to other ways of selecting target markets is decreasing the risk and increasing the power of decision making.

  17. Generalized window factor analysis for selective analysis of the target component in real samples with complex matrices.

    Science.gov (United States)

    Li, Pao; Cai, Wensheng; Shao, Xueguang

    2015-08-14

    In chromatographic analysis of multicomponent real samples, peak overlapping, high level of noise and background are frequently encountered, making the qualitative and quantitative analysis difficult or even impossible. In this work, an algorithm named as generalized window factor analysis (GWFA) was proposed for quantitative analysis of the target components in the samples with complex matrices by gas chromatography-mass spectrometry (GC-MS). The theory and calculation of GWFA are just similar with the conventional window factor analysis (WFA), but the "window" is defined as the selected channels (mass-to-charge ratios) in the mass spectral dimension of the data matrix, instead of a continuous region in chromatographic dimension along the retention time. Therefore, the generalized window for a target component can be easily determined with the help of the mass spectrum. Then, the calculated mass spectrum can be obtained with the window and quantitative determination can be achieved with the help of the standard. Both simulated and experimental data were investigated with the proposed method. Whether or not a peak shift occurs during the test, accurate results were obtained from the overlapping GC-MS signals with high level of noise and background.

  18. 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.

  19. 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.

  20. Synthetic Cyclolipopeptides Selective against Microbial, Plant and Animal Cell Targets by Incorporation of D-Amino Acids or Histidine.

    Directory of Open Access Journals (Sweden)

    Sílvia Vilà

    Full Text Available 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.

  1. 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.

  2. 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.

  3. Automatic Target Recognition for Hyperspectral Imagery

    Science.gov (United States)

    2012-03-01

    geological exploration, and surveillance (Stein, Beaven, Hoff, Winter, Schaum , & Stocker, 2002). With decreases in manning levels and the ever increasing...another region (Stein, Beaven, Hoff, Winter, Schaum , & Stocker, 2002). “Generally, this [high false-alarm rate] happens due to the well known...Chang, 2004), (Riley, Newsome, & Andrews, 2004), (Kwon & Nasrabadi, 2005), (Gaucel, Guillaume, & Bourennane, 2005), ( Schaum , 2004), (West, Messinger

  4. Enhanced sensitivity for selected reaction monitoring mass spectrometry-based targeted proteomics using a dual stage electrodynamic ion funnel interface.

    Science.gov (United States)

    Hossain, Mahmud; Kaleta, David T; Robinson, Errol W; Liu, Tao; Zhao, Rui; Page, Jason S; Kelly, Ryan T; Moore, Ronald J; Tang, Keqi; Camp, David G; Qian, Wei-Jun; Smith, Richard D

    2011-02-01

    Selected reaction monitoring mass spectrometry (SRM-MS) is playing an increasing role in quantitative proteomics and biomarker discovery studies as a method for high throughput candidate quantification and verification. Although SRM-MS offers advantages in sensitivity and quantification compared with other MS-based techniques, current SRM technologies are still challenged by detection and quantification of low abundance proteins (e.g. present at ∼10 ng/ml or lower levels in blood plasma). Here we report enhanced detection sensitivity and reproducibility for SRM-based targeted proteomics by coupling a nanospray ionization multicapillary inlet/dual electrodynamic ion funnel interface to a commercial triple quadrupole mass spectrometer. Because of the increased efficiency in ion transmission, significant enhancements in overall signal intensities and improved limits of detection were observed with the new interface compared with the original interface for SRM measurements of tryptic peptides from proteins spiked into non-depleted mouse plasma over a range of concentrations. Overall, average SRM peak intensities were increased by ∼70-fold. The average level of detection for peptides also improved by ∼10-fold with notably improved reproducibility of peptide measurements as indicated by the reduced coefficients of variance. The ability to detect proteins ranging from 40 to 80 ng/ml within mouse plasma was demonstrated for all spiked proteins without the application of front-end immunoaffinity depletion and fractionation. This significant improvement in detection sensitivity for low abundance proteins in complex matrices is expected to enhance a broad range of SRM-MS applications including targeted protein and metabolite validation.

  5. Selective targeting of human colon cancer stem-like cells by the mTOR inhibitor Torin-1.

    Science.gov (United States)

    Francipane, Maria Giovanna; Lagasse, Eric

    2013-11-01

    Metastatic colorectal cancer (CRC) is incurable for most patients. Since mammalian target of rapamycin (mTOR) has been suggested as a crucial modulator of tumor biology, we aimed at evaluating the effectiveness of mTOR targeting for CRC therapy. To this purpose, we analyzed mTOR expression and the effect of mTOR inhibition in cancer stem-like cells isolated from three human metastatic CRCs (CoCSCs). CoCSCs exhibited a strong mTOR complex 2 (mTORC2) expression, and a rare expression of mTOR complex 1 (mTORC1). This latter correlated with differentiation, being expressed in CoCSC-derived xenografts. We indicate Serum/glucocorticoid-regulated kinase 1 (SGK1) as the possible main mTORC2 effector in CoCSCs, as highlighted by the negative effect on cancer properties following its knockdown. mTOR inhibitors affected CoCSCs differently, resulting in proliferation, autophagy as well as apoptosis induction. The apoptosis-inducing mTOR inhibitor Torin-1 hindered growth, motility, invasion, and survival of CoCSCs in vitro, and suppressed tumor growth in vivo with a concomitant reduction in vessel formation. Torin-1 also affected the expression of markers for cell proliferation, angio-/lympho-genesis, and stemness in vivo, including Ki67, DLL1, DLL4, Notch, Lgr5, and CD44. Importantly, Torin-1 did not affect the survival of normal colon stem cells in vivo, suggesting its selectivity towards cancer cells. Thus, we propose Torin-1 as a powerful drug candidate for metastatic CRC therapy.

  6. Algal bioremediation of waste waters from land-based aquaculture using ulva: selecting target species and strains.

    Science.gov (United States)

    Lawton, Rebecca J; Mata, Leonardo; de Nys, Rocky; Paul, Nicholas A

    2013-01-01

    The optimised reduction of dissolved nutrient loads in aquaculture effluents through bioremediation requires selection of appropriate algal species and strains. The objective of the current study was to identify target species and strains from the macroalgal genus Ulva for bioremediation of land-based aquaculture facilities in Eastern Australia. We surveyed land-based aquaculture facilities and natural coastal environments across three geographic locations in Eastern Australia to determine which species of Ulva occur naturally in this region and conducted growth trials at three temperature treatments on a subset of samples from each location to determine whether local strains had superior performance under local environmental conditions. DNA barcoding using the markers ITS and tufA identified six species of Ulva, with U. ohnoi being the most common blade species and U. sp. 3 the most common filamentous species. Both species occurred at multiple land-based aquaculture facilities in Townsville and Brisbane and multiple strains of each species grew well in culture. Specific growth rates of U. ohnoi and U. sp. 3 were high (over 9% and 15% day(-1) respectively) across temperature treatments. Within species, strains of U. ohnoi had higher growth in temperatures corresponding to local conditions, suggesting that strains may be locally adapted. However, across all temperature treatments Townsville strains had the highest growth rates (11.2-20.4% day(-1)) and Sydney strains had the lowest growth rates (2.5-8.3% day(-1)). We also found significant differences in growth between strains of U. ohnoi collected from the same geographic location, highlighting the potential to isolate and cultivate fast growing strains. In contrast, there was no clearly identifiable competitive strain of filamentous Ulva, with multiple species and strains having variable performance. The fast growth rates and broad geographical distribution of U. ohnoi make this an ideal species to target for

  7. Histone deacetylase inhibitors selectively target homology dependent DNA repair defective cells and elevate non-homologous endjoining activity.

    Directory of Open Access Journals (Sweden)

    Stephanie Smith

    Full Text Available BACKGROUND: We have previously used the ATAD5-luciferase high-throughput screening assay to identify genotoxic compounds with potential chemotherapeutic capabilities. The successful identification of known genotoxic agents, including the histone deacetylase inhibitor (HDACi trichostatin A (TSA, confirmed the specificity of the screen since TSA has been widely studied for its ability to cause apoptosis in cancer cells. Because many cancers have acquired mutations in DNA damage checkpoints or repair pathways, we hypothesized that these cancers may be susceptible to treatments that target compensatory pathways. Here, we used a panel of isogenic chicken DT40 B lymphocyte mutant and human cell lines to investigate the ability of TSA to define selective pathways that promote HDACi toxicity. RESULTS: HDACi induced a DNA damage response and reduced viability in all repair deficient DT40 mutants although ATM-nulls were least affected. The most dramatic sensitivity was observed in mutants lacking the homology dependent repair (HDR factor BLM or the non-homologous end-joining (NHEJ and HDR factors, KU/RAD54, suggesting an involvement of either HDR or NHEJ in HDACi-induced cell death. To extend these findings, we measured the frequencies of HDR and NHEJ after HDACi treatment and monitored viability in human cell lines comparably deficient in HDR or NHEJ. Although no difference in HDR frequency was observed between HDACi treated and untreated cells, HDR-defective human cell lines were clearly more sensitive than wild type. Unexpectedly, cells treated with HDACis showed a significantly elevated NHEJ frequency. CONCLUSIONS: HDACi targeting drugs induced significant increases in NHEJ activity in human cell lines but did not alter HDR frequency. Moreover, HDR is required for cellular resistance to HDACi therapy; therefore, NHEJ does not appear to be a critical axis for HDACi resistance. Rather, HDACi compounds induced DNA damage, most likely double strand breaks

  8. Targeting of liver tumour in rats by selective delivery of holmium-166 loaded microspheres: a biodistribution study

    Energy Technology Data Exchange (ETDEWEB)

    Nijsen, F.; Rook, D.; Zonnenberg, B.; Klerk, J. de; Rijk, P. van; Schip, F. van het [Dept. of Nuclear Medicine, University Medical Center, Utrecht (Netherlands); Brandt, C. [Animal Inst., Utrecht Univ. (Netherlands); Meijer, R. [Dept. of Radiology, Univ. Medical Center, Utrecht (Netherlands); Dullens, H. [Dept. of Pathology, Univ. Medical Center, Utrecht (Netherlands); Hennink, W. [Dept. of Pharmaceutics, Utrecht Univ. (Netherlands)

    2001-06-01

    Intra-arterial administration of beta-emitting particles that become trapped in the vascular bed of a tumour and remain there while delivering high doses, represents a unique approach in the treatment of both primary and metastatic liver tumours. Studies on selective internal radiation therapy of colorectal liver metastases using yttrium-90 glass microspheres have shown encouraging results. This study describes the biodistribution of 40-{mu}m poly lactic acid microspheres loaded with radioactive holmium-166, after intra-arterial administration into the hepatic artery of rats with implanted liver tumours. Radioactivity measurements showed >95% retention of injected activity in the liver and its resident tumour. The average activity detected in other tissues was {<=}0.1%ID/g, with incidental exceptions in the lungs and stomach. Very little {sup 166}Ho activity was detected in kidneys (<0.1%ID/g), thereby indicating the stability of the microspheres in vivo. Tumour targeting was very effective, with a mean tumour to liver ratio of 6.1{+-}2.9 for rats with tumour (n=15) versus 0.7{+-}0.5 for control rats (n=6; P<0.001). These ratios were not significantly affected by the use of adrenaline. Histological analysis showed that five times as many large (>10) and medium-sized (4-9) clusters of microspheres were present within tumour and peritumoural tissue, compared with normal liver. Single microspheres were equally dispersed throughout the tumour, as well as normal liver parenchyma. (orig.)

  9. Comparison of targeted peptide quantification assays for reductive dehalogenases by selective reaction monitoring (SRM) and precursor reaction monitoring (PRM).

    Science.gov (United States)

    Schiffmann, Christian; Hansen, Rasmus; Baumann, Sven; Kublik, Anja; Nielsen, Per Halkjær; Adrian, Lorenz; von Bergen, Martin; Jehmlich, Nico; Seifert, Jana

    2014-01-01

    Targeted absolute protein quantification yields valuable information about physiological adaptation of organisms and is thereby of high interest. Especially for this purpose, two proteomic mass spectrometry-based techniques namely selective reaction monitoring (SRM) and precursor reaction monitoring (PRM) are commonly applied. The objective of this study was to establish an optimal quantification assay for proteins with the focus on those involved in housekeeping functions and putative reductive dehalogenase proteins from the strictly anaerobic bacterium Dehalococcoides mccartyi strain CBDB1. This microbe is small and slow-growing; hence, it provides little biomass for comprehensive proteomic analysis. We therefore compared SRM and PRM techniques. Eleven peptides were successfully quantified by both methods. In addition, six peptides were solely quantified by SRM and four by PRM, respectively. Peptides were spiked into a background of Escherichia coli lysate and the majority of peptides were quantifiable down to 500 amol absolute on column by both methods. Peptide quantification in CBDB1 lysate resulted in the detection of 15 peptides using SRM and 14 peptides with the PRM assay. Resulting quantification of five dehalogenases revealed copy numbers of <10 to 115 protein molecules per cell indicating clear differences in abundance of RdhA proteins during growth on hexachlorobenzene. Our results indicated that both methods show comparable sensitivity and that the combination of the mass spectrometry assays resulted in higher peptide coverage and thus more reliable protein quantification.

  10. Metal concentrations in selected brands of canned fish in Nigeria: estimation of dietary intakes and target hazard quotients.

    Science.gov (United States)

    Iwegbue, Chukwujindu M A

    2015-03-01

    The concentrations of metals (Cd, Pb, Ni, Cr, Cu, Co, Fe, Mn, and Zn) were determined in selected brands of canned mackerel, sardine, and tuna in Nigeria with a view to providing information on the dietary intakes of metals and lifelong health hazards associated with the consumption of these products. The concentrations of metals were determined by using atomic absorption spectrometry after acid digestion. The mean concentrations of metals in canned mackerel, sardine, and tuna were found as 0.04-0.58, 0.06-0.44, 0.32-0.83 μg/g for Cd; 0.05-2.82, 0.70-2.98, 0.23-2.56 μg/g for Pb, 1.33-11.33, canned fish were above their permissible limits while other metals occurred at levels below their permissible limits. The estimated daily intakes of metals from consumption of 20.8 g fish per day by a 60 kg body weight adult were below the provisional tolerable daily intakes for Cd, Pb, Ni, Cr, and Cu and recommended daily intakes for Co, Fe, Mn, and Zn. The estimated target hazard quotients of the examined metals were less than 1 in the majority of the samples indicating no long-term health hazard at the present circumstance.

  11. 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.

  12. 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.

  13. An Earthquake Ground Motion Database System with Automatic Record Selection Methods%一种支持自动化选波的地震波数据库系统

    Institute of Scientific and Technical Information of China (English)

    徐亚军; 王朝坤; 魏冬梅; 施炜; 潘鹏

    2011-01-01

    With many earthquakes happening in recent years, the seismic performance of building structures is more and more important. How to select earthquake ground motion records for testing buildings is becoming much more necessary. Although the Occident has set up some earthquake ground motion database systems for researches of seismic performance of building structures, these database systems are not able to cover characteristics of earthquake ground motions of our country, nor offer record election methods meeting requirements of our engineering designs, let alone the automatic record selection method. Therefore, it is much necessary to develop an earthquake ground motion database system and scientific and reasonable selection methods of our country immediately. This paper presents an earthquake ground motion database system, which collects a lot of earthquake ground motion records. And the system supports two kinds of earthquake ground motion record selection methods: the conditional ground motion selection method and the severest ground motion selection method. Many experiments prove that the efficiency and effects of earthquake ground motion record selection methods can both meet users' requirements.%近年来地震频发,建筑结构的抗震性越来越被人们所重视,因此如何选取需要的地震波来检测建筑结构变得非常重要.虽然欧美等国家已经建立了一些用于结构抗震研究的地震波数据库系统,但是这些数据库系统均未能涵盖能反映我国地震动特征的地震波,也未能提供满足我国工程设计的选波方法,更没有实现自动化选波,所以迅速开发我国自己的地震波数据库系统和研究科学合理的选波方法显得十分必要.设计并实现了一种可以自动化选波的地震波数据库系统,该系统收集了许多具有代表性和权威性的地震波,并支持条件选波和最不利选波.大量的实验表明,该地震波数据库系统的选波效率、选波

  14. 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.

  15. 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.

  16. 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.

  17. Activated platelets in carotid artery thrombosis in mice can be selectively targeted with a radiolabeled single-chain antibody.

    Directory of Open Access Journals (Sweden)

    Timo Heidt

    Full Text Available BACKGROUND: Activated platelets can be found on the surface of inflamed, rupture-prone and ruptured plaques as well as in intravascular thrombosis. They are key players in thrombosis and atherosclerosis. In this study we describe the construction of a radiolabeled single-chain antibody targeting the LIBS-epitope of activated platelets to selectively depict platelet activation and wall-adherent non-occlusive thrombosis in a mouse model with nuclear imaging using in vitro and ex vivo autoradiography as well as small animal SPECT-CT for in vivo analysis. METHODOLOGY/PRINCIPAL FINDINGS: LIBS as well as an unspecific control single-chain antibody were labeled with (111Indium ((111In via bifunctional DTPA ( = (111In-LIBS/(111In-control. Autoradiography after incubation with (111In-LIBS on activated platelets in vitro (mean 3866 ± 28 DLU/mm(2, 4010 ± 630 DLU/mm(2 and 4520 ± 293 DLU/mm(2 produced a significantly higher ligand uptake compared to (111In-control (2101 ± 76 DLU/mm(2, 1181 ± 96 DLU/mm(2 and 1866 ± 246 DLU/mm(2 indicating a specific binding to activated platelets; P<0.05. Applying these findings to an ex vivo mouse model of carotid artery thrombosis revealed a significant increase in ligand uptake after injection of (111In-LIBS in the presence of small thrombi compared to the non-injured side, as confirmed by histology (49630 ± 10650 DLU/mm(2 vs. 17390 ± 7470 DLU/mm(2; P<0.05. These findings could also be reproduced in vivo. SPECT-CT analysis of the injured carotid artery with (111In-LIBS resulted in a significant increase of the target-to-background ratio compared to (111In-control (1.99 ± 0.36 vs. 1.1 ± 0.24; P < 0.01. CONCLUSIONS/SIGNIFICANCE: Nuclear imaging with (111In-LIBS allows the detection of platelet activation in vitro and ex vivo with high sensitivity. Using SPECT-CT, wall-adherent activated platelets in carotid arteries could be depicted in vivo. These results encourage further studies elucidating the role of

  18. 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.

  19. 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

  20. 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

  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. Mediation and Automatization.

    Science.gov (United States)

    Hutchins, Edwin

    This paper discusses the relationship between the mediation of task performance by some structure that is not inherent in the task domain itself and the phenomenon of automatization, in which skilled performance becomes effortless or phenomenologically "automatic" after extensive practice. The use of a common simple explicit mediating…

  3. Digital automatic gain control

    Science.gov (United States)

    Uzdy, Z.

    1980-01-01

    Performance analysis, used to evaluated fitness of several circuits to digital automatic gain control (AGC), indicates that digital integrator employing coherent amplitude detector (CAD) is best device suited for application. Circuit reduces gain error to half that of conventional analog AGC while making it possible to automatically modify response of receiver to match incoming signal conditions.

  4. Automatic Differentiation Package

    Energy Technology Data Exchange (ETDEWEB)

    2007-03-01

    Sacado is an automatic differentiation package for C++ codes using operator overloading and C++ templating. Sacado provide forward, reverse, and Taylor polynomial automatic differentiation classes and utilities for incorporating these classes into C++ codes. Users can compute derivatives of computations arising in engineering and scientific applications, including nonlinear equation solving, time integration, sensitivity analysis, stability analysis, optimization and uncertainity quantification.

  5. Automatic aircraft recognition

    Science.gov (United States)

    Hmam, Hatem; Kim, Jijoong

    2002-08-01

    Automatic aircraft recognition is very complex because of clutter, shadows, clouds, self-occlusion and degraded imaging conditions. This paper presents an aircraft recognition system, which assumes from the start that the image is possibly degraded, and implements a number of strategies to overcome edge fragmentation and distortion. The current vision system employs a bottom up approach, where recognition begins by locating image primitives (e.g., lines and corners), which are then combined in an incremental fashion into larger sets of line groupings using knowledge about aircraft, as viewed from a generic viewpoint. Knowledge about aircraft is represented in the form of whole/part shape description and the connectedness property, and is embedded in production rules, which primarily aim at finding instances of the aircraft parts in the image and checking the connectedness property between the parts. Once a match is found, a confidence score is assigned and as evidence in support of an aircraft interpretation is accumulated, the score is increased proportionally. Finally a selection of the resulting image interpretations with the highest scores, is subjected to competition tests, and only non-ambiguous interpretations are allowed to survive. Experimental results demonstrating the effectiveness of the current recognition system are given.

  6. The effect of spatial organization of targets and distractors on the capacity to selectively memorize objects in visual short-term memory.

    Science.gov (United States)

    Abbes, Aymen Ben; Gavault, Emmanuelle; Ripoll, Thierry

    2014-01-01

    We conducted a series of experiments to explore how the spatial configuration of objects influences the selection and the processing of these objects in a visual short-term memory task. We designed a new experiment in which participants had to memorize 4 targets presented among 4 distractors. Targets were cued during the presentation of distractor objects. Their locations varied according to 4 spatial configurations. From the first to the last configuration, the distance between targets' locations was progressively increased. The results revealed a high capacity to select and memorize targets embedded among distractors even when targets were extremely distant from each other. This capacity is discussed in relation to the unitary conception of attention, models of split attention, and the competitive interaction model. Finally, we propose that the spatial dispersion of objects has different effects on attentional allocation and processing stages. Thus, when targets are extremely distant from each other, attentional allocation becomes more difficult while processing becomes easier. This finding implicates that these 2 aspects of attention need to be more clearly distinguished in future research.

  7. Symmetrical Key Automatic Changing Cryptography Based on Simple Hybrid Selection Coding%基于简易混合选择编码的对称密钥自变动加密

    Institute of Scientific and Technical Information of China (English)

    罗俊; 张国平

    2012-01-01

    Aiming at the encryption system with lower security requirements, this paper puts forward a symmetrical key automatic changing cryptography scheme based on simple hybrid selection coding, with the combination of unilateral canonical Huffman coding and fixed-length coding. The statistical results of plaintext are used as their own encrypted key and coding basis, which makes the scheme to be easy to implement and calculate and of cost low. It is proved that when the keys are completely unknown, the cracking of the encryption system has great difficulty.%针对安全性要求不太高的加密系统,将单边范式Huffman编码与等长编码相结合,提出一种基于混合选择编码的对称密钥自变动加密方案.通过将明文的统计结果作为自身加密的密钥和编码依据,使方案易于实现,且计算存储成本低.理论分析结果证明,在密钥完全未知的情况下破解该加密体制难度较大.

  8. 基于自适应特征选择的自动白平衡方法%Automatic White Balance Method Based on Self-adaptive Feature Selection

    Institute of Scientific and Technical Information of China (English)

    印蔚蔚

    2015-01-01

    This paper presents a method of automatic white balance based on self adaptive feature selection. Three kinds of neutral color feature is used in the process: the characteristics of the modified grey world, white spot method of linear fea-ture and color clustering, they are complementary to each other and the calculation of the effectiveness. the test results show that the proposed algorithm is superior to the traditional and in a wide range of scenarios to color compensation and reason-able.%文章提出了一种基于自适应特征选择的自动白平衡方法。该方法中使用了3种中性颜色特征:修改过的灰色世界法的特征、白斑法的特征以及线性颜色聚类的特征,它们具有互补性和计算有效性。试验结果证明文章提出的算法优于传统的以假设为基础的方法并且在广泛的场景上达到了合理的色彩补偿。

  9. 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.

  10. A novel 9 × 9 map-based solvent selection strategy for targeted counter-current chromatography isolation of natural products.

    Science.gov (United States)

    Liang, Junling; Meng, Jie; Wu, Dingfang; Guo, Mengzhe; Wu, Shihua

    2015-06-26

    Counter-current chromatography (CCC) is an efficient liquid-liquid chromatography technique for separation and purification of complex mixtures like natural products extracts and synthetic chemicals. However, CCC is still a challenging process requiring some special technical knowledge especially in the selection of appropriated solvent systems. In this work, we introduced a new 9 × 9 map-based solvent selection strategy for CCC isolation of targets, which permit more than 60 hexane-ethyl acetate-methanol-water (HEMWat) solvent systems as the start candidates for the selection of solvent systems. Among these solvent systems, there are clear linear correlations between partition coefficient (K) and the system numbers. Thus, an appropriate CCC solvent system (i.e., sweet spot for K = 1) may be hit by measurement of k values of the target only in two random solvent systems. Besides this, surprisingly, we found that through two sweet spots, we could get a line ("Sweet line") where there are infinite sweet solvent systems being suitable for CCC separation. In these sweet solvent systems, the target has the same partition coefficient (K) but different solubilities. Thus, the better sweet solvent system with higher sample solubility can be obtained for high capacity CCC preparation. Furthermore, we found that there is a zone ("Sweet zone") where all solvent systems have their own sweet partition coefficients values for the target in range of 0.4 natural products as standards and further confirmed by isolation of several targets including honokiol and magnolol from the extracts of Magnolia officinalis Rehd. Et Wils and tanshinone IIA from Salvia miltiorrhiza Bunge. In practice, it is much easier to get a suitable solvent system only by making a simple screening two to four HEMWat two-phase solvent systems to obtain the sweet line or sweet zone without special knowledge or comprehensive standards as references. This is an important advancement for solvent system selection

  11. Band Selection for Aircraft Targets Detection%面向飞机目标探测的波段选择方法

    Institute of Scientific and Technical Information of China (English)

    祁鸣; 刘德连; 张二磊

    2011-01-01

    针对飞机目标的探测与抗干扰问题,提出一种新的面向飞机目标探测的波段选择方法,通过耦合分析飞机目标、背景、大气、成像系统和干扰的特性,建立目标和背景的信噪比模型,确定出探测波段的中心.在此基础上,不断扩展探测波段,并分析信噪比的变化,得到探测波段的宽度.随后,根据干扰目标的辐射特性,添加抗干扰波段,有效解决了目标探测和抗干扰的结合.将所选择的探测波段应用于飞机目标的探测,仿真结果表明我们给出的波段选择方法得到的探测波段能够提高系统探测距离,同时具有一定的抗干扰能力.%To improve the performance of detection and anti-jamming of aircraft targets, a new band selection method is proposed. Base on the coupling analysis of the characteristics of aircraft targets, background, atmosphere, detection systems, and infrared-decoy, a signal to noise model (SNR) is build. And the center of the selected band is determined. Next, the width of the selected band is enlarged step by step to show the change of the SNR. As the SNR grows slowly and flatly, the width of the selected band is the final selected band. Subsequently, the characteristics of infrared-decoy are also analyzed. And a supplement band is got for anti-jamming. We test the band selection method by applying our selected bands to aircraft targets detection. The results indicate that the selected bands obtained by our new band selection method can improve the detection performance of aircraft targets and have good ability for Anti-jamming.

  12. Automatic Selection of Classified Samples with the Help of Previous Land Cover Data%前期土地覆被数据辅助下的分类样本自动选取

    Institute of Scientific and Technical Information of China (English)

    刘锟; 杨晓梅; 张涛

    2012-01-01

    The combination of geographical knowledge and image calibration has long been the principal means of both the traditional visual interpretation and computer automatic classification in remote sensing mapping. Traditional visual interpretation could use the geographic knowledge well because of the artificial participation. However, it goes with the shortcomings that visual interpretation needs a lot of labor and is less efficient. In addition, the computer classification has not applied geographic knowledge in a proper way. Studies have shown that samples as the carrier of geographic knowledge can integrate geographic knowledge into the classification process to some extent. Meanwhile, unsupervised clustering can significantly improve the efficiency of sample selection and solve the problem of scarcity of samples in order to meet the requirement of distribution and purity. These studies provide a basic foundation for integration of geographic knowledge with computer classification. This paper presents an automatic sample selecting method which integrates image clustering with the and of previous land cover data. The samples were selected automatically based on the TM images by the method mentioned above and used to classify the image later by the maximum likelihood classifier. We also classified the image using the manual samples by the maximum likelihood classifier in order to compare the classified results produced by these two kinds of samples. The test results indicated that the proposed method achieved an overail accuracy of 84. 18% and a kappa coefficient of 0. 8066 in seven categories, including water body, forest land, orchard and urban construction land. The method proposed in this paper is more efficient than the way of samples selected manually and provides better classification results.%将地学知识与影像标定相结合,一直是目视解译或计算机自动分类制图的主要手段.传统的目视解译方法能够充分利用地学知识,但

  13. Word Automaticity of Tree Automatic Scattered Linear Orderings Is Decidable

    CERN Document Server

    Huschenbett, Martin

    2012-01-01

    A tree automatic structure is a structure whose domain can be encoded by a regular tree language such that each relation is recognisable by a finite automaton processing tuples of trees synchronously. Words can be regarded as specific simple trees and a structure is word automatic if it is encodable using only these trees. The question naturally arises whether a given tree automatic structure is already word automatic. We prove that this problem is decidable for tree automatic scattered linear orderings. Moreover, we show that in case of a positive answer a word automatic presentation is computable from the tree automatic presentation.

  14. Automatic TLI recognition system, general description

    Energy Technology Data Exchange (ETDEWEB)

    Lassahn, G.D.

    1997-02-01

    This report is a general description of an automatic target recognition system developed at the Idaho National Engineering Laboratory for the Department of Energy. A user`s manual is a separate volume, Automatic TLI Recognition System, User`s Guide, and a programmer`s manual is Automatic TLI Recognition System, Programmer`s Guide. This system was designed as an automatic target recognition system for fast screening of large amounts of multi-sensor image data, based on low-cost parallel processors. This system naturally incorporates image data fusion, and it gives uncertainty estimates. It is relatively low cost, compact, and transportable. The software is easily enhanced to expand the system`s capabilities, and the hardware is easily expandable to increase the system`s speed. In addition to its primary function as a trainable target recognition system, this is also a versatile, general-purpose tool for image manipulation and analysis, which can be either keyboard-driven or script-driven. This report includes descriptions of three variants of the computer hardware, a description of the mathematical basis if the training process, and a description with examples of the system capabilities.

  15. Potential tumor-tropic effect of genetically engineered stem cells expressing suicide enzymes to selectively target invasive cancer in animal models.

    Science.gov (United States)

    Kim, Seung U; Jeung, Eui-Bae; Kim, Yun-Bae; Cho, Myung-Haing; Choi, Kyung-Chul

    2011-04-01

    Stem cells have recently received a great deal of attention for their clinical and therapeutic potential to treat human disease and disorders. For instance, neural stem cells expressing a suicide gene which can concert prodrugs to their active metabolites may have great tropic and therapeutic potential for brain tumors, i.e., medulloblastoma and glioma. We are currently interested in therapeutic potential of these genetically engineered stem cells (GESTECs) to selectively target invasive tumors, i.e. ovarian, endometrial, breast, and lung cancer which can have a great impact on human and animal health. Thus, in this review we summarize the therapeutic potential of GESTEC, developed by us, and the putative mechanism(s) underlying their therapeutic and tropic potential in expressing suicide genes which can convert prodrugs to their active metabolites and in selectively targeting invasive tumors.

  16. Short tandem target mimic: a long journey to the engineered molecular landmine for selective destruction/blockage of microRNAs in plants and animals.

    Science.gov (United States)

    Tang, Guiliang; Tang, Xiaoqing

    2013-06-20

    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.

  17. 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.

  18. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.

    Directory of Open Access Journals (Sweden)

    Rosario Diaz

    2014-10-01

    Full Text Available In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2 cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053. This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.

  19. Identification and characterization of hundreds of potent and selective inhibitors of Trypanosoma brucei growth from a kinase-targeted library screening campaign.

    Science.gov (United States)

    Diaz, Rosario; Luengo-Arratta, Sandra A; Seixas, João D; Amata, Emanuele; Devine, William; Cordon-Obras, Carlos; Rojas-Barros, Domingo I; Jimenez, Elena; Ortega, Fatima; Crouch, Sabrinia; Colmenarejo, Gonzalo; Fiandor, Jose Maria; Martin, Jose Julio; Berlanga, Manuela; Gonzalez, Silvia; Manzano, Pilar; Navarro, Miguel; Pollastri, Michael P

    2014-10-01

    In the interest of identification of new kinase-targeting chemotypes for target and pathway analysis and drug discovery in Trypanosomal brucei, a high-throughput screen of 42,444 focused inhibitors from the GlaxoSmithKline screening collection was performed against parasite cell cultures and counter-screened against human hepatocarcinoma (HepG2) cells. In this way, we have identified 797 sub-micromolar inhibitors of T. brucei growth that are at least 100-fold selective over HepG2 cells. Importantly, 242 of these hit compounds acted rapidly in inhibiting cellular growth, 137 showed rapid cidality. A variety of in silico and in vitro physicochemical and drug metabolism properties were assessed, and human kinase selectivity data were obtained, and, based on these data, we prioritized three compounds for pharmacokinetic assessment and demonstrated parasitological cure of a murine bloodstream infection of T. brucei rhodesiense with one of these compounds (NEU-1053). This work represents a successful implementation of a unique industrial-academic collaboration model aimed at identification of high quality inhibitors that will provide the parasitology community with chemical matter that can be utilized to develop kinase-targeting tool compounds. Furthermore these results are expected to provide rich starting points for discovery of kinase-targeting tool compounds for T. brucei, and new HAT therapeutics discovery programs.

  20. Neuropeptide Y Y1 receptors meditate targeted delivery of anticancer drug with encapsulated nanoparticles to breast cancer cells with high selectivity and its potential for breast cancer therapy.

    Science.gov (United States)

    Li, Juan; Shen, Zheyu; Ma, Xuehua; Ren, Wenzhi; Xiang, Lingchao; Gong, An; Xia, Tian; Guo, Junming; Wu, Aiguo

    2015-03-11

    By enabling nanoparticle-based drug delivery system to actively target cancer cells with high selectivity, active targeted molecules have attracted great attention in the application of nanoparticles for anticancer drug delivery. However, the clinical application of most active targeted molecules in breast cancer therapy is limited, due to the low expression of their receptors in breast tumors or coexpression in the normal and tumor breast tissues. Here, a neuropeptide Y Y1 receptors ligand PNBL-NPY, as a novel targeted molecule, is conjugated with anticancer drug doxorubicin encapsulating albumin nanoparticles to investigate the effect of Y1 receptors on the delivery of drug-loaded nanoparticles to breast cancer cells and its potential for breast cancer therapy. The PNBL-NPY can actively recognize and bind to the Y1 receptors that are significantly overexpressed on the surface of the breast cancer cells, and the drug-loaded nanoparticles are delivered directly into the cancer cells through internalization. This system is highly selective and able to distinguish the breast cancer cells from the normal cells, due to normal breast cells that express Y2 receptors only. It is anticipated that this study may provide a guidance in the development of Y1 receptor-based nanoparticulate drug delivery system for a safer and more efficient breast cancer therapy.

  1. Transit peptide elements mediate selective protein targeting to two different types of chloroplasts in the single-cell C4 species Bienertia sinuspersici

    Science.gov (United States)

    Wimmer, Diana; Bohnhorst, Philipp; Shekhar, Vinay; Hwang, Inhwan; Offermann, Sascha

    2017-01-01

    Bienertia sinuspersici is a terrestrial plant that performs C4 photosynthesis within individual cells through operating a carbon concentrating mechanism between different subcellular domains including two types of chloroplasts. It is currently unknown how differentiation of two highly specialized chloroplasts within the same cell occurs as no similar cases have been reported. Here we show that this differentiation in photosynthetic cells of B. sinuspersici is enabled by a transit peptide (TP) mediated selective protein targeting mechanism. Mutations in the TPs cause loss of selectivity but not general loss of chloroplast import, indicating the mechanism operates by specifically blocking protein accumulation in one chloroplast type. Hybrid studies indicate that this selectivity is transferable to transit peptides of plants which perform C4 by cooperative function of chloroplasts between two photosynthetic cells. Codon swap experiments as well as introducing an artificial bait mRNA show that RNA affects are not crucial for the sorting process. In summary, our analysis shows how the mechanism of subcellular targeting to form two types of chloroplast within the same cell can be achieved. This information is not only crucial for understanding single-cell C4 photosynthesis; it provides new insights in control of subcellular protein targeting in cell biology. PMID:28112241

  2. 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...

  3. 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.

  4. Stable expression of green fluorescent protein and targeted disruption of thioredoxin peroxidase-1 gene in Babesia bovis with the WR99210/dhfr selection system.

    Science.gov (United States)

    Asada, Masahito; Tanaka, Miho; Goto, Yasuyuki; Yokoyama, Naoaki; Inoue, Noboru; Kawazu, Shin-ichiro

    2012-02-01

    We have achieved stable expression of green fluorescent protein (GFP) in Babesia bovis by using the WR99210/human dihydrofolate reductase (DHFR) gene selection system. A GFP-expression plasmid with a dhfr expression cassette (DHFR-gfp) was constructed and transfected into B. bovis by nucleofection. Following WR99210 selection, a GFP-fluorescent parasite population was obtained and the fluorescent parasite was maintained for more than 7 months under WR99210 drug pressure. The DHFR-gfp was used to construct a small circular chromosome and to target gene disruption in the parasite. For construction of the small circular chromosome (DHFR-gfp-Bbcent2), the putative centromere region of B. bovis chromosome 2 (Bbcent2) was cloned and inserted into the DHFR-gfp plasmid. Addition of Bbcent2 to the DHFR-gfp plasmid improved its segregation efficiency during parasite multiplication and GFP-expressing parasites were maintained for more than 2 months without drug pressure. For targeted disruption of a B. bovis gene we attempted to knockout the thioredoxin peroxidase-1 (TPx-1) gene (a single-copy 2-Cys peroxiredoxin gene, Tbtpx-1) by homologous recombination. To generate the targeting construct (DHFR-gfp-Bbtpx1KO), 5' and 3' portions of Bbtpx-1 were cloned into the DHFR-gfp plasmid. Following nucleofection, WR99210 selection and cloning, a GFP-fluorescent parasite population was obtained. Integration of the construct into the Bbtpx-1 locus was confirmed by PCR. The absence of Bbtpx-1 mRNA and protein were verified by reverse transcription PCR and western blot analysis/indirect immunofluorescence assay, respectively. This is the first report of targeted gene disruption of a Babesia gene. These advances in the methodology of genetic manipulation in B. bovis will facilitate functional analysis of Babesia genomes and will improve our understanding of the basic biology of apicomplexan parasites.

  5. 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.

  6. Automatic Program Development

    DEFF Research Database (Denmark)

    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......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...

  7. Latest results on searches for dark matter signatures in galactic and extragalactic selected targets by the MAGIC Telescopes

    Science.gov (United States)

    Giammaria, P.; Aleksić, J.; Lombardi, S.; Maggio, C.; Palacio, J.; Rico, J.; Vanzo, G.; Vazquez Acosta, M.; MAGIC Collaboration

    2016-05-01

    Discovering the nature of Dark Matter (DM) is one of the fundamental challenges of the modern physics. Indirect searches of DM are devoted to look for non-gravitational signals of its presence in the highly DM dominated cosmic regions. Within the weakly interacting massive particles (WIMPs) scenario, we expect very high energy (VHE) gamma-ray emissions resulting from annihilation and/or decay of DM particles. Since the beginning of operations, the Major Atmospheric Gamma Imaging Cherenkov (MAGIC) telescopes are carrying out deep observations of several promising DM targets, with the aim of detecting such signals or alternatively setting stringent constrains to DM particle models in the TeV mass region. In this contribution we present the latest indirect DM search results achieved by MAGIC on several targets, such as dwarf satellites - where MAGIC reached the strongest constraints on DM annihilation searches above few hundreds of GeV -, galaxy clusters, and the Galactic Center.

  8. Automatization and training in visual search.

    Science.gov (United States)

    Czerwinski, M; Lightfoot, N; Shiffrin, R M

    1992-01-01

    In several search tasks, the amount of practice on particular combinations of targets and distractors was equated in varied-mapping (VM) and consistent-mapping (CM) conditions. The results indicate the importance of distinguishing between memory and visual search tasks, and implicate a number of factors that play important roles in visual search and its learning. Visual search was studied in Experiment 1. VM and CM performance were almost equal, and slope reductions occurred during practice for both, suggesting the learning of efficient attentive search based on features, and no important role for automatic attention attraction. However, positive transfer effects occurred when previous CM targets were re-paired with previous CM distractors, even though these targets and distractors had not been trained together. Also, the introduction of a demanding simultaneous task produced advantages of CM over VM. These latter two results demonstrated the operation of automatic attention attraction. Visual search was further studied in Experiment 2, using novel characters for which feature overlap and similarity were controlled. The design and many of the findings paralleled Experiment 1. In addition, enormous search improvement was seen over 35 sessions of training, suggesting the operation of perceptual unitization for the novel characters. Experiment 3 showed a large, persistent advantage for CM over VM performance in memory search, even when practice on particular combinations of targets and distractors was equated in the two training conditions. A multifactor theory of automatization and attention is put forth to account for these findings and others in the literature.

  9. Rehashing endocannabinoid antagonists: can we selectively target the periphery to safely treat obesity and type 2 diabetes?

    OpenAIRE

    Patti, Mary-Elizabeth

    2010-01-01

    A growing body of evidence supports an important role for the endocannabinoid system as a regulator of appetite, body weight, and systemic metabolism, which is overactive in obesity and type 2 diabetes. While initial attempts to target this system using the cannabinoid receptor inverse agonist rimonabant were successful in producing modest weight loss and improving obesity-related metabolic complications in humans, adverse central nervous system side effects precluded introduction of this dru...

  10. 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

  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. Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesis

    NARCIS (Netherlands)

    Smits, Bart M G; Mudde, Josine B; van de Belt, Jose; Verheul, Mark; Olivier, Jocelien; Homberg, Judith; Guryev, Victor; Cools, Alexander R; Ellenbroek, Bart A; Plasterk, Ronald H A; Cuppen, Edwin

    2006-01-01

    OBJECTIVE: The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits using existing rat strains, thereby solely depending o

  13. Generation of gene knockouts and mutant models in the laboratory rat by ENU-driven target-selected mutagenesis.

    NARCIS (Netherlands)

    Smits, B.M.; Mudde, J.B.; Belt, J. van de; Verheul, M.; Olivier, J.; Homberg, J.R.; Guryev, V.; Cools, A.R.; Ellenbroek, B.A.; Plasterk, R.H.; Cuppen, E.

    2006-01-01

    OBJECTIVE: The rat is one of the most important model organisms for biomedical and pharmacological research. However, the generation of novel models for studying specific aspects of human diseases largely depends on selection for specific traits using existing rat strains, thereby solely depending o

  14. Phylogenetic selection of target species in Amaryllidaceae tribe Haemantheae for acetylcholinesterase inhibition and affinity to the serotonin reuptake transport protein

    Science.gov (United States)

    We present phylogenetic analyses of 37 taxa of Amaryllidaceae, tribe Haemantheae and Amaryllis belladonna L. as an outgroup, in order to provide a phylogenetic framework for the selection of candidate plants for lead discoveries in relation to Alzheimer´s disease and depression. DNA sequences from t...

  15. 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.

  16. 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.

  17. Surrogate species selection for assessing potential adverse environmental impacts of genetically engineered insect-resistant plants on non-target organisms.

    Science.gov (United States)

    Carstens, Keri; Cayabyab, Bonifacio; De Schrijver, Adinda; Gadaleta, Patricia G; Hellmich, Richard L; Romeis, Jörg; Storer, Nicholas; Valicente, Fernando H; Wach, Michael

    2014-01-01

    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 are assessed using surrogate species, and it is critical that the data derived from surrogates accurately predict any adverse impacts likely to be observed from the use of the crop in the agricultural context. The key is to select surrogate species that best represent the valued NTOs in the location where the crop is going to be introduced, but this selection process poses numerous challenges for the developers of GE crops who will perform the tests, as well as for the ecologists and regulators who will interpret the test results. These issues were the subject of a conference "Surrogate Species Selection for Assessing Potential Adverse Environmental Impacts of Genetically Engineered Plants on Non-Target Organisms" convened by the Center for Environmental Risk Assessment, ILSI Research Foundation. This report summarizes the proceedings of the conference, including the presentations, discussions and the points of consensus agreed to by the participants.

  18. Design, synthesis, and biological evaluation of folic acid targeted tetraphenylporphyrin as novel photosensitizers for selective photodynamic therapy.

    Science.gov (United States)

    Schneider, Raphaël; Schmitt, Frédéric; Frochot, Céline; Fort, Yves; Lourette, Natacha; Guillemin, François; Müller, Jean-François; Barberi-Heyob, Muriel

    2005-04-15

    Photodynamic therapy (PDT) is a cancer treatment involving systemic administration of a tumor-localizing photosensitizer; this, when activated by the appropriate light wavelength, interacts with molecular oxygen to form a toxic, short-lived species known as singlet oxygen, which is thought to mediate cellular death. Targeted PDT offers the opportunity of enhancing photodynamic efficiency by directly targeting diseased cells and tissues. Two new conjugates of three components, folic acid/hexane-1,6-diamine/4-carboxyphenylporphyrine 1 and folic acid/2,2'-(ethylenedioxy)-bis-ethylamine/4-carboxyphenylporphyrine 2 were synthesized. The conjugates were characterized by 1H NMR, MALDI, UV-visible spectroscopy, and fluorescence quantum yield. The targeted delivery of these photoactive compounds to KB nasopharyngeal cell line, which is one of the numerous tumor cell types that overexpress folate receptors was studied. It was found that after 24 h incubation, conjugates 1 and 2 cellular uptake was on average 7-fold higher than tetraphenylporphyrin (TPP) used as reference and that 1 and 2 cellular uptake kinetics increased steadily over the 24 h period, suggesting an active transport via receptor-mediated endocytosis. In corresponding results, conjugates 1 and 2 accumulation displayed a reduction of 70% in the presence of a competitive concentration of folic acid. Survival measurements demonstrated that KB cells were significantly more sensitive to conjugated porphyrins-mediated PDT. Under the same experimental conditions and the same photosensitizer concentration, TPP displayed no photocytotoxicity while conjugates 1 and 2 showed photodynamic activity with light dose values yielding 50% growth inhibition of 22.6 and 6.7 J/cm2, respectively.

  19. Automatic Fastening Large Structures: a New Approach

    Science.gov (United States)

    Lumley, D. F.

    1985-01-01

    The external tank (ET) intertank structure for the space shuttle, a 27.5 ft diameter 22.5 ft long externally stiffened mechanically fastened skin-stringer-frame structure, was a labor intensitive manual structure built on a modified Saturn tooling position. A new approach was developed based on half-section subassemblies. The heart of this manufacturing approach will be 33 ft high vertical automatic riveting system with a 28 ft rotary positioner coming on-line in mid 1985. The Automatic Riveting System incorporates many of the latest automatic riveting technologies. Key features include: vertical columns with two sets of independently operating CNC drill-riveting heads; capability of drill, insert and upset any one piece fastener up to 3/8 inch diameter including slugs without displacing the workpiece offset bucking ram with programmable rotation and deep retraction; vision system for automatic parts program re-synchronization and part edge margin control; and an automatic rivet selection/handling system.

  20. Selective targeting of TRPV1 expressing sensory nerve terminals in the spinal cord for long lasting analgesia.

    Directory of Open Access Journals (Sweden)

    Joseph A Jeffry

    Full Text Available Chronic pain is a major clinical problem and opiates are often the only treatment, but they cause significant problems ranging from sedation to deadly respiratory depression. Resiniferatoxin (RTX, a potent agonist of Transient Receptor Potential Vanilloid 1 (TRPV1, causes a slow, sustained and irreversible activation of TRPV1 and increases the frequency of spontaneous excitatory postsynaptic currents, but causes significant depression of evoked EPSCs due to nerve terminal depolarization block. Intrathecal administration of RTX to rats in the short-term inhibits nociceptive synaptic transmission, and in the long-term causes a localized, selective ablation of TRPV1-expressing central sensory nerve terminals leading to long lasting analgesia in behavioral models. Since RTX actions are selective for central sensory nerve terminals, other efferent functions of dorsal root ganglion neurons can be preserved. Preventing nociceptive transmission at the level of the spinal cord can be a useful strategy to treat chronic, debilitating and intractable pain.

  1. 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.

  2. Positive Selection in Bone Morphogenetic Protein 15 Targets a Natural Mutation Associated with Primary Ovarian Insufficiency in Human