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. 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...... interactive software is also part of a computer-assisted learning program on digital photogrammetry....

  3. 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.

  4. Automatic target identification using neural networks

    Science.gov (United States)

    Abdallah, Mahmoud A.; Samu, Tayib I.; Grissom, William A.

    1995-10-01

    Neural network theories are applied to attain human-like performance in areas such as speech recognition, statistical mapping, and target recognition or identification. In target identification, one of the difficult tasks has been the extraction of features to be used to train the neural network which is subsequently used for the target's identification. The purpose of this paper is to describe the development of an automatic target identification system using features extracted from a specific class of targets. The extracted features were the graphical representations of the silhouettes of the targets. Image processing techniques and some Fast Fourier Transform (FFT) properties were implemented to extract the features. The FFT eliminates variations in the extracted features due to rotation or scaling. A Neural Network was trained with the extracted features using the Learning Vector Quantization paradigm. An identification system was set up to test the algorithm. The image processing software was interfaced with MATLAB Neural Network Toolbox via a computer program written in C language to automate the target identification process. The system performed well as at classified the objects used to train it irrespective of rotation, scaling, and translation. This automatic target identification system had a classification success rate of about 95%.

  5. Automatic measurement of target crossing speed

    Science.gov (United States)

    Wardell, Mark; Lougheed, James H.

    1992-11-01

    The motion of ground vehicle targets after a ballistic round is launched can be a major source of inaccuracy for small (handheld) anti-armour weapon systems. A method of automatically measuring the crossing component to compensate the fire control solution has been devised and tested against various targets in a range of environments. A photodetector array aligned with the sight's horizontal reticle obtains scene features, which are digitized and processed to separate target from sight motion. Relative motion of the target against the background is briefly monitored to deduce angular crossing rate and a compensating lead angle is introduced into the aim point. Research to gather quantitative data and optimize algorithm performance is described, and some results from field testing are presented.

  6. 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

  7. A Context Dependent Automatic Target Recognition System

    Science.gov (United States)

    Kim, J. H.; Payton, D. W.; Olin, K. E.; Tseng, D. Y.

    1984-06-01

    This paper describes a new approach to automatic target recognizer (ATR) development utilizing artificial intelligent techniques. The ATR system exploits contextual information in its detection and classification processes to provide a high degree of robustness and adaptability. In the system, knowledge about domain objects and their contextual relationships is encoded in frames, separating it from low level image processing algorithms. This knowledge-based system demonstrates an improvement over the conventional statistical approach through the exploitation of diverse forms of knowledge in its decision-making process.

  8. Burglar Target Selection

    Science.gov (United States)

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

    2015-01-01

    Objectives: This study builds on research undertaken by Bernasco and Nieuwbeerta and explores the generalizability of a theoretically derived offender target selection model in three cross-national study regions. Methods: Taking a discrete spatial choice approach, we estimate the impact of both environment- and offender-level factors on residential burglary placement in the Netherlands, the United Kingdom, and Australia. Combining cleared burglary data from all study regions in a single statistical model, we make statistical comparisons between environments. Results: In all three study regions, the likelihood an offender selects an area for burglary is positively influenced by proximity to their home, the proportion of easily accessible targets, and the total number of targets available. Furthermore, in two of the three study regions, juvenile offenders under the legal driving age are significantly more influenced by target proximity than adult offenders. Post hoc tests indicate the magnitudes of these impacts vary significantly between study regions. Conclusions: While burglary target selection strategies are consistent with opportunity-based explanations of offending, the impact of environmental context is significant. As such, the approach undertaken in combining observations from multiple study regions may aid criminology scholars in assessing the generalizability of observed findings across multiple environments. PMID:25866418

  9. Towards Automatic Decentralized Control Structure Selection

    DEFF Research Database (Denmark)

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

  10. Towards Automatic Decentralized Control Structure Selection

    DEFF Research Database (Denmark)

    Jørgensen, John Bagterp; Jørgensen, Sten Bay

    2000-01-01

    A subtask in integration of design and control of chemical processes is the selection of a control structure. Automating the selection of the control structure enables sequential integration of process and control design. As soon as the process is specified or computed, a structure for decentrali......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...

  11. CDTI target selection criteria

    Science.gov (United States)

    Britt, C. L.; Davis, C. M.; Jackson, C. B.; Mcclellan, V. A.

    1984-01-01

    A Cockpit Display of Traffic Information (CDTI) is a cockpit instrument which provides information to the aircrew on the relative location of aircraft traffic in the vicinity of their aircraft (township). In addition, the CDTI may provide information to assist in navigation and in aircraft control. It is usually anticipated that the CDTI will be integrated with a horizontal situation indicator used for navigational purposes and/or with a weather radar display. In this study, several sets of aircraft traffic data are analyzed to determine statistics on the number of targets that will be displayed on a CDTI using various target selection criteria. Traffic data were obtained from an Atlanta Terminal Area Simulation and from radar tapes recorded at the Atlanta and Miami terminal areas. Results are given in the form of plots showing the average percentage of time (or probability) that an aircraft equipped with a CDTI would observe from 0 to 10 other aircraft on the display for range settings on the CDTI up to 30 n. mi. and using various target discrimination techniques.

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

    Science.gov (United States)

    Amit, Guy; Purdie, Thomas G; Levinshtein, Alex; Hope, Andrew J; Lindsay, Patricia; Marshall, Andrea; Jaffray, David A; Pekar, Vladimir

    2015-04-01

    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. 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. 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 coverage and organ at risk

  13. Automatic target extraction in complicated background for camera calibration

    Science.gov (United States)

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

    2016-03-01

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

  14. Automatic targeting of plasma spray gun

    International Nuclear Information System (INIS)

    Abbatiello, L.A.; Neal, R.E.

    1978-01-01

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

  15. Artificial Intelligence In Automatic Target Recognizers: Technology And Timelines

    Science.gov (United States)

    Gilmore, John F.

    1984-12-01

    The recognition of targets in thermal imagery has been a problem exhaustively analyzed in its current localized dimension. This paper discusses the application of artificial intelligence (AI) technology to automatic target recognition, a concept capable of expanding current ATR efforts into a new globalized dimension. Deficiencies of current automatic target recognition systems are reviewed in terms of system shortcomings. Areas of artificial intelligence which show the most promise in improving ATR performance are analyzed, and a timeline is formed in light of how near (as well as far) term artificial intelligence applications may exist. Current research in the area of high level expert vision systems is reviewed and the possible utilization of artificial intelligence architectures to improve low level image processing functions is also discussed. Additional application areas of relevance to solving the problem of automatic target recognition utilizing both high and low level processing are also explored.

  16. Automatic Target Recognition for Hyperspectral Imagery

    Science.gov (United States)

    2012-03-01

    D., Rossacci, M., Lockwood, R., Cooley, T., & Jacobson, J. Maintaining CFAR Operation in Hyperspectral Target Detection Using Extreme Value...Multiple-Band CFAR Detection of an Optical Pattern with Unknown Spectral Distribution. IEEE Transactions on Acoustics, Speech, and Signal Processing...F. C., Fuhrmann, D. R., Kelly, E. J., & Nitzburg, R. (1992). A CFAR adaptive matched filter detector. IEEE Transactions onAerospace and Electronic

  17. Demonstrator for Automatic Target Classification in SAR Imagery

    NARCIS (Netherlands)

    Wit, J.J.M. de; Broek, A.C. van den; Dekker, R.J.

    2006-01-01

    Due to the increasing use of unmanned aerial vehicles (UAV) for reconnaissance, surveillance, and target acquisition applications, the interest in synthetic aperture radar (SAR) systems is growing. In order to facilitate the processing of the enormous amount of SAR data on the ground, automatic

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

    International Nuclear Information System (INIS)

    Singleton, R.M.; Perkins, D.E.; Willenborg, D.L.

    1980-01-01

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

  19. 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

  20. Advanced automatic target recognition for police helicopter missions

    Science.gov (United States)

    Stahl, Christoph; Schoppmann, Paul

    2000-08-01

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

  1. The role of situational awareness in automatic target recognition

    Science.gov (United States)

    Snorrason, Magnus S.; Goodsell, Thom R.; Monnier, Camille R.; Stevens, Mark R.

    2004-09-01

    Model-based Automatic Target Recognition (ATR) algorithms are adept at recognizing targets in high fidelity 3D LADAR imagery. Most current approaches involve a matching component where a hypothesized target and target pose are iteratively aligned to pre-segmented range data. Once the model-to-data alignment has converged, a match score is generated indicating the quality of match. This score is then used to rank one model hypothesis over another. The main drawback of this approach is twofold. First, to ensure the correct target is recognized, a large number of model hypotheses must be considered. Even with a highly accurate indexing algorithm, the number of target types and variants that need to be explored is prohibitive for real-time operation. Second, the iterative matching step must consider a variety of target poses to ensure that the correct alignment is recovered. Inaccurate alignments produce erroneous match scores and thus errors when ranking one target hypothesis over another. To compensate for such drawbacks, we explore the use of situational awareness information already available to an image analyst. Examples of such information include knowledge of the surrounding terrain (to assess potential occlusion levels) and targets of interest (to account for target variants).

  2. Channel selection for automatic seizure detection

    DEFF Research Database (Denmark)

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

    2012-01-01

    Objective: To investigate the performance of epileptic seizure detection using only a few of the recorded EEG channels and the ability of software to select these channels compared with a neurophysiologist. Methods: Fifty-nine seizures and 1419 h of interictal EEG are used for training and testing...

  3. 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....

  4. Automatic system of production, transfer and processing of coin targets for the production of metallic radioisotopes

    Science.gov (United States)

    Pellicioli, M.; Ouadi, A.; Marchand, P.; Foehrenbacher, T.; Schuler, J.; Dick-Schuler, N.; Brasse, D.

    2017-05-01

    The work presented in this paper gathers three main technical developments aiming at 1) optimizing nuclide production by the mean of solid targets 2) automatically transferring coin targets from vault to hotcell without human intervention 3) processing target dilution and purification in hotcell automatically. This system has been installed on a ACSI TR24 cyclotron in Strasbourg France.

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

    Science.gov (United States)

    Chen, Xiaohan; Schmid, Natalia A.

    2010-04-01

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

  6. Real-time automatic target identification system for air-to-ground targeting

    Science.gov (United States)

    Nicholas, Mike; Wood, Jonathan; Nothard, Jo

    2005-10-01

    Future targeting systems, for manned or unmanned combat aircraft, aim to provide increased mission success and platform survivability by successfully detecting and identifying even difficult targets at very long ranges. One of the key enabling technologies for such systems is robust automatic target identification (ATI), operating on high resolution electro-optic sensor imagery. QinetiQ have developed a real time ATI processor which will be demonstrated with infrared imagery from the Wescam MX15 in airborne trials in summer 2005. This paper describes some of the novel ATI algorithms, the challenges overcome to port the ATI from the laboratory onto a real time system and offers an assessment of likely airborne performance based on analysis of synthetic image sequences.

  7. Automatic selection of region of interest for radiographic texture analysis

    Science.gov (United States)

    Lan, Li; Giger, Maryellen L.; Wilkie, Joel R.; Vokes, Tamara J.; Chen, Weijie; Li, Hui; Lyons, Tracy; Chinander, Michael R.; Pham, Ann

    2007-03-01

    We have been developing radiographic texture analysis (RTA) for assessing osteoporosis and the related risk of fracture. Currently, analyses are performed on heel images obtained from a digital imaging device, the GE/Lunar PIXI, that yields both the bone mineral density (BMD) and digital images (0.2-mm pixels; 12-bit quantization). RTA is performed on the image data in a region-of-interest (ROI) placed just below the talus in order to include the trabecular structure in the analysis. We have found that variations occur from manually selecting this ROI for RTA. To reduce the variations, we present an automatic method involving an optimized Canny edge detection technique and parameterized bone segmentation, to define bone edges for the placement of an ROI within the predominantly calcaneus portion of the radiographic heel image. The technique was developed using 1158 heel images and then tested on an independent set of 176 heel images. Results from a subjective analysis noted that 87.5% of ROI placements were rated as "good". In addition, an objective overlap measure showed that 98.3% of images had successful ROI placements as compared to placement by an experienced observer at an overlap threshold of 0.4. In conclusion, our proposed method for automatic ROI selection on radiographic heel images yields promising results and the method has the potential to reduce intra- and inter-observer variations in selecting ROIs for radiographic texture analysis.

  8. Stiffness and the automatic selection of ODE codes

    International Nuclear Information System (INIS)

    Shampine, L.F.

    1984-01-01

    The author describes the basic ideas behind the most popular methods for the numerical solution of ordinary differential equations (ODEs). He takes up the qualitative behavior of solutions of ODEs and its relation ot the propagation of numerical error. Codes for ODEs are intended either for stiff problems or for non-stiff problems. The difference is explained. Users of codes do not have the information needed to recognize stiffness. A code, DEASY, which automatically recognizes stiffness and selects a suitable method is described

  9. 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

  10. Morphometric Atlas Selection for Automatic Brachial Plexus Segmentation

    Energy Technology Data Exchange (ETDEWEB)

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

    2015-07-01

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

  11. Automatic phoneme category selectivity in the dorsal auditory stream.

    Science.gov (United States)

    Chevillet, Mark A; Jiang, Xiong; Rauschecker, Josef P; Riesenhuber, Maximilian

    2013-03-20

    Debates about motor theories of speech perception have recently been reignited by a burst of reports implicating premotor cortex (PMC) in speech perception. Often, however, these debates conflate perceptual and decision processes. Evidence that PMC activity correlates with task difficulty and subject performance suggests that PMC might be recruited, in certain cases, to facilitate category judgments about speech sounds (rather than speech perception, which involves decoding of sounds). However, it remains unclear whether PMC does, indeed, exhibit neural selectivity that is relevant for speech decisions. Further, it is unknown whether PMC activity in such cases reflects input via the dorsal or ventral auditory pathway, and whether PMC processing of speech is automatic or task-dependent. In a novel modified categorization paradigm, we presented human subjects with paired speech sounds from a phonetic continuum but diverted their attention from phoneme category using a challenging dichotic listening task. Using fMRI rapid adaptation to probe neural selectivity, we observed acoustic-phonetic selectivity in left anterior and left posterior auditory cortical regions. Conversely, we observed phoneme-category selectivity in left PMC that correlated with explicit phoneme-categorization performance measured after scanning, suggesting that PMC recruitment can account for performance on phoneme-categorization tasks. Structural equation modeling revealed connectivity from posterior, but not anterior, auditory cortex to PMC, suggesting a dorsal route for auditory input to PMC. Our results provide evidence for an account of speech processing in which the dorsal stream mediates automatic sensorimotor integration of speech and may be recruited to support speech decision tasks.

  12. 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.

  13. Target selection for direct marketing.

    NARCIS (Netherlands)

    Bult, Jan Roelf

    1993-01-01

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

  14. Automatized target devices for radioisotope production at the RITs cyclotron

    International Nuclear Information System (INIS)

    Bogdanov, P.V.; Ivanov, V.V.; Karasev, B.G.

    1981-01-01

    An automation target device intended for isotope production on the internal beam of the RITs cyclotron is decribed. The target device comprises the following main units: target head, vacuum lock, charging device, transport system for bringing the target for charging; mechanism of target discharge transport device, control interlocking and signalling control system of target radiation power. The automation target device permits radioisotope production on the cyclotron in commercial scales with automation substitution of irradiated targets. The time of substitution of one of six targets makes up only 5 min. The time of charging a new group of targets to the charge device - 60 min. Contact of the personnel with irradiated targets is practically excluded and the necessity of entering the cyclotron room for maintenance of the plant is reduced to the minimum [ru

  15. Selective Nanoparticle Targeting of the Renal Tubules.

    Science.gov (United States)

    Williams, Ryan M; Shah, Janki; Tian, Helen S; Chen, Xi; Geissmann, Frederic; Jaimes, Edgar A; Heller, Daniel A

    2018-01-01

    Direct targeting to the kidneys is a promising strategy to improve drug therapeutic index for the treatment of kidney diseases. We sought to investigate the renal selectivity and safety of kidney-targeted mesoscale nanoparticle technology. We found that direct intravenous administration of these particles resulted in 26-fold renal selectivity and localized negligibly in the liver or other organs. The nanoparticles targeted the renal proximal tubular epithelial cells, as evidenced by intravital microscopy and ex vivo imaging. Mice treated with the nanoparticles exhibited no negative systemic consequences, immune reaction, liver impairment, or renal impairment. The localization of material selectively to the renal tubules is uncommon, and this work portends the development of renal-targeted drugs for the treatment of kidney diseases. © 2017 American Heart Association, Inc.

  16. Selective targeting of epigenetic reader domains.

    Science.gov (United States)

    Greschik, Holger; Schüle, Roland; Günther, Thomas

    2017-05-01

    Epigenetic regulators including writers, erasers, and readers of chromatin marks have been implicated in numerous diseases and are therefore subject of intense academic and pharmaceutical research. While several small-molecule inhibitors targeting writers or erasers are either approved drugs or are currently being evaluated in clinical trials, the targeting of epigenetic readers has lagged behind. Proof-of-principle that epigenetic readers are also relevant drug targets was provided by landmark discoveries of selective inhibitors targeting the BET family of acetyl-lysine readers. More recently, high affinity chemical probes for non-BET acetyl- and methyl-lysine reader domains have also been developed. Areas covered: This article covers recent advances with the identification and validation of inhibitors and chemical probes targeting epigenetic reader domains. Issues related to epigenetic reader druggability, quality requirements for chemical probes, interpretation of cellular action, unexpected cross-talk, and future challenges are also discussed. Expert opinion: Chemical probes provide a powerful means to unravel biological functions of epigenetic readers and evaluate their potential as drug targets. To yield meaningful results, potency, selectivity, and cellular target engagement of chemical probes need to be stringently validated. Future chemical probes will probably need to fulfil additional criteria such as strict target specificity or the targeting of readers within protein complexes.

  17. 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.

  18. Automatic identification of non-reflective subsurface targets in radar sounder data based on morphological profile

    Science.gov (United States)

    Khodadadzadeh, Mahdi; Ilisei, Ana-Maria; Bruzzone, Lorenzo

    2017-10-01

    The amount of radar sounder data, which are used to analyze the subsurface of icy environments (e.g., Poles of Earth and Mars), is dramatically increasing from both airborne campaigns at the ice sheets and satellite missions on other planetary bodies. However, the main approach to the investigation of such data is by visual interpretation, which is subjective and time consuming. Moreover, the few available automatic techniques have been developed for analyzing highly reflective subsurface targets, e.g., ice layers, basal interface. Besides the high reflective targets, glaciologists have also shown great interest in the analysis of non-reflective targets, such as the echo-free zone in ice sheets, and the reflective free zone in the subsurface of the South Pole of Mars. However, in the literature, there is no dedicated automatic technique for the analysis of non-reflective targets. To address this limitation, we propose an automatic classification technique for the identification of non-reflective targets in radar sounder data. The method is made up of two steps, i.e., i) feature extraction, which is the core of the method, and ii) automatic classification of subsurface targets. We initially prove that the commonly employed features for the analysis of the radar signal (e.g., statistical and texture based features) are ineffective for the identification of non-reflective targets. Thus, for feature extraction, we propose to exploit structural information based on the morphological closing profile. We show the effectiveness of such features in discriminating of non-reflective target from the other ice subsurface targets. In the second step, a random forest classifier is used to perform the automatic classification. Our experimental results, conducted using two data sets from Central Antarctica and South Pole of Mars, point out the effectiveness of the proposed technique for the accurate identification of non-reflective targets.

  19. Clustered Multi-Task Learning for Automatic Radar Target Recognition.

    Science.gov (United States)

    Li, Cong; Bao, Weimin; Xu, Luping; Zhang, Hua

    2017-09-27

    Model training is a key technique for radar target recognition. Traditional model training algorithms in the framework of single task leaning ignore the relationships among multiple tasks, which degrades the recognition performance. In this paper, we propose a clustered multi-task learning, which can reveal and share the multi-task relationships for radar target recognition. To further make full use of these relationships, the latent multi-task relationships in the projection space are taken into consideration. Specifically, a constraint term in the projection space is proposed, the main idea of which is that multiple tasks within a close cluster should be close to each other in the projection space. In the proposed method, the cluster structures and multi-task relationships can be autonomously learned and utilized in both of the original and projected space. In view of the nonlinear characteristics of radar targets, the proposed method is extended to a non-linear kernel version and the corresponding non-linear multi-task solving method is proposed. Comprehensive experimental studies on simulated high-resolution range profile dataset and MSTAR SAR public database verify the superiority of the proposed method to some related algorithms.

  20. Automatic selective feature retention in patient specific elastic surface registration

    CSIR Research Space (South Africa)

    Jansen van Rensburg, GJ

    2011-01-01

    Full Text Available . An intelligent mesh morphing strategy where dissimilar feature surfaces can be extracted automatically also greatly reduces the amount of user input required. REFERENCES [1] R. Bryan, P.S. Mohan, A. Hopkins, F. Galloway, M. Taylor and P. Nair, Statitical...

  1. 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.

  2. 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.

  3. Improved Local Ternary Patterns for Automatic Target Recognition in Infrared Imagery

    Directory of Open Access Journals (Sweden)

    Xiaosheng Wu

    2015-03-01

    Full Text Available This paper presents an improved local ternary pattern (LTP for automatic target recognition (ATR in infrared imagery. Firstly, a robust LTP (RLTP scheme is proposed to overcome the limitation of the original LTP for achieving the invariance with respect to the illumination transformation. Then, a soft concave-convex partition (SCCP is introduced to add some flexibility to the original concave-convex partition (CCP scheme. Referring to the orthogonal combination of local binary patterns (OC_LBP, the orthogonal combination of LTP (OC_LTP is adopted to reduce the dimensionality of the LTP histogram. Further, a novel operator, called the soft concave-convex orthogonal combination of robust LTP (SCC_OC_RLTP, is proposed by combing RLTP, SCCP and OC_LTP. Finally, the new operator is used for ATR along with a blocking schedule to improve its discriminability and a feature selection technique to enhance its efficiency. Experimental results on infrared imagery show that the proposed features can achieve competitive ATR results compared with the state-of-the-art methods.

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

    Science.gov (United States)

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

    2017-06-01

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

  5. Computationally Efficient Automatic Coast Mode Target Tracking Based on Occlusion Awareness in Infrared Images.

    Science.gov (United States)

    Kim, Sohyun; Jang, Gwang-Il; Kim, Sungho; Kim, Junmo

    2018-03-27

    This paper proposes the automatic coast mode tracking of centroid trackers for infrared images to overcome the target occlusion status. The centroid tracking method, using only the brightness information of an image, is still widely used in infrared imaging tracking systems because it is difficult to extract meaningful features from infrared images. However, centroid trackers are likely to lose the track because they are highly vulnerable to screened status by the clutter or background. Coast mode, one of the tracking modes, maintains the servo slew rate with the tracking rate right before the loss of track. The proposed automatic coast mode tracking method makes decisions regarding entering coast mode by the prediction of target occlusion and tries to re-lock the target and resume the tracking after blind time. This algorithm comprises three steps. The first step is the prediction process of the occlusion by checking both matters which have target-likelihood brightness and which may screen the target despite different brightness. The second step is the process making inertial tracking commands to the servo. The last step is the process of re-locking a target based on the target modeling of histogram ratio. The effectiveness of the proposed algorithm is addressed by presenting experimental results based on computer simulation with various test imagery sequences compared to published tracking algorithms. The proposed algorithm is tested under a real environment with a naval electro-optical tracking system (EOTS) and airborne EO/IR system.

  6. Computationally Efficient Automatic Coast Mode Target Tracking Based on Occlusion Awareness in Infrared Images

    Directory of Open Access Journals (Sweden)

    Sohyun Kim

    2018-03-01

    Full Text Available This paper proposes the automatic coast mode tracking of centroid trackers for infrared images to overcome the target occlusion status. The centroid tracking method, using only the brightness information of an image, is still widely used in infrared imaging tracking systems because it is difficult to extract meaningful features from infrared images. However, centroid trackers are likely to lose the track because they are highly vulnerable to screened status by the clutter or background. Coast mode, one of the tracking modes, maintains the servo slew rate with the tracking rate right before the loss of track. The proposed automatic coast mode tracking method makes decisions regarding entering coast mode by the prediction of target occlusion and tries to re-lock the target and resume the tracking after blind time. This algorithm comprises three steps. The first step is the prediction process of the occlusion by checking both matters which have target-likelihood brightness and which may screen the target despite different brightness. The second step is the process making inertial tracking commands to the servo. The last step is the process of re-locking a target based on the target modeling of histogram ratio. The effectiveness of the proposed algorithm is addressed by presenting experimental results based on computer simulation with various test imagery sequences compared to published tracking algorithms. The proposed algorithm is tested under a real environment with a naval electro-optical tracking system (EOTS and airborne EO/IR system.

  7. Selective targeting of microglia by quantum dots

    Directory of Open Access Journals (Sweden)

    Minami S Sakura

    2012-01-01

    Full Text Available Abstract Background Microglia, the resident immune cells of the brain, have been implicated in brain injury and various neurological disorders. However, their precise roles in different pathophysiological situations remain enigmatic and may range from detrimental to protective. Targeting the delivery of biologically active compounds to microglia could help elucidate these roles and facilitate the therapeutic modulation of microglial functions in neurological diseases. Methods Here we employ primary cell cultures and stereotaxic injections into mouse brain to investigate the cell type specific localization of semiconductor quantum dots (QDs in vitro and in vivo. Two potential receptors for QDs are identified using pharmacological inhibitors and neutralizing antibodies. Results In mixed primary cortical cultures, QDs were selectively taken up by microglia; this uptake was decreased by inhibitors of clathrin-dependent endocytosis, implicating the endosomal pathway as the major route of entry for QDs into microglia. Furthermore, inhibiting mannose receptors and macrophage scavenger receptors blocked the uptake of QDs by microglia, indicating that QD uptake occurs through microglia-specific receptor endocytosis. When injected into the brain, QDs were taken up primarily by microglia and with high efficiency. In primary cortical cultures, QDs conjugated to the toxin saporin depleted microglia in mixed primary cortical cultures, protecting neurons in these cultures against amyloid beta-induced neurotoxicity. Conclusions These findings demonstrate that QDs can be used to specifically label and modulate microglia in primary cortical cultures and in brain and may allow for the selective delivery of therapeutic agents to these cells.

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

    DEFF Research Database (Denmark)

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

    An approach to use the available agricultural parcel information to automatically select training samples for crop classification is investigated. Previous research addressed the multi-evidence crop classification approach using an ensemble classifier. This first produced confidence measures using...... 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...... approach is named as ECRA (Ensemble based Cluster Refinement Approach). ECRA first automatically removes mislabeled samples and then selects the refined training samples in an iterative training-reclassification scheme. Mislabel removal is based on the expectation that mislabels in each class will be far...

  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...

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

    International Nuclear Information System (INIS)

    Claverie, G.

    1996-01-01

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

  11. Progressive sampling-based Bayesian optimization for efficient and automatic machine learning model selection.

    Science.gov (United States)

    Zeng, Xueqiang; Luo, Gang

    2017-12-01

    Machine learning is broadly used for clinical data analysis. Before training a model, a machine learning algorithm must be selected. Also, the values of one or more model parameters termed hyper-parameters must be set. Selecting algorithms and hyper-parameter values requires advanced machine learning knowledge and many labor-intensive manual iterations. To lower the bar to machine learning, miscellaneous automatic selection methods for algorithms and/or hyper-parameter values have been proposed. Existing automatic selection methods are inefficient on large data sets. This poses a challenge for using machine learning in the clinical big data era. To address the challenge, this paper presents progressive sampling-based Bayesian optimization, an efficient and automatic selection method for both algorithms and hyper-parameter values. We report an implementation of the method. We show that compared to a state of the art automatic selection method, our method can significantly reduce search time, classification error rate, and standard deviation of error rate due to randomization. This is major progress towards enabling fast turnaround in identifying high-quality solutions required by many machine learning-based clinical data analysis tasks.

  12. 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...... 4 other common automatic feature selection algorithms: Backward selection, forward selection, NLPCA and PCA as well as using no algorithms at all. The benchmarking will be performed through two experiments with two different data sets that are both time-series regression-based problems...... selection algorithms that can be used for many different applications....

  13. Extracting contextual information in digital imagery: applications to automatic target recognition and mammography

    Science.gov (United States)

    Spence, Clay D.; Sajda, Paul; Pearson, John C.

    1996-02-01

    An important problem in image analysis is finding small objects in large images. The problem is challenging because (1) searching a large image is computationally expensive, and (2) small targets (on the order of a few pixels in size) have relatively few distinctive features which enable them to be distinguished from non-targets. To overcome these challenges we have developed a hierarchical neural network (HNN) architecture which combines multi-resolution pyramid processing with neural networks. The advantages of the architecture are: (1) both neural network training and testing can be done efficiently through coarse-to-fine techniques, and (2) such a system is capable of learning low-resolution contextual information to facilitate the detection of small target objects. We have applied this neural network architecture to two problems in which contextual information appears to be important for detecting small targets. The first problem is one of automatic target recognition (ATR), specifically the problem of detecting buildings in aerial photographs. The second problem focuses on a medical application, namely searching mammograms for microcalcifications, which are cues for breast cancer. Receiver operating characteristic (ROC) analysis suggests that the hierarchical architecture improves the detection accuracy for both the ATR and microcalcification detection problems, reducing false positive rates by a significant factor. In addition, we have examined the hidden units at various levels of the processing hierarchy and found what appears to be representations of road location (for the ATR example) and ductal/vasculature location (for mammography), both of which are in agreement with the contextual information used by humans to find these classes of targets. We conclude that this hierarchical neural network architecture is able to automatically extract contextual information in imagery and utilize it for target detection.

  14. Linking Target Selection to Political Objectives

    National Research Council Canada - National Science Library

    Tew, Scott

    2002-01-01

    ... up for effect, Our goal is to find and effect the targets that will ultimately lead to attainment of our political objectives Yet, how do we logically link a target to the desired political objectives...

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

    Directory of Open Access Journals (Sweden)

    Silvia Francesca eStorti

    2013-05-01

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

  16. 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...

  17. 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

    available, identifying the most-informative RT is becoming increasingly difficult. Previous studies on the selection of RT have provided guidelines for manual taxon selection, and for eliminating closely related taxa. However, no general strategy for automatic selection of RT is currently available. Results......: 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...

  18. SYSTEM FOR AUTOMATIC SELECTION OF THE SPEED RATE OF ELECTRIC VEHICLES FOR REDUCING THE POWER CONSUMPTION

    Directory of Open Access Journals (Sweden)

    K. O. Soroka

    2017-06-01

    Full Text Available Purpose. The work is aimed to design a system for automatic selection of the optimal traffic modes and automatic monitoring of the electric energy consumption by electric transport. This automatic system should provide for the minimum energy expenses. Methodology. Current methodologies: 1 mathematical modeling of traffic modes of ground electric vehicles; 2 comparison of modelling results with the statistical monitoring; 3 system development for automatic choice of traffic modes of electric transport with minimal electrical energy consumptions taking into account the given route schedules and the limitations imposed by the general traffic rules. Findings. The authors obtained a mathematical dependency of the energy consumption by electric transport enterprises on the monthly averaged environment temperature was obtained. A system which allows for an automatic selection of the speed limit and provides automatic monitoring of the electrical energy consumption by electric vehicles was proposed in the form of local network, which works together with existing GPS system. Originality. A mathematical model for calculating the motion curves and energy consumption of electric vehicles has been developed. This model takes into account the characteristic values of the motor engine and the steering system, the change of the mass when loading or unloading passengers, the slopes and radii of the roads, the limitations given by the general traffic rules, and other factors. The dependency of the energy consumption on the averaged monthly environment temperature for public electric transport companies has been calculated. Practical value. The developed mathematical model simplifies the calculations of the traffic dynamics and energy consumption. It can be used for calculating the routing maps, for design and upgrade of the power networks, for development of the electricity saving measures. The system simplifies the work of the vehicle driver and allows reducing

  19. Fully automatic time-window selection using machine learning for global adjoint tomography

    Science.gov (United States)

    Chen, Y.; Hill, J.; Lei, W.; Lefebvre, M. P.; Bozdag, E.; Komatitsch, D.; Tromp, J.

    2017-12-01

    Selecting time windows from seismograms such that the synthetic measurements (from simulations) and measured observations are sufficiently close is indispensable in a global adjoint tomography framework. The increasing amount of seismic data collected everyday around the world demands "intelligent" algorithms for seismic window selection. While the traditional FLEXWIN algorithm can be "automatic" to some extent, it still requires both human input and human knowledge or experience, and thus is not deemed to be fully automatic. The goal of intelligent window selection is to automatically select windows based on a learnt engine that is built upon a huge number of existing windows generated through the adjoint tomography project. We have formulated the automatic window selection problem as a classification problem. All possible misfit calculation windows are classified as either usable or unusable. Given a large number of windows with a known selection mode (select or not select), we train a neural network to predict the selection mode of an arbitrary input window. Currently, the five features we extract from the windows are its cross-correlation value, cross-correlation time lag, amplitude ratio between observed and synthetic data, window length, and minimum STA/LTA value. More features can be included in the future. We use these features to characterize each window for training a multilayer perceptron neural network (MPNN). Training the MPNN is equivalent to solve a non-linear optimization problem. We use backward propagation to derive the gradient of the loss function with respect to the weighting matrices and bias vectors and use the mini-batch stochastic gradient method to iteratively optimize the MPNN. Numerical tests show that with a careful selection of the training data and a sufficient amount of training data, we are able to train a robust neural network that is capable of detecting the waveforms in an arbitrary earthquake data with negligible detection error

  20. 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.)

  1. Improving SAR Automatic Target Recognition Models with Transfer Learning from Simulated Data

    DEFF Research Database (Denmark)

    Malmgren-Hansen, David; Kusk, Anders; Dall, Jørgen

    2017-01-01

    SAR images of sufficient size, simulated data play a big role in SAR ATR development, but the transferability of knowledge learned on simulated data to real data remains to be studied further. In this letter, we show the first study of Transfer Learning between a simulated data set and a set of real....... These results encourage SAR ATR development to continue the improvement of simulated data sets of greater size and complex scenarios in order to build robust algorithms for real life SAR ATR applications.......Data-driven classification algorithms have proved to do well for automatic target recognition (ATR) in synthetic aperture radar (SAR) data. Collecting data sets suitable for these algorithms is a challenge in itself as it is difficult and expensive. Due to the lack of labeled data sets with real...

  2. 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.

  3. Automatic vibration mode selection and excitation; combining modal filtering with autoresonance

    Science.gov (United States)

    Davis, Solomon; Bucher, Izhak

    2018-02-01

    Autoresonance is a well-known nonlinear feedback method used for automatically exciting a system at its natural frequency. Though highly effective in exciting single degree of freedom systems, in its simplest form it lacks a mechanism for choosing the mode of excitation when more than one is present. In this case a single mode will be automatically excited, but this mode cannot be chosen or changed. In this paper a new method for automatically exciting a general second-order system at any desired natural frequency using Autoresonance is proposed. The article begins by deriving a concise expression for the frequency of the limit cycle induced by an Autoresonance feedback loop enclosed on the system. The expression is based on modal decomposition, and provides valuable insight into the behavior of a system controlled in this way. With this expression, a method for selecting and exciting a desired mode naturally follows by combining Autoresonance with Modal Filtering. By taking various linear combinations of the sensor signals, by orthogonality one can "filter out" all the unwanted modes effectively. The desired mode's natural frequency is then automatically reflected in the limit cycle. In experiment the technique has proven extremely robust, even if the amplitude of the desired mode is significantly smaller than the others and the modal filters are greatly inaccurate.

  4. 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.

  5. 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. © 2014 The Author(s). Evolution © 2014 The Society for the Study of Evolution.

  6. Sexual selection targets cetacean pelvic bones

    Science.gov (United States)

    Dines, J. P.; Otárola-Castillo, E.; Ralph, P.; Alas, J.; Daley, T.; Smith, A. D.; Dean, M. D.

    2014-01-01

    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 which 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) have evolved relatively large penises and pelvic bones compared to their body size, and 2) pelvic bone shape diverges more quickly in species pairs that have diverged in inferred mating system. Neither pattern was observed in the anterior-most pair of vertebral ribs, which served as a negative control. This study provides evidence that sexual selection can affect internal anatomy that controls male genitalia. These important functions may explain why cetacean pelvic bones have not been lost through evolutionary time. PMID:25186496

  7. A multimodality segmentation framework for automatic target delineation in head and neck radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Yang, Jinzhong; Aristophanous, Michalis, E-mail: MAristophanous@mdanderson.org [Department of Radiation Physics, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Beadle, Beth M.; Garden, Adam S. [Department of Radiation Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas 77030 (United States); Schwartz, David L. [Department of Radiation Oncology, The University of Texas Southwestern Medical Center, Dallas, Texas 75390 (United States)

    2015-09-15

    Purpose: To develop an automatic segmentation algorithm integrating imaging information from computed tomography (CT), positron emission tomography (PET), and magnetic resonance imaging (MRI) to delineate target volume in head and neck cancer radiotherapy. Methods: Eleven patients with unresectable disease at the tonsil or base of tongue who underwent MRI, CT, and PET/CT within two months before the start of radiotherapy or chemoradiotherapy were recruited for the study. For each patient, PET/CT and T1-weighted contrast MRI scans were first registered to the planning CT using deformable and rigid registration, respectively, to resample the PET and magnetic resonance (MR) images to the planning CT space. A binary mask was manually defined to identify the tumor area. The resampled PET and MR images, the planning CT image, and the binary mask were fed into the automatic segmentation algorithm for target delineation. The algorithm was based on a multichannel Gaussian mixture model and solved using an expectation–maximization algorithm with Markov random fields. To evaluate the algorithm, we compared the multichannel autosegmentation with an autosegmentation method using only PET images. The physician-defined gross tumor volume (GTV) was used as the “ground truth” for quantitative evaluation. Results: The median multichannel segmented GTV of the primary tumor was 15.7 cm{sup 3} (range, 6.6–44.3 cm{sup 3}), while the PET segmented GTV was 10.2 cm{sup 3} (range, 2.8–45.1 cm{sup 3}). The median physician-defined GTV was 22.1 cm{sup 3} (range, 4.2–38.4 cm{sup 3}). The median difference between the multichannel segmented and physician-defined GTVs was −10.7%, not showing a statistically significant difference (p-value = 0.43). However, the median difference between the PET segmented and physician-defined GTVs was −19.2%, showing a statistically significant difference (p-value =0.0037). The median Dice similarity coefficient between the multichannel segmented

  8. 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

    2016-03-01

    On-board magnetic resonance (MR) image guidance during radiation therapy offers the potential for more accurate treatment delivery. To utilize the real-time image information, a crucial prerequisite is the ability to successfully segment and track regions of interest (ROI). The purpose of this work is to evaluate the performance of different segmentation algorithms using motion images (4 frames per second) acquired using a MR image-guided radiotherapy (MR-IGRT) system. Manual contours 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 (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 different methods for optimal segmentation with the on-board MR

  9. Pipe leak diagnostic using high frequency piezoelectric pressure sensor and automatic selection of intrinsic mode function

    Science.gov (United States)

    Yusop, Hanafi M.; Ghazali, M. F.; Yusof, M. F. M.; Remli, M. A. Pi; Kamarulzaman, M. H.

    2017-10-01

    In a recent study, the analysis of pressure transient signals could be seen as an accurate and low-cost method for leak and feature detection in water distribution systems. Transient phenomena occurs due to sudden changes in the fluid’s propagation in pipelines system caused by rapid pressure and flow fluctuation due to events such as closing and opening valves rapidly or through pump failure. In this paper, the feasibility of the Hilbert-Huang transform (HHT) method/technique in analysing the pressure transient signals in presented and discussed. HHT is a way to decompose a signal into intrinsic mode functions (IMF). However, the advantage of HHT is its difficulty in selecting the suitable IMF for the next data postprocessing method which is Hilbert Transform (HT). This paper reveals that utilizing the application of an integrated kurtosis-based algorithm for a z-filter technique (I-Kaz) to kurtosis ratio (I-Kaz-Kurtosis) allows/contributes to/leads to automatic selection of the IMF that should be used. This technique is demonstrated on a 57.90-meter medium high-density polyethylene (MDPE) pipe installed with a single artificial leak. The analysis results using the I-Kaz-kurtosis ratio revealed/confirmed that the method can be used as an automatic selection of the IMF although the noise level ratio of the signal is low. Therefore, the I-Kaz-kurtosis ratio method is recommended as a means to implement an automatic selection technique of the IMF for HHT analysis.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    International Nuclear Information System (INIS)

    Carlin, Jeffrey L.; Newberg, Heidi Jo; Lépine, Sébastien; Deng Licai; Chen Yuqin; Fu Xiaoting; Gao Shuang; Li Jing; Liu Chao; Beers, Timothy C.; Christlieb, Norbert; Grillmair, Carl J.; Guhathakurta, Puragra; Han Zhanwen; Hou Jinliang; Lee, Hsu-Tai; Liu Xiaowei; Pan Kaike; Sellwood, J. A.; Wang Hongchi

    2012-01-01

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

  12. Target Selection Models with Preference Variation Between Offenders

    NARCIS (Netherlands)

    Townsley, Michael; Birks, Daniel; Ruiter, Stijn; Bernasco, Wim; White, Gentry

    2016-01-01

    Objectives: This study explores preference variation in location choice strategies of residential burglars. Applying a model of offender target selection that is grounded in assertions of the routine activity approach, rational choice perspective, crime pattern and social disorganization theories,

  13. 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.

  14. 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.

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

    International Nuclear Information System (INIS)

    Jordan, C.W.; Cameron, G.R.; Krenik, R.M.; Crane, J.K.

    1981-01-01

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

  16. Atlas ranking and selection for automatic segmentation of the esophagus from CT scans

    Science.gov (United States)

    Yang, Jinzhong; Haas, Benjamin; Fang, Raymond; Beadle, Beth M.; Garden, Adam S.; Liao, Zhongxing; Zhang, Lifei; Balter, Peter; Court, Laurence

    2017-12-01

    In radiation treatment planning, the esophagus is an important organ-at-risk that should be spared in patients with head and neck cancer or thoracic cancer who undergo intensity-modulated radiation therapy. However, automatic segmentation of the esophagus from CT scans is extremely challenging because of the structure’s inconsistent intensity, low contrast against the surrounding tissues, complex and variable shape and location, and random air bubbles. The goal of this study is to develop an online atlas selection approach to choose a subset of optimal atlases for multi-atlas segmentation to the delineate esophagus automatically. We performed atlas selection in two phases. In the first phase, we used the correlation coefficient of the image content in a cubic region between each atlas and the new image to evaluate their similarity and to rank the atlases in an atlas pool. A subset of atlases based on this ranking was selected, and deformable image registration was performed to generate deformed contours and deformed images in the new image space. In the second phase of atlas selection, we used Kullback-Leibler divergence to measure the similarity of local-intensity histograms between the new image and each of the deformed images, and the measurements were used to rank the previously selected atlases. Deformed contours were overlapped sequentially, from the most to the least similar, and the overlap ratio was examined. We further identified a subset of optimal atlases by analyzing the variation of the overlap ratio versus the number of atlases. The deformed contours from these optimal atlases were fused together using a modified simultaneous truth and performance level estimation algorithm to produce the final segmentation. The approach was validated with promising results using both internal data sets (21 head and neck cancer patients and 15 thoracic cancer patients) and external data sets (30 thoracic patients).

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

    Directory of Open Access Journals (Sweden)

    Mukta Majumder

    2014-12-01

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

  18. Novel target configurations for selective ionization state studies in molybdenum

    International Nuclear Information System (INIS)

    Ilcisin, K.J.; Feldman, U.; Schwob, J.L.; Wouters, A.; Suckewer, S.; Princeton Univ., NJ

    1990-03-01

    Details of experiments aimed at achieving low ionization state selectivity in molybdenum are presented. Targets are excited with a 10 J CO 2 laser and the resultant VUV spectrum (300--700 Angstrom) has been studied. Combinations of focal spot size, target depth, and target geometries are compared. Simple attenuation of energy is shown not to vary ionization stage composition significantly. Experiments conducted with grazing incidence targets result only in a hot plasma. Modular targets with cooling cylinders of various radii demonstrated good selectivity of the ionization states, but with low absolute signals. Finally, results from combinations of focal spot adjustment and radiative cooling illustrate increased control over desired plasma temperature and density for spectroscopic studies of molybdenum. 7 refs., 14 figs

  19. Selection and Identification of Skeletal-Muscle-Targeted RNA Aptamers

    Directory of Open Access Journals (Sweden)

    Styliana Philippou

    2018-03-01

    Full Text Available Oligonucleotide gene therapy has shown great promise for the treatment of muscular dystrophies. Nevertheless, the selective delivery to affected muscles has shown to be challenging because of their high representation in the body and the high complexity of their cell membranes. Current trials show loss of therapeutic molecules to non-target tissues leading to lower target efficacy. Therefore, strategies that increase uptake efficiency would be particularly compelling. To address this need, we applied a cell-internalization SELEX (Systematic Evolution of Ligands by Exponential Enrichment approach and identified a skeletal muscle-specific RNA aptamer. A01B RNA aptamer preferentially internalizes in skeletal muscle cells and exhibits decreased affinity for off-target cells. Moreover, this in vitro selected aptamer retained its functionality in vivo, suggesting a potential new approach for targeting skeletal muscles. Ultimately, this will aid in the development of targeted oligonucleotide therapies against muscular dystrophies.

  20. In-silico Leishmania Target Selectivity of Antiparasitic Terpenoids

    Directory of Open Access Journals (Sweden)

    Ifedayo Victor Ogungbe

    2013-07-01

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

  1. Improved targeted immunization strategies based on two rounds of selection

    Science.gov (United States)

    Xia, Ling-Ling; Song, Yu-Rong; Li, Chan-Chan; Jiang, Guo-Ping

    2018-04-01

    In the case of high degree targeted immunization where the number of vaccine is limited, when more than one node associated with the same degree meets the requirement of high degree centrality, how can we choose a certain number of nodes from those nodes, so that the number of immunized nodes will not exceed the limit? In this paper, we introduce a new idea derived from the selection process of second-round exam to solve this problem and then propose three improved targeted immunization strategies. In these proposed strategies, the immunized nodes are selected through two rounds of selection, where we increase the quotas of first-round selection according the evaluation criterion of degree centrality and then consider another characteristic parameter of node, such as node's clustering coefficient, betweenness and closeness, to help choose targeted nodes in the second-round selection. To validate the effectiveness of the proposed strategies, we compare them with the degree immunizations including the high degree targeted and the high degree adaptive immunizations using two metrics: the size of the largest connected component of immunized network and the number of infected nodes. Simulation results demonstrate that the proposed strategies based on two rounds of sorting are effective for heterogeneous networks and their immunization effects are better than that of the degree immunizations.

  2. WFIRST: Exoplanet Target Selection and Scheduling with Greedy Optimization

    Science.gov (United States)

    Keithly, Dean; Garrett, Daniel; Delacroix, Christian; Savransky, Dmitry

    2018-01-01

    We present target selection and scheduling algorithms for missions with direct imaging of exoplanets, and the Wide Field Infrared Survey Telescope (WFIRST) in particular, which will be equipped with a coronagraphic instrument (CGI). Optimal scheduling of CGI targets can maximize the expected value of directly imaged exoplanets (completeness). Using target completeness as a reward metric and integration time plus overhead time as a cost metric, we can maximize the sum completeness for a mission with a fixed duration. We optimize over these metrics to create a list of target stars using a greedy optimization algorithm based off altruistic yield optimization (AYO) under ideal conditions. We simulate full missions using EXOSIMS by observing targets in this list for their predetermined integration times. In this poster, we report the theoretical maximum sum completeness, mean number of detected exoplanets from Monte Carlo simulations, and the ideal expected value of the simulated missions.

  3. Deep Brain Stimulation Target Selection for Parkinson's Disease.

    Science.gov (United States)

    Honey, Christopher R; Hamani, Clement; Kalia, Suneil K; Sankar, Tejas; Picillo, Marina; Munhoz, Renato P; Fasano, Alfonso; Panisset, Michel

    2017-01-01

    During the "DBS Canada Day" symposium held in Toronto July 4-5, 2014, the scientific committee invited experts to discuss three main questions on target selection for deep brain stimulation (DBS) of patients with Parkinson's disease (PD). First, is the subthalamic nucleus (STN) or the globus pallidus internus (GPi) the ideal target? In summary, both targets are equally effective in improving the motor symptoms of PD. STN allows a greater medications reduction, while GPi exerts a direct antidyskinetic effect. Second, are there further potential targets? Ventral intermediate nucleus DBS has significant long-term benefit for tremor control but insufficiently addresses other motor features of PD. DBS in the posterior subthalamic area also reduces tremor. The pedunculopontine nucleus remains an investigational target. Third, should DBS for PD be performed unilaterally, bilaterally or staged? Unilateral STN DBS can be proposed to asymmetric patients. There is no evidence that a staged bilateral approach reduces the incidence of DBS-related adverse events.

  4. Automatic smoothing parameter selection in GAMLSS with an application to centile estimation.

    Science.gov (United States)

    Rigby, Robert A; Stasinopoulos, Dimitrios M

    2014-08-01

    A method for automatic selection of the smoothing parameters in a generalised additive model for location, scale and shape (GAMLSS) model is introduced. The method uses a P-spline representation of the smoothing terms to express them as random effect terms with an internal (or local) maximum likelihood estimation on the predictor scale of each distribution parameter to estimate its smoothing parameters. This provides a fast method for estimating multiple smoothing parameters. The method is applied to centile estimation where all four parameters of a distribution for the response variable are modelled as smooth functions of a transformed explanatory variable x This allows smooth modelling of the location, scale, skewness and kurtosis parameters of the response variable distribution as functions of x. © The Author(s) 2013 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav.

  5. Neural Networks for Target Selection in Direct Marketing

    NARCIS (Netherlands)

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

    2001-01-01

    textabstractPartly due to a growing interest in direct marketing, it has become an important application field for data mining. Many techniques have been applied to select the targets in commercial applications, such as statistical regression, regression trees, neural computing, fuzzy clustering

  6. 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

  7. Targeted Diazotransfer Reagents Enable Selective Modification of Proteins with Azides.

    Science.gov (United States)

    Lohse, Jonas; Swier, Lotteke J Y M; Oudshoorn, Ruben C; Médard, Guillaume; Kuster, Bernhard; Slotboom, Dirk-Jan; Witte, Martin D

    2017-04-19

    In chemical biology, azides are used to chemically manipulate target structures in a bioorthogonal manner for a plethora of applications ranging from target identification to the synthesis of homogeneously modified protein conjugates. While a variety of methods have been established to introduce the azido group into recombinant proteins, a method that directly converts specific amino groups in endogenous proteins is lacking. Here, we report the first biotin-tethered diazotransfer reagent DtBio and demonstrate that it selectively modifies the model proteins streptavidin and avidin and the membrane protein BioY on cell surface. The reagent converts amines in the proximity of the binding pocket to azides and leaves the remaining amino groups in streptavidin untouched. Reagents of this novel class will find use in target identification as well as the selective functionalization and bioorthogonal protection of proteins.

  8. Target Selection for the SDSS-IV APOGEE-2 Survey

    Energy Technology Data Exchange (ETDEWEB)

    Zasowski, G. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Cohen, R. E.; Carlberg, J. K.; Fleming, Scott W. [Space Telescope Science Institute, Baltimore, MD 21218 (United States); Chojnowski, S. D.; Holtzman, J. [Department of Astronomy, New Mexico State University, Las Cruces, NM 88001 (United States); Santana, F. [Departamento de Astronomía, Universidad de Chile, Santiago (Chile); Oelkers, R. J.; Bird, J. C. [Department of Physics and Astronomy, Vanderbilt University, Nashville, TN 37235 (United States); Andrews, B. [PITT PACC, Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Beaton, R. L. [The Observatories of the Carnegie Institution for Science, Pasadena, CA 91101 (United States); Bender, C.; Cunha, K. [Steward Observatory, The University of Arizona, Tucson, AZ 85719 (United States); Bovy, J. [Department of Astronomy and Astrophysics and Dunlap Institute for Astronomy and Astrophysics, University of Toronto, Toronto, ON M5S 3H4 (Canada); Covey, K. [Department of Physics and Astronomy, Western Washington University, Bellingham, WA 98225 (United States); Dell’Agli, F.; García-Hernández, D. A. [Departamento de Astrofísica, Universidad de La Laguna, and Instituto de Astrofísica de Canarias, La Laguna, Tenerife (Spain); Frinchaboy, P. M. [Department of Physics and Astronomy, Texas Christian University, Fort Worth, TX 76129 (United States); Harding, P. [Department of Astronomy, Case Western Reserve University, Cleveland, OH 44106 (United States); Johnson, J. A., E-mail: gail.zasowski@gmail.com [Department of Astronomy, The Ohio State University, Columbus, OH 43210 (United States); and others

    2017-11-01

    APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ∼3 × 10{sup 5} stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding on APOGEE’s goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.

  9. Predicting selective drug targets in cancer through metabolic networks

    Science.gov (United States)

    Folger, Ori; Jerby, Livnat; Frezza, Christian; Gottlieb, Eyal; Ruppin, Eytan; Shlomi, Tomer

    2011-01-01

    The interest in studying metabolic alterations in cancer and their potential role as novel targets for therapy has been rejuvenated in recent years. Here, we report the development of the first genome-scale network model of cancer metabolism, validated by correctly identifying genes essential for cellular proliferation in cancer cell lines. The model predicts 52 cytostatic drug targets, of which 40% are targeted by known, approved or experimental anticancer drugs, and the rest are new. It further predicts combinations of synthetic lethal drug targets, whose synergy is validated using available drug efficacy and gene expression measurements across the NCI-60 cancer cell line collection. Finally, potential selective treatments for specific cancers that depend on cancer type-specific downregulation of gene expression and somatic mutations are compiled. PMID:21694718

  10. Target Selection for the SDSS-IV APOGEE-2 Survey

    Science.gov (United States)

    Zasowski, G.; Cohen, R. E.; Chojnowski, S. D.; Santana, F.; Oelkers, R. J.; Andrews, B.; Beaton, R. L.; Bender, C.; Bird, J. C.; Bovy, J.; Carlberg, J. K.; Covey, K.; Cunha, K.; Dell'Agli, F.; Fleming, Scott W.; Frinchaboy, P. M.; García-Hernández, D. A.; Harding, P.; Holtzman, J.; Johnson, J. A.; Kollmeier, J. A.; Majewski, S. R.; Mészáros, Sz.; Munn, J.; Muñoz, R. R.; Ness, M. K.; Nidever, D. L.; Poleski, R.; Román-Zúñiga, C.; Shetrone, M.; Simon, J. D.; Smith, V. V.; Sobeck, J. S.; Stringfellow, G. S.; Szigetiáros, L.; Tayar, J.; Troup, N.

    2017-11-01

    APOGEE-2 is a high-resolution, near-infrared spectroscopic survey observing ˜3 × 105 stars across the entire sky. It is the successor to APOGEE and is part of the Sloan Digital Sky Survey IV (SDSS-IV). APOGEE-2 is expanding on APOGEE’s goals of addressing critical questions of stellar astrophysics, stellar populations, and Galactic chemodynamical evolution using (1) an enhanced set of target types and (2) a second spectrograph at Las Campanas Observatory in Chile. APOGEE-2 is targeting red giant branch and red clump stars, RR Lyrae, low-mass dwarf stars, young stellar objects, and numerous other Milky Way and Local Group sources across the entire sky from both hemispheres. In this paper, we describe the APOGEE-2 observational design, target selection catalogs and algorithms, and the targeting-related documentation included in the SDSS data releases.

  11. Iterative reconstruction and automatic tube voltage selection reduce clinical CT radiation doses and image noise.

    Science.gov (United States)

    O'Hora, L; Foley, S J

    2018-02-01

    Computed Tomography (CT) use has increased in recent years with trends indicating increasing population doses as a result. Optimization of clinical radiation doses through technological developments has demonstrated potential to reduce patient dose from CT. This study aimed to quantify these dose reductions across a large clinical cohort. Patient cohort was divided into three groups, assigned by CT optimisation technique. Group one underwent scanning with automated tube current modulation only. Group two underwent scanning with automated tube current modulation and iterative reconstruction and group three underwent scanning with automated tube current modulation, iterative reconstruction and automatic tube voltage modulation. Patient dose length product doses were retrospectively collected for the three groups. Clinical radiation doses between the groups were compared for four common CT examinations (Brain, pulmonary angiography, abdomen and thorax abdomen pelvis scans). Of 4011 patients, group one comprised of 1643 patients (40.96%), group two 1077 patients (26.85%) and group three 1291 patients (32.19%). No differences were found when comparing AP diameter between groups (p ≥ 0.05). Statistically significant dose reductions of 16-31% were achieved using iterative reconstruction alone (p = 0.001) and 24-42% with both iterative reconstruction and automatic tube voltage selection (p = 0.001). Objective noise improved when iterative reconstruction was used (p staff and procedural protocols remaining consistent throughout. Dose reductions are likely to reflect the clinical dose reducing potential of the optimization software investigated. Copyright © 2017 The College of Radiographers. Published by Elsevier Ltd. All rights reserved.

  12. AUTOMATIC TRAINING SITE SELECTION FOR AGRICULTURAL CROP CLASSIFICATION: A CASE STUDY ON KARACABEY PLAIN, TURKEY

    Directory of Open Access Journals (Sweden)

    A. Ozdarici Ok

    2012-09-01

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

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

    Science.gov (United States)

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

    2015-01-01

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

  14. Semi-Automatic Selection of Ground Control Points for High Resolution Remote Sensing Data in Urban Areas

    Directory of Open Access Journals (Sweden)

    Gulbe Linda

    2016-12-01

    Full Text Available Geometrical accuracy of remote sensing data often is ensured by geometrical transforms based on Ground Control Points (GCPs. Manual selection of GCP is a time-consuming process, which requires some sort of automation. Therefore, the aim of this study is to present and evaluate methodology for easier, semi-automatic selection of ground control points for urban areas. Custom line scanning algorithm was implemented and applied to data in order to extract potential GCPs for an image analyst. The proposed method was tested for classical orthorectification and special object polygon transform. Results are convincing and show that in the test case semi-automatic methodology is able to correct locations of 70 % (thermal data – 80 % (orthophoto images of buildings. Geometrical transform for subimages of approximately 3 hectares with approximately 12 automatically found GCPs resulted in RSME approximately 1 meter with standard deviation of 1.2 meters.

  15. Target Selection for the SDSS-III MARVELS Survey

    Science.gov (United States)

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

    2015-06-01

    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 ∼ 11,000) 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 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 ∼30% for the first phase of the MARVELS survey. Thereafter, the survey instead applied a reduced proper motion cut to eliminate giants and used the Infrared Flux Method to estimate effective temperatures, using only extant photmetric and proper-motion catalog information. The target selection method introduced here may be useful for other surveys that need to rely on extant catalog data for selection of specific stellar populations.

  16. Advances in image compression and automatic target recognition; Proceedings of the Meeting, Orlando, FL, Mar. 30, 31, 1989

    Science.gov (United States)

    Tescher, Andrew G. (Editor)

    1989-01-01

    Various papers on image compression and automatic target recognition are presented. Individual topics addressed include: target cluster detection in cluttered SAR imagery, model-based target recognition using laser radar imagery, Smart Sensor front-end processor for feature extraction of images, object attitude estimation and tracking from a single video sensor, symmetry detection in human vision, analysis of high resolution aerial images for object detection, obscured object recognition for an ATR application, neural networks for adaptive shape tracking, statistical mechanics and pattern recognition, detection of cylinders in aerial range images, moving object tracking using local windows, new transform method for image data compression, quad-tree product vector quantization of images, predictive trellis encoding of imagery, reduced generalized chain code for contour description, compact architecture for a real-time vision system, use of human visibility functions in segmentation coding, color texture analysis and synthesis using Gibbs random fields.

  17. Target selection and deselection at the Berkeley Structural Genomics Center.

    Science.gov (United States)

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

    2006-02-01

    At the Berkeley Structural Genomics Center (BSGC), our goal is to obtain a near-complete structural complement of proteins in the minimal organisms Mycoplasma genitalium and M. pneumoniae, two closely related pathogens. Current targets for structure determination have been selected in six major stages, starting with those predicted to be most tractable to high throughput study and likely to yield new structural information. We report on the process used to select these proteins, as well as our target deselection procedure. Target deselection reduces experimental effort by eliminating targets similar to those recently solved by the structural biology community or other centers. We measure the impact of the 69 structures solved at the BSGC as of July 2004 on structure prediction coverage of the M. pneumoniae and M. genitalium proteomes. The number of Mycoplasma proteins for which the fold could first be reliably assigned based on structures solved at the BSGC (24 M. pneumoniae and 21 M. genitalium) is approximately 25% of the total resulting from work at all structural genomics centers and the worldwide structural biology community (94 M. pneumoniae and 86 M. genitalium) during the same period. As the number of structures contributed by the BSGC during that period is less than 1% of the total worldwide output, the benefits of a focused target selection strategy are apparent. If the structures of all current targets were solved, the percentage of M. pneumoniae proteins for which folds could be reliably assigned would increase from approximately 57% (391 of 687) at present to around 80% (550 of 687), and the percentage of the proteome that could be accurately modeled would increase from around 37% (254 of 687) to about 64% (438 of 687). In M. genitalium, the percentage of the proteome that could be structurally annotated based on structures of our remaining targets would rise from 72% (348 of 486) to around 76% (371 of 486), with the percentage of accurately modeled

  18. The performance of an automatic acoustic-based program classifier compared to hearing aid users' manual selection of listening programs.

    Science.gov (United States)

    Searchfield, Grant D; Linford, Tania; Kobayashi, Kei; Crowhen, David; Latzel, Matthias

    2018-03-01

    To compare preference for and performance of manually selected programmes to an automatic sound classifier, the Phonak AutoSense OS. A single blind repeated measures study. Participants were fit with Phonak Virto V90 ITE aids; preferences for different listening programmes were compared across four different sound scenarios (speech in: quiet, noise, loud noise and a car). Following a 4-week trial preferences were reassessed and the users preferred programme was compared to the automatic classifier for sound quality and hearing in noise (HINT test) using a 12 loudspeaker array. Twenty-five participants with symmetrical moderate-severe sensorineural hearing loss. Participant preferences of manual programme for scenarios varied considerably between and within sessions. A HINT Speech Reception Threshold (SRT) advantage was observed for the automatic classifier over participant's manual selection for speech in quiet, loud noise and car noise. Sound quality ratings were similar for both manual and automatic selections. The use of a sound classifier is a viable alternative to manual programme selection.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2009-07-01

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

  20. Nanostructured materials for selective recognition and targeted drug delivery

    International Nuclear Information System (INIS)

    Kotrotsiou, O; Kotti, K; Dini, E; Kammona, O; Kiparissides, C

    2005-01-01

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

  1. Think Outside The Color Box: Probabilistic Target Selection And The SDSS-XDQSO Quasar Targeting Catalog

    International Nuclear Information System (INIS)

    Bovy, J.; Sheldon, E.; Hennawi, J.F.; Hogg, D.W.; Myers, A.D.

    2011-01-01

    We present the SDSS-XDQSO quasar targeting catalog for efficient flux-based quasar target selection down to the faint limit of the Sloan Digital Sky Survey (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 outperforms all other flux-based methods for selecting the medium-redshift quasars of our primary interest. We make code to reproduce the XDQSO quasar target selection publicly available.

  2. Selective visual working memory in fear of spiders: The role of automaticity and material-specificity

    NARCIS (Netherlands)

    Reinecke, A.; Becker, E.S.; Rinck, M.

    2009-01-01

    Following cognitive models of anxiety, biases occur if threat processing is automatic versus strategic. Therefore, most of these models predict attentional bias, but not explicit memory bias. We suggest dividing memory into the highly automatic working memory (WM) component versus long-term memory

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

    Science.gov (United States)

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

    2014-01-01

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

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

    Science.gov (United States)

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

    2014-09-16

    Recent psychophysical experiments have shown that working memory for visual surface features interacts with saccadic motor planning, even in tasks where the saccade target is unambiguously specified by spatial cues. Specifically, a match between a memorized color and the color of either the designated target or a distractor stimulus influences saccade target selection, saccade amplitudes, and latencies in a systematic fashion. To elucidate these effects, we present a dynamic neural field model in combination with new experimental data. The model captures the neural processes underlying visual perception, working memory, and saccade planning relevant to the psychophysical experiment. It consists of a low-level visual sensory representation that interacts with two separate pathways: a spatial pathway implementing spatial attention and saccade generation, and a surface feature pathway implementing color working memory and feature attention. Due to bidirectional coupling between visual working memory and feature attention in the model, the working memory content can indirectly exert an effect on perceptual processing in the low-level sensory representation. This in turn biases saccadic movement planning in the spatial pathway, allowing the model to quantitatively reproduce the observed interaction effects. The continuous coupling between representations in the model also implies that modulation should be bidirectional, and model simulations provide specific predictions for complementary effects of saccade target selection on visual working memory. These predictions were empirically confirmed in a new experiment: Memory for a sample color was biased toward the color of a task-irrelevant saccade target object, demonstrating the bidirectional coupling between visual working memory and perceptual processing. © 2014 ARVO.

  5. Automatic optimal input command for linearization of cMUT output by a temporal target.

    Science.gov (United States)

    Ménigot, Sébastien; Certon, Dominique; Gross, Dominique; Girault, Jean-Marc

    2014-10-01

    Capacitive micromachined ultrasonic transducers (cMUTs) are a promising alternative to the piezoelectric transducer. However, their native nonlinear behavior is a limitation for their use in medical ultrasound applications. Several methods based on the pre-compensation of a preselected input voltage have been proposed to cancel out the harmonic components generated. Unfortunately, these existing pre-compensation methods have two major flaws. The first is that the pre-compensation procedure is not generally automatic, and the second is that they can only reduce the second harmonic component. This can, therefore, limit their use for some imaging methods, which require a broader bandwidth, e.g., to receive the third harmonic component. In this study, we generalized the presetting methods to reduce all nonlinearities in the cMUT output. Our automatic pre-compensation method can work whatever the excitation waveform. The precompensation method is based on the nonlinear modeling of harmonic components from a Volterra decomposition in which the parameters are evaluated by using a Nelder-Mead algorithm. To validate the feasibility of this approach, the method was applied to an element of a linear array with several types of excitation often encountered in encoded ultrasound imaging. The results showed that the nonlinear components were reduced by up to 21.2 dB.

  6. 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.)

  7. SELECTION, PRIORITIZATION, AND CHARACTERISTICS OF KEPLER TARGET STARS

    International Nuclear Information System (INIS)

    Batalha, Natalie M.; Borucki, William J.; Koch, David G.; Bryson, Stephen T.; Haas, Michael R.; Brown, Timothy M.; Caldwell, Douglas A.; Hall, Jennifer R.; Gilliland, Ronald L.; Latham, David W.; Meibom, Soren; Monet, David G.

    2010-01-01

    The Kepler Mission began its 3.5 year photometric monitoring campaign in 2009 May on a select group of approximately 150,000 stars. The stars were chosen from the ∼ half million in the field of view that are brighter than 16th magnitude. The selection criteria are quantitative metrics designed to optimize the scientific yield of the mission with regard to the detection of Earth-size planets in the habitable zone. This yields more than 90,000 G-type stars on or close to the main sequence, >20, 000 of which are brighter than 14th magnitude. At the temperature extremes, the sample includes approximately 3000 M-type dwarfs and a small sample of O- and B-type MS stars (<200). The small numbers of giants are included in the sample: ∼5000 stars with surface gravities log(g) < 3.5. We present a brief summary of the selection process and the stellar populations it yields in terms of surface gravity, effective temperature, and apparent magnitude. In addition to the primary, statistically derived target set, several ancillary target lists were manually generated to enhance the science of the mission, examples being: known eclipsing binaries, open cluster members, and high proper motion stars.

  8. Selective inhibition of retinal angiogenesis by targeting PI3 kinase.

    Directory of Open Access Journals (Sweden)

    Yolanda Alvarez

    Full Text Available Ocular neovascularisation is a pathological hallmark of some forms of debilitating blindness including diabetic retinopathy, age related macular degeneration and retinopathy of prematurity. Current therapies for delaying unwanted ocular angiogenesis include laser surgery or molecular inhibition of the pro-angiogenic factor VEGF. However, targeting of angiogenic pathways other than, or in combination to VEGF, may lead to more effective and safer inhibitors of intraocular angiogenesis. In a small chemical screen using zebrafish, we identify LY294002 as an effective and selective inhibitor of both developmental and ectopic hyaloid angiogenesis in the eye. LY294002, a PI3 kinase inhibitor, exerts its anti-angiogenic effect in a dose-dependent manner, without perturbing existing vessels. Significantly, LY294002 delivered by intraocular injection, significantly inhibits ocular angiogenesis without systemic side-effects and without diminishing visual function. Thus, targeting of PI3 kinase pathways has the potential to effectively and safely treat neovascularisation in eye disease.

  9. Coherent digital/optical system for automatic target recognition (Abstract Only)

    Science.gov (United States)

    Derr, John I.; Ghaffari, Tammy G.

    1991-04-01

    Litton Data Systems has developed a hybrid ATR system using DataCube signal processing and imaging boards controlled by a host Sun workstation. The input image preprocessor includes detection algorithms that locate candidate targets in a simulated or real JR scene and segmentation algorithms that generate target outlines which are normalized for recognition processing by Litton's LIGHTMOD optical correlator. Target detection performs a raster scan over the image using nested boxes to find detection pixels based on intesity/variance contrasts. Segmentation operates on windows centered at the centroids of connected components of detection pixels. Optimal thresholds are determined from gray scale histograms. Multimodal optimization seeks to maximize edge/boundary proximities for candidate target and island components obtained by thresholding with respect to the optimal thresholds. Relaxation smooths the boundaries of optimal target components or merged target/island components. Normalization algorithms scale and center the component boundaries in a 128x128 LIGHT-MOD window. The LIGHT_MOD correlates the FT of the normalized outline with the FTs of a reference library of target outlines. Template matching is the basic technique used for recognition.

  10. Supervised non-negative tensor factorization for automatic hyperspectral feature extraction and target discrimination

    Science.gov (United States)

    Anderson, Dylan; Bapst, Aleksander; Coon, Joshua; Pung, Aaron; Kudenov, Michael

    2017-05-01

    Hyperspectral imaging provides a highly discriminative and powerful signature for target detection and discrimination. Recent literature has shown that considering additional target characteristics, such as spatial or temporal profiles, simultaneously with spectral content can greatly increase classifier performance. Considering these additional characteristics in a traditional discriminative algorithm requires a feature extraction step be performed first. An example of such a pipeline is computing a filter bank response to extract spatial features followed by a support vector machine (SVM) to discriminate between targets. This decoupling between feature extraction and target discrimination yields features that are suboptimal for discrimination, reducing performance. This performance reduction is especially pronounced when the number of features or available data is limited. In this paper, we propose the use of Supervised Nonnegative Tensor Factorization (SNTF) to jointly perform feature extraction and target discrimination over hyperspectral data products. SNTF learns a tensor factorization and a classification boundary from labeled training data simultaneously. This ensures that the features learned via tensor factorization are optimal for both summarizing the input data and separating the targets of interest. Practical considerations for applying SNTF to hyperspectral data are presented, and results from this framework are compared to decoupled feature extraction/target discrimination pipelines.

  11. 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.

  12. An assessment of spacecraft target mode selection methods

    Science.gov (United States)

    Mercer, J. F.; Aglietti, G. S.; Remedia, M.; Kiley, A.

    2017-11-01

    Coupled Loads Analyses (CLAs), using finite element models (FEMs) of the spacecraft and launch vehicle to simulate critical flight events, are performed in order to determine the dynamic loadings that will be experienced by spacecraft during launch. A validation process is carried out on the spacecraft FEM beforehand to ensure that the dynamics of the analytical model sufficiently represent the behavior of the physical hardware. One aspect of concern is the containment of the FEM correlation and update effort to focus on the vibration modes which are most likely to be excited under test and CLA conditions. This study therefore provides new insight into the prioritization of spacecraft FEM modes for correlation to base-shake vibration test data. The work involved example application to large, unique, scientific spacecraft, with modern FEMs comprising over a million degrees of freedom. This comprehensive investigation explores: the modes inherently important to the spacecraft structures, irrespective of excitation; the particular 'critical modes' which produce peak responses to CLA level excitation; an assessment of several traditional target mode selection methods in terms of ability to predict these 'critical modes'; and an indication of the level of correlation these FEM modes achieve compared to corresponding test data. Findings indicate that, although the traditional methods of target mode selection have merit and are able to identify many of the modes of significance to the spacecraft, there are 'critical modes' which may be missed by conventional application of these methods. The use of different thresholds to select potential target modes from these parameters would enable identification of many of these missed modes. Ultimately, some consideration of the expected excitations is required to predict all modes likely to contribute to the response of the spacecraft in operation.

  13. 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.

  14. Automatic Target Recognition for Hyperspectral Imagery Using High-Order Statistics

    National Research Council Canada - National Science Library

    Ren, Hsuan; Du, Qian; Wang, Jing; Chang, Chein-I; Jensen, James O; Jensen, Janet L

    2006-01-01

    Due to recent advances in hyperspectral imaging sensors many subtle unknown signal sources that cannot be resolved by multispectral sensors can be now uncovered for target detection, discrimination, and identification...

  15. 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...... to maintaining phenotypic variation in natural populations. Nevertheless, its prevalence and specific targets in the human genome remain largely unknown. We have analyzed the patterns of diversity and divergence of 13,400 genes in two human populations using an unbiased single-nucleotide polymorphism data set......, a genome-wide approach, and a method that incorporates demography in neutrality tests. We identified an unbiased catalog of genes with signatures of long-term balancing selection, which includes immunity genes as well as genes encoding keratins and membrane channels; the catalog also shows enrichment...

  16. 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

  17. Selective Targeting to Glioma with Nucleic Acid Aptamers.

    Directory of Open Access Journals (Sweden)

    Shraddha Aptekar

    Full Text Available Malignant glioma is characterised by a rapid growth rate and high capacity for invasive infiltration to surrounding brain tissue; hence, diagnosis and treatment is difficult and patient survival is poor. Aptamers contribute a promising and unique technology for the in vitro imaging of live cells and tissues, with a potentially bright future in clinical diagnostics and therapeutics for malignant glioma. The binding selectivity, uptake capacity and binding target of two DNA aptamers, SA43 and SA44, were investigated in glioma cells and patient tissues. The binding assay showed that SA43 and SA44 bound with strong affinity (Kd, 21.56 ± 4.60 nM and Kd, 21.11 ± 3.30 nM respectively to the target U87MG cells. Quantitative analysis by flow cytometry showed that the aptamers were able to actively internalise in U87MG and 1321N1 glioma cells compared to the non-cancerous and non-glioma cell types. Confocal microscopy confirmed staining in the cytoplasm, and co-localisation studies with endoplasmic reticulum, Golgi apparatus and lysosomal markers suggested internalisation and compartmentalisation within the endomembrane system. Both aptamers selectively bound to Ku 70 and Ku 80 DNA repair proteins as determined by aptoprecipitation (AP followed by mass spectrometry analysis and confirmation by Western blot. In addition, aptohistochemical (AHC staining on paraffin embedded, formalin fixed patient tissues revealed that the binding selectivity was significantly higher for SA43 aptamer in glioma tissues (grade I, II, III and IV compared to the non-cancerous tissues, whereas SA44 did not show selectivity towards glioma tissues. The results indicate that SA43 aptamer can differentiate between glioma and non-cancerous cells and tissues and therefore, shows promise for histological diagnosis of glioma.

  18. 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.)

  19. 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.

  20. Attentional set mixing: Effects on target selection and selective response activation.

    Science.gov (United States)

    Ruge, Hannes; Stoet, Gijsbert; Naumann, Ewald

    2006-07-01

    Performance is impaired under set mixing conditions that require frequent readjustments of attentional focus over an extended time period. We compared set repetitions within pure blocks (constant focus of attention) to physically identical repetitions within mixed blocks (changing focus of attention). The aim was to investigate how set mixing affects target selection, indexed by the N2pc component, and selective response activation, indexed by the lateralized readiness potential (LRP). We found that set mixing prolonged the evolution of the N2pc while leaving its onset unaffected. Impaired target selection indicated by the N2pc mixing effect also delayed the start of response planning indexed by an onset delay of the stimulus-locked LRP, explaining one part of the behavioral mixing cost. A larger part of mixing cost could be attributed to a prolonged response planning phase, indexed by an earlier onset of the response-locked LRP.

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

    International Nuclear Information System (INIS)

    Mutanga, Theodore F.; Boer, Hans C.J. de; Wielen, Gerard J. van der; Wentzler, Davy; Barnhoorn, Jaco; Incrocci, Luca; Heijmen, Ben J.M.

    2008-01-01

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

  2. Automatic detection of the unknown number point targets in FMICW radar signals

    Czech Academy of Sciences Publication Activity Database

    Rejfek, L.; Mošna, Zbyšek; Beran, L.; Fišer, O.; Dobrovolný, M.

    2017-01-01

    Roč. 4, č. 11 (2017), s. 116-120 ISSN 2313-626X R&D Projects: GA ČR(CZ) GA15-24688S Institutional support: RVO:68378289 Keywords : FMICW radar * 2D FFT * signal filtration * taraget detection * target parameter estimation Subject RIV: DG - Athmosphere Sciences, Meteorology OBOR OECD: Meteorology and atmospheric sciences http://science-gate.com/IJAAS/ Articles /2017-4-11/18%202017-4-11-pp.116-120.pdf

  3. Do the Contents of Visual Working Memory Automatically Influence Attentional Selection during Visual Search?

    Science.gov (United States)

    Woodman, Geoffrey F.; Luck, Steven J.

    2007-01-01

    In many theories of cognition, researchers propose that working memory and perception operate interactively. For example, in previous studies researchers have suggested that sensory inputs matching the contents of working memory will have an automatic advantage in the competition for processing resources. The authors tested this hypothesis by…

  4. Fixture Design with FIXES: the Automatic Selection of Positioning, Clamping and Support Features for Prismatic Parts

    NARCIS (Netherlands)

    Boerma, J.R.; Kals, H.J.J.

    1989-01-01

    FIXES is a computer aided system for the automatic generation of set-ups and for fixture design for prismatic parts, to be used in an integrated process planning environment. The generation of set-ups having been described in a previous paper [9], this paper concentrates on fixture design, in

  5. Automatic selection of localized region-based active contour models using image content analysis applied to brain tumor segmentation.

    Science.gov (United States)

    Ilunga-Mbuyamba, Elisee; Avina-Cervantes, Juan Gabriel; Cepeda-Negrete, Jonathan; Ibarra-Manzano, Mario Alberto; Chalopin, Claire

    2017-12-01

    Brain tumor segmentation is a routine process in a clinical setting and provides useful information for diagnosis and treatment planning. Manual segmentation, performed by physicians or radiologists, is a time-consuming task due to the large quantity of medical data generated presently. Hence, automatic segmentation methods are needed, and several approaches have been introduced in recent years including the Localized Region-based Active Contour Model (LRACM). There are many popular LRACM, but each of them presents strong and weak points. In this paper, the automatic selection of LRACM based on image content and its application on brain tumor segmentation is presented. Thereby, a framework to select one of three LRACM, i.e., Local Gaussian Distribution Fitting (LGDF), localized Chan-Vese (C-V) and Localized Active Contour Model with Background Intensity Compensation (LACM-BIC), is proposed. Twelve visual features are extracted to properly select the method that may process a given input image. The system is based on a supervised approach. Applied specifically to Magnetic Resonance Imaging (MRI) images, the experiments showed that the proposed system is able to correctly select the suitable LRACM to handle a specific image. Consequently, the selection framework achieves better accuracy performance than the three LRACM separately. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. 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.

  7. MESSI: metabolic engineering target selection and best strain identification tool.

    Science.gov (United States)

    Kang, Kang; Li, Jun; Lim, Boon Leong; Panagiotou, Gianni

    2015-01-01

    Metabolic engineering and synthetic biology are synergistically related fields for manipulating target pathways and designing microorganisms that can act as chemical factories. Saccharomyces cerevisiae's ideal bioprocessing traits make yeast a very attractive chemical factory for production of fuels, pharmaceuticals, nutraceuticals as well as a wide range of chemicals. However, future attempts of engineering S. cerevisiae's metabolism using synthetic biology need to move towards more integrative models that incorporate the high connectivity of metabolic pathways and regulatory processes and the interactions in genetic elements across those pathways and processes. To contribute in this direction, we have developed Metabolic Engineering target Selection and best Strain Identification tool (MESSI), a web server for predicting efficient chassis and regulatory components for yeast bio-based production. The server provides an integrative platform for users to analyse ready-to-use public high-throughput metabolomic data, which are transformed to metabolic pathway activities for identifying the most efficient S. cerevisiae strain for the production of a compound of interest. As input MESSI accepts metabolite KEGG IDs or pathway names. MESSI outputs a ranked list of S. cerevisiae strains based on aggregation algorithms. Furthermore, through a genome-wide association study of the metabolic pathway activities with the strains' natural variation, MESSI prioritizes genes and small variants as potential regulatory points and promising metabolic engineering targets. Users can choose various parameters in the whole process such as (i) weight and expectation of each metabolic pathway activity in the final ranking of the strains, (ii) Weighted AddScore Fuse or Weighted Borda Fuse aggregation algorithm, (iii) type of variants to be included, (iv) variant sets in different biological levels.Database URL: http://sbb.hku.hk/MESSI/. © The Author(s) 2015. Published by Oxford University

  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. Automatic target recognition using a feature-based optical neural network

    Science.gov (United States)

    Chao, Tien-Hsin

    1992-01-01

    An optical neural network based upon the Neocognitron paradigm (K. Fukushima et al. 1983) is introduced. A novel aspect of the architectural design is shift-invariant multichannel Fourier optical correlation within each processing layer. Multilayer processing is achieved by iteratively feeding back the output of the feature correlator to the input spatial light modulator and updating the Fourier filters. By training the neural net with characteristic features extracted from the target images, successful pattern recognition with intra-class fault tolerance and inter-class discrimination is achieved. A detailed system description is provided. Experimental demonstration of a two-layer neural network for space objects discrimination is also presented.

  10. A Clonal Selection Algorithm for Minimizing Distance Travel and Back Tracking of Automatic Guided Vehicles in Flexible Manufacturing System

    Science.gov (United States)

    Chawla, Viveak Kumar; Chanda, Arindam Kumar; Angra, Surjit

    2018-03-01

    The flexible manufacturing system (FMS) constitute of several programmable production work centers, material handling systems (MHSs), assembly stations and automatic storage and retrieval systems. In FMS, the automatic guided vehicles (AGVs) play a vital role in material handling operations and enhance the performance of the FMS in its overall operations. To achieve low makespan and high throughput yield in the FMS operations, it is highly imperative to integrate the production work centers schedules with the AGVs schedules. The Production schedule for work centers is generated by application of the Giffler and Thompson algorithm under four kind of priority hybrid dispatching rules. Then the clonal selection algorithm (CSA) is applied for the simultaneous scheduling to reduce backtracking as well as distance travel of AGVs within the FMS facility. The proposed procedure is computationally tested on the benchmark FMS configuration from the literature and findings from the investigations clearly indicates that the CSA yields best results in comparison of other applied methods from the literature.

  11. Double Weight-Based SAR and Infrared Sensor Fusion for Automatic Ground Target Recognition with Deep Learning

    Directory of Open Access Journals (Sweden)

    Sungho Kim

    2018-01-01

    Full Text Available This paper presents a novel double weight-based synthetic aperture radar (SAR and infrared (IR sensor fusion method (DW-SIF for automatic ground target recognition (ATR. IR-based ATR can provide accurate recognition because of its high image resolution but it is affected by the weather conditions. On the other hand, SAR-based ATR shows a low recognition rate due to the noisy low resolution but can provide consistent performance regardless of the weather conditions. The fusion of an active sensor (SAR and a passive sensor (IR can lead to upgraded performance. This paper proposes a doubly weighted neural network fusion scheme at the decision level. The first weight ( α can measure the offline sensor confidence per target category based on the classification rate for an evaluation set. The second weight ( β can measure the online sensor reliability based on the score distribution for a test target image. The LeNet architecture-based deep convolution network (14 layers is used as an individual classifier. Doubly weighted sensor scores are fused by two types of fusion schemes, such as the sum-based linear fusion scheme ( α β -sum and neural network-based nonlinear fusion scheme ( α β -NN. The experimental results confirmed the proposed linear fusion method ( α β -sum to have the best performance among the linear fusion schemes available (SAR-CNN, IR-CNN, α -sum, β -sum, α β -sum, and Bayesian fusion. In addition, the proposed nonlinear fusion method ( α β -NN showed superior target recognition performance to linear fusion on the OKTAL-SE-based synthetic database.

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

    Science.gov (United States)

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

    2011-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Federico Andrea Santoni

    2010-11-01

    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.

  14. Automatic Localization of Target Vertebrae in Spine Surgery: Clinical Evaluation of the LevelCheck Registration Algorithm

    Science.gov (United States)

    Lo, Sheng-fu L.; Otake, Yoshito; Puvanesarajah, Varun; Wang, Adam S.; Uneri, Ali; De Silva, Tharindu; Vogt, Sebastian; Kleinszig, Gerhard; Elder, Benjamin D; Goodwin, C. Rory; Kosztowski, Thomas A.; Liauw, Jason A.; Groves, Mari; Bydon, Ali; Sciubba, Daniel M.; Witham, Timothy F.; Wolinsky, Jean-Paul; Aygun, Nafi; Gokaslan, Ziya L.; Siewerdsen, Jeffrey H.

    2015-01-01

    Study Design A 3D-2D image registration algorithm, “LevelCheck,” was used to automatically label vertebrae in intraoperative mobile radiographs obtained during spine surgery. Accuracy, computation time, and potential failure modes were evaluated in a retrospective study of 20 patients. Objective To measurethe performance of the LevelCheck algorithm using clinical images acquired during spine surgery. Summary of Background Data In spine surgery, the potential for wrong level surgery is significant due to the difficulty of localizing target vertebrae based solely on visual impression, palpation, and fluoroscopy. To remedy this difficulty and reduce the risk of wrong-level surgery, our team introduced a program (dubbed LevelCheck) to automatically localize target vertebrae in mobile radiographs using robust 3D-2D image registration to preoperative CT. Methods Twenty consecutive patients undergoing thoracolumbar spine surgery, for whom both a preoperative CT scan and an intraoperative mobile radiograph were available, were retrospectively analyzed. A board-certified neuroradiologist determined the “true” vertebra levels in each radiograph. Registration of the preoperative CT to the intraoperative radiographwere calculated via LevelCheck, and projection distance errors were analyzed. Five hundred random initializations were performed for eachpatient, andalgorithm settings (viz., the number of robust multi-starts, ranging 50 to 200) were varied to evaluate the tradeoff between registration error and computation time. Failure mode analysis was performed by individually analyzing unsuccessful registrations (>5 mm distance error) observed with 50 multi-starts. Results At 200 robust multi-starts (computation time of ∼26 seconds), the registration accuracy was 100% across all 10,000 trials. As the number of multi-starts (and computation time) decreased, the registration remained fairly robust, down to 99.3% registration accuracy at 50 multi-starts (computation time

  15. 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.

  16. Automatic target recognition and detection in infrared imagery under cluttered background

    Science.gov (United States)

    Gundogdu, Erhan; Koç, Aykut; Alatan, A. Aydın.

    2017-10-01

    Visual object classification has long been studied in visible spectrum by utilizing conventional cameras. Since the labeled images has recently increased in number, it is possible to train deep Convolutional Neural Networks (CNN) with significant amount of parameters. As the infrared (IR) sensor technology has been improved during the last two decades, labeled images extracted from IR sensors have been started to be used for object detection and recognition tasks. We address the problem of infrared object recognition and detection by exploiting 15K images from the real-field with long-wave and mid-wave IR sensors. For feature learning, a stacked denoising autoencoder is trained in this IR dataset. To recognize the objects, the trained stacked denoising autoencoder is fine-tuned according to the binary classification loss of the target object. Once the training is completed, the test samples are propagated over the network, and the probability of the test sample belonging to a class is computed. Moreover, the trained classifier is utilized in a detect-by-classification method, where the classification is performed in a set of candidate object boxes and the maximum confidence score in a particular location is accepted as the score of the detected object. To decrease the computational complexity, the detection step at every frame is avoided by running an efficient correlation filter based tracker. The detection part is performed when the tracker confidence is below a pre-defined threshold. The experiments conducted on the real field images demonstrate that the proposed detection and tracking framework presents satisfactory results for detecting tanks under cluttered background.

  17. Automatic feature selection for model-based reinforcement learning in factored MDPs

    NARCIS (Netherlands)

    Kroon, M.; Whiteson, S.; Wani, M.A.; Kantardzic, M.; Palade, V.; Kurgan, L.; Qi, A.

    2009-01-01

    Feature selection is an important challenge in machine learning. Unfortunately, most methods for automating feature selection are designed for supervised learning tasks and are thus either inapplicable or impractical for reinforcement learning. This paper presents a new approach to feature selection

  18. 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

  19. EFFECTIVELY SELECTING A TARGET POPULATION FOR A FUTURE COMPARATIVE STUDY.

    Science.gov (United States)

    Zhao, Lihui; Tian, Lu; Cai, Tianxi; Claggett, Brian; Wei, L J

    2013-01-01

    When comparing a new treatment with a control in a randomized clinical study, the treatment effect is generally assessed by evaluating a summary measure over a specific study population. The success of the trial heavily depends on the choice of such a population. In this paper, we show a systematic, effective way to identify a promising population, for which the new treatment is expected to have a desired benefit, utilizing the data from a current study involving similar comparator treatments. Specifically, using the existing data, we first create a parametric scoring system as a function of multiple multiple baseline covariates to estimate subject-specific treatment differences. Based on this scoring system, we specify a desired level of treatment difference and obtain a subgroup of patients, defined as those whose estimated scores exceed this threshold. An empirically calibrated threshold-specific treatment difference curve across a range of score values is constructed. The subpopulation of patients satisfying any given level of treatment benefit can then be identified accordingly. To avoid bias due to overoptimism, we utilize a cross-training-evaluation method for implementing the above two-step procedure. We then show how to select the best scoring system among all competing models. Furthermore, for cases in which only a single pre-specified working model is involved, inference procedures are proposed for the average treatment difference over a range of score values using the entire data set, and are justified theoretically and numerically. Lastly, the proposals are illustrated with the data from two clinical trials in treating HIV and cardiovascular diseases. Note that if we are not interested in designing a new study for comparing similar treatments, the new procedure can also be quite useful for the management of future patients, so that treatment may be targeted towards those who would receive nontrivial benefits to compensate for the risk or cost of the

  20. 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…

  1. Targeted Diazotransfer Reagents Enable Selective Modification of Proteins with Azides

    NARCIS (Netherlands)

    Lohse, Jonas; Swier, Lotteke; Oudshoorn, Ruben; Médard, Guillaume; Kuster, Bernhard; Slotboom, Dirk Jan; Witte, Martin D

    In chemical biology, azides are used to chemically manipulate target structures in a bioorthogonal manner for a plethora of applications ranging from target identification to the synthesis of homogeneously modified protein conjugates. While a variety of methods have been established to introduce the

  2. Automatic migraine classification via feature selection committee and machine learning techniques over imaging and questionnaire data.

    Science.gov (United States)

    Garcia-Chimeno, Yolanda; Garcia-Zapirain, Begonya; Gomez-Beldarrain, Marian; Fernandez-Ruanova, Begonya; Garcia-Monco, Juan Carlos

    2017-04-13

    Feature selection methods are commonly used to identify subsets of relevant features to facilitate the construction of models for classification, yet little is known about how feature selection methods perform in diffusion tensor images (DTIs). In this study, feature selection and machine learning classification methods were tested for the purpose of automating diagnosis of migraines using both DTIs and questionnaire answers related to emotion and cognition - factors that influence of pain perceptions. We select 52 adult subjects for the study divided into three groups: control group (15), subjects with sporadic migraine (19) and subjects with chronic migraine and medication overuse (18). These subjects underwent magnetic resonance with diffusion tensor to see white matter pathway integrity of the regions of interest involved in pain and emotion. The tests also gather data about pathology. The DTI images and test results were then introduced into feature selection algorithms (Gradient Tree Boosting, L1-based, Random Forest and Univariate) to reduce features of the first dataset and classification algorithms (SVM (Support Vector Machine), Boosting (Adaboost) and Naive Bayes) to perform a classification of migraine group. Moreover we implement a committee method to improve the classification accuracy based on feature selection algorithms. When classifying the migraine group, the greatest improvements in accuracy were made using the proposed committee-based feature selection method. Using this approach, the accuracy of classification into three types improved from 67 to 93% when using the Naive Bayes classifier, from 90 to 95% with the support vector machine classifier, 93 to 94% in boosting. The features that were determined to be most useful for classification included are related with the pain, analgesics and left uncinate brain (connected with the pain and emotions). The proposed feature selection committee method improved the performance of migraine diagnosis

  3. FIXES, a system for automatic selection of set-ups and design of fixtures

    NARCIS (Netherlands)

    Boerma, J.R.; Kals, H.J.J.

    1988-01-01

    This paper reports on the development of a computer aided planning system for the selection of set-ups and the design of fixtures in part manufacturing. First, the bottlenecks in the present planning methods are indicated. A brief description is given of the CAPP environment PART, in which FIXES is

  4. Automatic analysis of selected choroidal diseases in OCT images of the eye fundus

    Science.gov (United States)

    2013-01-01

    Introduction This paper describes a method for automatic analysis of the choroid in OCT images of the eye fundus in ophthalmology. The problem of vascular lesions occurs e.g. in a large population of patients having diabetes or macular degeneration. Their correct diagnosis and quantitative assessment of the treatment progress are a critical part of the eye fundus diagnosis. Material and method The study analysed about 1’000 OCT images acquired using SOCT Copernicus (Optopol Tech. SA, Zawiercie, Poland). The proposed algorithm for image analysis enabled to analyse the texture of the choroid portion located beneath the RPE (Retinal Pigment Epithelium) layer. The analysis was performed using the profiled algorithm based on morphological analysis and texture analysis and a classifier in the form of decision trees. Results The location of the centres of gravity of individual objects present in the image beneath the RPE layer proved to be important in the evaluation of different types of images. In addition, the value of the standard deviation and the number of objects in a scene were equally important. These features enabled classification of three different forms of the choroid that were related to retinal pathology: diabetic edema (the classification gave accuracy ACC1 = 0.73), ischemia of the inner retinal layers (ACC2 = 0.83) and scarring fibro vascular tissue (ACC3 = 0.69). For the cut decision tree the results were as follows: ACC1 = 0.76, ACC2 = 0.81, ACC3 = 0.68. Conclusions The created decision tree enabled to obtain satisfactory results of the classification of three types of choroidal imaging. In addition, it was shown that for the assumed characteristics and the developed classifier, the location of B-scan does not significantly affect the results. The image analysis method for texture analysis presented in the paper confirmed its usefulness in choroid imaging. Currently the application is further studied in the Clinical Department

  5. Automatic Feature Selection and Improved Classification in SICADA Counterfeit Electronics Detection

    Science.gov (United States)

    2017-03-20

    Electronic Parts Can Be Found on Internet Purchasing Platforms. GAO-12-375. (2012). 3. Cobb, W., Lapse, E., Baldwin, R., Temple, M., and Kim, Y . Intrinsic...This analysis approach is a machine learning process that involves four main parts: data collection, feature generation , feature selection, and...this variation maximization occurs indiscriminately, and can separate data within the same class. Further, projection techniques in general

  6. 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

  7. Rational design of chemical ligands for selective mitochondrial targeting

    Czech Academy of Sciences Publication Activity Database

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

    2013-01-01

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

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

    Science.gov (United States)

    2015-03-01

    Yersinia pestis will serve as effective antibiotics by blocking isoprene biosynthesis . In strong support of this hypothesis, we have demonstrated the dose... antibiotic resistant strains and the ease by which antibiotic resistance can be engineered into bacteria further highlights the need for continued...development of novel antibiotics against new bacterial targets. This research project directly addresses this need through the development of a broad spectrum

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

    International Nuclear Information System (INIS)

    Attayek, P.J.; Meyer, E.S.; Lin, L.; Rich, G.C.; Clegg, T.B.; Coronell, O.

    2012-01-01

    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™ 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 4 He 2+ analysis beam are provided.

  10. 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

  11. 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

  12. Signal Transduction and Molecular Targets of Selected Flavonoids

    Science.gov (United States)

    Bode, Ann M.

    2013-01-01

    Abstract Significance: Diet exerts a major influence on the risk for developing cancer and heart disease. Food factors such as flavonoids are alleged to protect cells from premature aging and disease by shielding DNA, proteins, and lipids from oxidative damage. Recent Advances: Our work has focused on clarifying the effects of dietary components on cancer cell proliferation and tumor growth, discovering mechanisms to explain the effects, and identifying the specific molecular targets of these compounds. Our strategy for identifying specific molecular targets of phytochemicals involves the use of supercomputer technology combined with protein crystallography, molecular biology, and experimental laboratory verification. Critical Issues: One of the greatest challenges for scientists is to reduce the accumulation of distortion and half truths reported in the popular media regarding the health benefits of certain foods or food supplements. The use of these is not new, but interest has increased dramatically because of perceived health benefits that are presumably acquired without unpleasant side effects. Flavonoids are touted to exert many beneficial effects in vitro. However, whether they can produce these effects in vivo is disputed. Future Directions: The World Health Organization indicates that one third of all cancer deaths are preventable and that diet is closely linked to prevention. Based on this idea and epidemiological findings, attention has centered on dietary phytochemicals as an effective intervention in cancer development. However, an unequivocal link between diet and cancer has not been established. Thus, identifying cancer preventive dietary agents with specific molecular targets is essential to move forward toward successful cancer prevention. Antioxid. Redox Signal. 19, 163–180. PMID:23458437

  13. Quantitative modeling of selective lysosomal targeting for drug design

    DEFF Research Database (Denmark)

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

    2008-01-01

    Lysosomes are acidic organelles and are involved in various diseases, the most prominent is malaria. Accumulation of molecules in the cell by diffusion from the external solution into cytosol, lysosome and mitochondrium was calculated with the Fick–Nernst–Planck equation. The cell model considers...... the diffusion of neutral and ionic molecules across biomembranes, protonation to mono- or bivalent ions, adsorption to lipids, and electrical attraction or repulsion. Based on simulation results, high and selective accumulation in lysosomes was found for weak mono- and bivalent bases with intermediate to high...... predicted by the model and three were close. Five of the antimalarial drugs were lipophilic weak dibasic compounds. The predicted optimum properties for a selective accumulation of weak bivalent bases in lysosomes are consistent with experimental values and are more accurate than any prior calculation...

  14. Automatic Tool Selection in V-bending Processes by Using an Intelligent Collision Detection Algorithm

    Science.gov (United States)

    Salem, A. A.

    2017-09-01

    V-bending is widely used to produce the sheet metal components. There are global Changes in the shape of the sheet metal component during progressive bending processes. Accordingly, collisions may be occurred between part and tool during bending. Collision-free is considered one of the feasibility conditions of V-bending process planning which the tool selection is verified by the absence of the collisions. This paper proposes an intelligent collision detection algorithm which has the ability to distinguish between 2D bent parts and the other bent parts. Due to this ability, 2D and 3D collision detection subroutines have been developed in the proposed algorithm. This division of algorithm’s subroutines could reduce the computational operations during collisions detecting.

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

    Science.gov (United States)

    Chen, B; Butte, A J

    2016-03-01

    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. © 2015 The Authors Clinical Pharmacology & Therapeutics published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  16. Automatic ROI selection in structural brain MRI using SOM 3D projection.

    Directory of Open Access Journals (Sweden)

    Andrés Ortiz

    Full Text Available This paper presents a method for selecting Regions of Interest (ROI in brain Magnetic Resonance Imaging (MRI for diagnostic purposes, using statistical learning and vector quantization techniques. The proposed method models the distribution of GM and WM tissues grouping the voxels belonging to each tissue in ROIs associated to a specific neurological disorder. Tissue distribution of normal and abnormal images is modelled by a Self-Organizing map (SOM, generating a set of representative prototypes, and the receptive field (RF of each SOM prototype defines a ROI. Moreover, the proposed method computes the relative importance of each ROI by means of its discriminative power. The devised method has been assessed using 818 images from the Alzheimer's disease Neuroimaging Initiative (ADNI which were previously segmented through Statistical Parametric Mapping (SPM. The proposed algorithm was used over these images to parcel ROIs associated to the Alzheimer's Disease (AD. Additionally, this method can be used to extract a reduced set of discriminative features for classification, since it compresses discriminative information contained in the brain. Voxels marked by ROIs which were computed using the proposed method, yield classification results up to 90% of accuracy for controls (CN and Alzheimer's disease (AD patients, and 84% of accuracy for Mild Cognitive Impairment (MCI and AD patients.

  17. Metformin selectively targets redox control of complex I energy transduction

    Directory of Open Access Journals (Sweden)

    Amy R. Cameron

    2018-04-01

    Full Text Available Many guanide-containing drugs are antihyperglycaemic but most exhibit toxicity, to the extent that only the biguanide metformin has enjoyed sustained clinical use. Here, we have isolated unique mitochondrial redox control properties of metformin that are likely to account for this difference. In primary hepatocytes and H4IIE hepatoma cells we found that antihyperglycaemic diguanides DG5-DG10 and the biguanide phenformin were up to 1000-fold more potent than metformin on cell signalling responses, gluconeogenic promoter expression and hepatocyte glucose production. Each drug inhibited cellular oxygen consumption similarly but there were marked differences in other respects. All diguanides and phenformin but not metformin inhibited NADH oxidation in submitochondrial particles, indicative of complex I inhibition, which also corresponded closely with dehydrogenase activity in living cells measured by WST-1. Consistent with these findings, in isolated mitochondria, DG8 but not metformin caused the NADH/NAD+ couple to become more reduced over time and mitochondrial deterioration ensued, suggesting direct inhibition of complex I and mitochondrial toxicity of DG8. In contrast, metformin exerted a selective oxidation of the mitochondrial NADH/NAD+ couple, without triggering mitochondrial deterioration. Together, our results suggest that metformin suppresses energy transduction by selectively inducing a state in complex I where redox and proton transfer domains are no longer efficiently coupled. Keywords: Diabetes, Metformin, Mitochondria, NADH, NAD+

  18. 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.

  19. 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

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

    Science.gov (United States)

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

    2017-12-14

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

  1. Field evaluation of a semi-automatic funnel trap targeted the medically important non-biting flies.

    Science.gov (United States)

    Klong-Klaew, Tunwadee; Sontigun, Narin; Sanit, Sangob; Samerjai, Chutharat; Sukontason, Kom; Kurahashi, Hiromu; Koehler, Philip G; Pereira, Roberto M; Limsopatham, Kwankamol; Suwannayod, Suttida; Thanapornpoonpong, Sa-Nguansak; Chareonviriyaphap, Theeraphap; Sukontason, Kabkaew L

    2017-12-01

    Bait-trapping is a useful approach for monitoring fly population dynamics, and it is an effective tool for physical control of pest species. The aim of this study was to test a newly developed semi-automatic funnel fly trap with some modifications of the former prototype fly trap to study medically important fly population density. The efficacy of the semi-automatic funnel trap was assessed by field sampling during July 2013-June 2014 using 1-day tainted beef offal as bait. The modified semi-automatic funnel traps were able to capture a total of 151,141 adult flies, belonging to the families: Calliphoridae (n=147,248; 97.4%), Muscidae (n=3,124; 2.1%) and Sarcophagidae (n=769; 0.5%), which are the medically important fly species. Among the total of 35 species collected, Chrysomya megacephala (Diptera: Calliphoridae) (n=88,273; 59.95%), Musca domestica (Diptera: Muscidae) (n=1,324; 42.38%) and Boettcherisca peregrina (Diptera: Sarcophagidae) (n=68; 33.01%) were the predominant species of each family. High number of flies was captured in forest area, representing 42.47% (n=64,197) of total specimens. Female flies were trapped more than male with total sex ratio of 0.37 male/female. Flies were trapped throughout the year with peak population in summer. Peak activity was recorded in the afternoon (12.00-18.00h). In summary, the modified semi-automatic funnel fly trap can be used for field collection of the adult fly. By setting the timer, population dynamics, diversity, and periodic activity of adult flies were determined. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. 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.)

  3. 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. Copyright © 2016 Elsevier Ltd. All rights reserved.

  4. On the Selection of Non-Invasive Methods Based on Speech Analysis Oriented to Automatic Alzheimer Disease Diagnosis

    Directory of Open Access Journals (Sweden)

    Unai Martinez de Lizardui

    2013-05-01

    Full Text Available The work presented here is part of a larger study to identify novel technologies and biomarkers for early Alzheimer disease (AD detection and it focuses on evaluating the suitability of a new approach for early AD diagnosis by non-invasive methods. The purpose is to examine in a pilot study the potential of applying intelligent algorithms to speech features obtained from suspected patients in order to contribute to the improvement of diagnosis of AD and its degree of severity. In this sense, Artificial Neural Networks (ANN have been used for the automatic classification of the two classes (AD and control subjects. Two human issues have been analyzed for feature selection: Spontaneous Speech and Emotional Response. Not only linear features but also non-linear ones, such as Fractal Dimension, have been explored. The approach is non invasive, low cost and without any side effects. Obtained experimental results were very satisfactory and promising for early diagnosis and classification of AD patients.

  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. 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. <12 × 12 pixels) point-a...

  7. Goal-driven modulations as a function of time in saccadic target selection

    NARCIS (Netherlands)

    van Zoest, L.J.F.M.; Donk, M.

    2008-01-01

    Four experiments were performed to investigate the contribution of goal-driven modulation in saccadic target selection as a function of time. Observers were required to make an eye movement to a prespecified target that was concurrently presented with multiple nontargets and possibly one distractor.

  8. SU-F-J-34: Automatic Target-Based Patient Positioning Framework for Image-Guided Radiotherapy in Prostate Cancer Treatment

    Energy Technology Data Exchange (ETDEWEB)

    Sasahara, M; Arimura, H; Hirose, T; Ohga, S; Honda, H; Sasaki, T [Kyushu University, Fukuoka (Japan); Shibayama, Y; Umezu, Y [Kyushu University Hospital, Fukuoka (Japan)

    2016-06-15

    Purpose: Current image-guided radiotherapy (IGRT) procedure is bonebased patient positioning, followed by subjective manual correction using cone beam computed tomography (CBCT). This procedure might cause the misalignment of the patient positioning. Automatic target-based patient positioning systems achieve the better reproducibility of patient setup. Our aim of this study was to develop an automatic target-based patient positioning framework for IGRT with CBCT images in prostate cancer treatment. Methods: Seventy-three CBCT images of 10 patients and 24 planning CT images with digital imaging and communications in medicine for radiotherapy (DICOM-RT) structures were used for this study. Our proposed framework started from the generation of probabilistic atlases of bone and prostate from 24 planning CT images and prostate contours, which were made in the treatment planning. Next, the gray-scale histograms of CBCT values within CTV regions in the planning CT images were obtained as the occurrence probability of the CBCT values. Then, CBCT images were registered to the atlases using a rigid registration with mutual information. Finally, prostate regions were estimated by applying the Bayesian inference to CBCT images with the probabilistic atlases and CBCT value occurrence probability. The proposed framework was evaluated by calculating the Euclidean distance of errors between two centroids of prostate regions determined by our method and ground truths of manual delineations by a radiation oncologist and a medical physicist on CBCT images for 10 patients. Results: The average Euclidean distance between the centroids of extracted prostate regions determined by our proposed method and ground truths was 4.4 mm. The average errors for each direction were 1.8 mm in anteroposterior direction, 0.6 mm in lateral direction and 2.1 mm in craniocaudal direction. Conclusion: Our proposed framework based on probabilistic atlases and Bayesian inference might be feasible to

  9. Robustness and precision of an automatic marker detection algorithm for online prostate daily targeting using a standard V-EPID.

    Science.gov (United States)

    Aubin, S; Beaulieu, L; Pouliot, S; Pouliot, J; Roy, R; Girouard, L M; Martel-Brisson, N; Vigneault, E; Laverdière, J

    2003-07-01

    An algorithm for the daily localization of the prostate using implanted markers and a standard video-based electronic portal imaging device (V-EPID) has been tested. Prior to planning, three gold markers were implanted in the prostate of seven patients. The clinical images were acquired with a BeamViewPlus 2.1 V-EPID for each field during the normal course radiotherapy treatment and are used off-line to determine the ability of the automatic marker detection algorithm to adequately and consistently detect the markers. Clinical images were obtained with various dose levels from ranging 2.5 to 75 MU. The algorithm is based on marker attenuation characterization in the portal image and spatial distribution. A total of 1182 clinical images were taken. The results show an average efficiency of 93% for the markers detected individually and 85% for the group of markers. This algorithm accomplishes the detection and validation in 0.20-0.40 s. When the center of mass of the group of implanted markers is used, then all displacements can be corrected to within 1.0 mm in 84% of the cases and within 1.5 mm in 97% of cases. The standard video-based EPID tested provides excellent marker detection capability even with low dose levels. The V-EPID can be used successfully with radiopaque markers and the automatic detection algorithm to track and correct the daily setup deviations due to organ motions.

  10. Quantifying the Tendency of Therapeutic Target Proteins to Bind Promiscuous or Selective Compounds

    Science.gov (United States)

    Hu, Ye; Bajorath, Jürgen

    2015-01-01

    The ability of target proteins to bind structurally diverse compounds and compounds with different degrees of promiscuity (multi-target activity) was systematically assessed on the basis of currently available activity data and target annotations. Intuitive first- and second-order target promiscuity indices were introduced to quantify these binding characteristics and relate them to each other. For compounds and targets, opposite promiscuity trends were observed. Furthermore, the analysis detected many targets that interacted with compounds representing a similar degree of structural diversity but displayed strong tendencies to recognize either promiscuous or selective compounds. Moreover, target families were identified that preferentially interacted with promiscuous compounds. Taken together, these findings further extend our understanding of the molecular basis of polypharmacology. PMID:26000736

  11. Prior Knowledge of Target Direction and Intended Movement Selection Improves Indirect Reaching Movement Decoding.

    Science.gov (United States)

    Li, Hongbao; Hao, Yaoyao; Zhang, Shaomin; Wang, Yiwen; Chen, Weidong; Zheng, Xiaoxiang

    2017-01-01

    Objective. Previous studies have demonstrated that target direction information presented by the dorsal premotor cortex (PMd) during movement planning could be incorporated into neural decoder for achieving better decoding performance. It is still unknown whether the neural decoder combined with only target direction could work in more complex tasks where obstacles impeded direct reaching paths. Methods. In this study, spike activities were collected from the PMd of two monkeys when performing a delayed obstacle-avoidance task. We examined how target direction and intended movement selection were encoded in neuron population activities of the PMd during movement planning. The decoding performances of movement trajectory were compared for three neural decoders with no prior knowledge, or only target direction, or both target direction and intended movement selection integrated into a mixture of trajectory model (MTM). Results. We found that not only target direction but also intended movement selection was presented in neural activities of the PMd during movement planning. It was further confirmed by quantitative analysis. Combined with prior knowledge, the trajectory decoder achieved the best performance among three decoders. Conclusion. Recruiting prior knowledge about target direction and intended movement selection extracted from the PMd could enhance the decoding performance of hand trajectory in indirect reaching movement.

  12. Directional enhancement of selected high-order-harmonics from intense laser irradiated blazed grating targets.

    Science.gov (United States)

    Zhang, Guobo; Chen, Min; Liu, Feng; Yuan, Xiaohui; Weng, Suming; Zheng, Jun; Ma, Yanyun; Shao, Fuqiu; Sheng, Zhengming; Zhang, Jie

    2017-10-02

    Relativistically intense laser solid target interaction has been proved to be a promising way to generate high-order harmonics, which can be used to diagnose ultrafast phenomena. However, their emission direction and spectra still lack tunability. Based upon two-dimensional particle-in-cell simulations, we show that directional enhancement of selected high-order-harmonics can be realized using blazed grating targets. Such targets can select harmonics with frequencies being integer times of the grating frequency. Meanwhile, the radiation intensity and emission area of the harmonics are increased. The emission direction is controlled by tailoring the local blazed structure. Theoretical and electron dynamics analysis for harmonics generation, selection and directional enhancement from the interaction between multi-cycle laser and grating target are carried out. These studies will benefit the generation and application of laser plasma-based high order harmonics.

  13. Detecting signatures of balancing selection to identify targets of anti-parasite immunity.

    Science.gov (United States)

    Weedall, Gareth D; Conway, David J

    2010-07-01

    Parasite antigen genes might evolve under frequency-dependent immune selection. The distinctive patterns of polymorphism that result can be detected using population genetic methods that test for signatures of balancing selection, allowing genes encoding important targets of immunity to be identified. Analyses can be complicated by population structures, histories and features of a parasite's genome. However, new sequencing technologies facilitate scans of polymorphism throughout parasite genomes to identify the most exceptional gene specific signatures. We focus on malaria parasites to illustrate challenges and opportunities for detecting targets of frequency-dependent immune selection to discover new potential vaccine candidates. Copyright 2010 Elsevier Ltd. All rights reserved.

  14. 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.

  15. Automatic Feature Selection and Weighting for the Formation of Homogeneous Groups for Regional Intensity-Duration-Frequency (IDF) Curve Estimation

    Science.gov (United States)

    Yang, Z.; Burn, D. H.

    2017-12-01

    Extreme rainfall events can have devastating impacts on society. To quantify the associated risk, the IDF curve has been used to provide the essential rainfall-related information for urban planning. However, the recent changes in the rainfall climatology caused by climate change and urbanization have made the estimates provided by the traditional regional IDF approach increasingly inaccurate. This inaccuracy is mainly caused by two problems: 1) The ineffective choice of similarity indicators for the formation of a homogeneous group at different regions; and 2) An inadequate number of stations in the pooling group that does not adequately reflect the optimal balance between group size and group homogeneity or achieve the lowest uncertainty in the rainfall quantiles estimates. For the first issue, to consider the temporal difference among different meteorological and topographic indicators, a three-layer design is proposed based on three stages in the extreme rainfall formation: cloud formation, rainfall generation and change of rainfall intensity above urban surface. During the process, the impacts from climate change and urbanization are considered through the inclusion of potential relevant features at each layer. Then to consider spatial difference of similarity indicators for the homogeneous group formation at various regions, an automatic feature selection and weighting algorithm, specifically the hybrid searching algorithm of Tabu search, Lagrange Multiplier and Fuzzy C-means Clustering, is used to select the optimal combination of features for the potential optimal homogenous groups formation at a specific region. For the second issue, to compare the uncertainty of rainfall quantile estimates among potential groups, the two sample Kolmogorov-Smirnov test-based sample ranking process is used. During the process, linear programming is used to rank these groups based on the confidence intervals of the quantile estimates. The proposed methodology fills the gap

  16. Molecular Connectivity Predefines Polypharmacology: Aliphatic Rings, Chirality, and sp3 Centers Enhance Target Selectivity

    Directory of Open Access Journals (Sweden)

    Stefania Monteleone

    2017-08-01

    Full Text Available Dark chemical matter compounds are small molecules that have been recently identified as highly potent and selective hits. For this reason, they constitute a promising class of possible candidates in the process of drug discovery and raise the interest of the scientific community. To this purpose, Wassermann et al. (2015 have described the application of 2D descriptors to characterize dark chemical matter. However, their definition was based on the number of reported positive assays rather than the number of known targets. As there might be multiple assays for one single target, the number of assays does not fully describe target selectivity. Here, we propose an alternative classification of active molecules that is based on the number of known targets. We cluster molecules in four classes: black, gray, and white compounds are active on one, two to four, and more than four targets respectively, whilst inactive compounds are found to be inactive in the considered assays. In this study, black and inactive compounds are found to have not only higher solubility, but also a higher number of chiral centers, sp3 carbon atoms and aliphatic rings. On the contrary, white compounds contain a higher number of double bonds and fused aromatic rings. Therefore, the design of a screening compound library should consider these molecular properties in order to achieve target selectivity or polypharmacology. Furthermore, analysis of four main target classes (GPCRs, kinases, proteases, and ion channels shows that GPCR ligands are more selective than the other classes, as the number of black compounds is higher in this target superfamily. On the other side, ligands that hit kinases, proteases, and ion channels bind to GPCRs more likely than to other target classes. Consequently, depending on the target protein family, appropriate screening libraries can be designed in order to minimize the likelihood of unwanted side effects early in the drug discovery process

  17. 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

  18. Automation of cellular therapy product manufacturing: results of a split validation comparing CD34 selection of peripheral blood stem cell apheresis product with a semi-manual vs. an automatic procedure.

    Science.gov (United States)

    Hümmer, Christiane; Poppe, Carolin; Bunos, Milica; Stock, Belinda; Wingenfeld, Eva; Huppert, Volker; Stuth, Juliane; Reck, Kristina; Essl, Mike; Seifried, Erhard; Bonig, Halvard

    2016-03-16

    Automation of cell therapy manufacturing promises higher productivity of cell factories, more economical use of highly-trained (and costly) manufacturing staff, facilitation of processes requiring manufacturing steps at inconvenient hours, improved consistency of processing steps and other benefits. One of the most broadly disseminated engineered cell therapy products is immunomagnetically selected CD34+ hematopoietic "stem" cells (HSCs). As the clinical GMP-compliant automat CliniMACS Prodigy is being programmed to perform ever more complex sequential manufacturing steps, we developed a CD34+ selection module for comparison with the standard semi-automatic CD34 "normal scale" selection process on CliniMACS Plus, applicable for 600 × 10(6) target cells out of 60 × 10(9) total cells. Three split-validation processings with healthy donor G-CSF-mobilized apheresis products were performed; feasibility, time consumption and product quality were assessed. All processes proceeded uneventfully. Prodigy runs took about 1 h longer than CliniMACS Plus runs, albeit with markedly less hands-on operator time and therefore also suitable for less experienced operators. Recovery of target cells was the same for both technologies. Although impurities, specifically T- and B-cells, were 5 ± 1.6-fold and 4 ± 0.4-fold higher in the Prodigy products (p = ns and p = 0.013 for T and B cell depletion, respectively), T cell contents per kg of a virtual recipient receiving 4 × 10(6) CD34+ cells/kg was below 10 × 10(3)/kg even in the worst Prodigy product and thus more than fivefold below the specification of CD34+ selected mismatched-donor stem cell products. The products' theoretical clinical usability is thus confirmed. This split validation exercise of a relatively short and simple process exemplifies the potential of automatic cell manufacturing. Automation will further gain in attractiveness when applied to more complex processes, requiring frequent interventions or handling at

  19. An Automatic Target Detection Algorithm for Swath Sonar Backscatter Imagery, Using Image Texture and Independent Component Analysis

    Directory of Open Access Journals (Sweden)

    Elias Fakiris

    2016-04-01

    Full Text Available In the present paper, a methodological scheme, bringing together common Acoustic Seabed Classification (ASC systems and a powerful data decomposition approach, called Independent Component Analysis (ICA, is demonstrated regarding its suitability for detecting small targets in Side Scan Sonar imagery. Traditional ASC systems extract numerous texture descriptors, leading to a large feature vector, the dimensionality of which is reduced by means of data decomposition techniques, usually Principal Component Analysis (PCA, prior to classification. However, in the target detection issue, data decomposition should point towards finding components that represent sub-ordinary image information (i.e., small targets rather than a dominant one. ICA has long been proved to be suitable for separating targets from a background, and this study represents a novel exhibition of its applicability to Side Scan Sonar (SSS images. The present study attempts to build a fully automated target detection approach that combines image based feature extraction, ICA, and unsupervised classification. The suitability of the proposed approach has been demonstrated using an SSS data-set containing more than 70 manmade targets, most of them metallic, validated through a marine magnetic survey or ground truthing inspection. The method exhibited very good performance as it was able to detect more than 77% of the targets and it produced less than seven false alarms per km2. Moreover, it was compared to cases where, in the exact same methodological scheme, no decomposition technique is used, or PCA is employed instead of ICA, achieving the highest detection rate, but, more importantly, producing more than six times less false alarms, thus proving that ICA successfully manages to maximize target to background separation.

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

    Science.gov (United States)

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

    2017-12-01

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

  1. Occurrence Prospect of HDR and Target Site Selection Study in Southeastern of China

    Science.gov (United States)

    Lin, W.; Gan, H.

    2017-12-01

    Hot dry rock (HDR) geothermal resource is one of the most important clean energy in future. Site selection a HDR resource is a fundamental work to explore the HDR resources. This paper compiled all the HDR development projects domestic and abroad, and summarized the location of HDR geothermal geological index. After comparing the geological background of HDR in the southeast coastal area of China, Yangjiang Xinzhou in Guangdong province, Leizhou Peninsula area, Lingshui in Hainan province and Huangshadong in Guangzhou were selected from some key potential target area along the southeast coast of China. Deep geothermal field model of the study area is established based on the comprehensive analysis of the target area of deep geothermal geological background and deep thermal anomalies. This paper also compared the hot dry rock resources target locations, and proposed suggestions for the priority exploration target area and exploration scheme.

  2. Comparison of automatic procedures in the selection of peaks over threshold in flood frequency analysis: A Canadian case study in the context of climate change

    Science.gov (United States)

    Durocher, M.; Mostofi Zadeh, S.; Burn, D. H.; Ashkar, F.

    2017-12-01

    Floods are one of the most costly hazards and frequency analysis of river discharges is an important part of the tools at our disposal to evaluate their inherent risks and to provide an adequate response. In comparison to the common examination of annual streamflow maximums, peaks over threshold (POT) is an interesting alternative that makes better use of the available information by including more than one flood event per year (on average). However, a major challenge is the selection of a satisfactory threshold above which peaks are assumed to respect certain conditions necessary for an adequate estimation of the risk. Additionally, studies have shown that POT is also a valuable approach to investigate the evolution of flood regimes in the context of climate change. Recently, automatic procedures for the selection of the threshold were suggested to guide that important choice, which otherwise rely on graphical tools and expert judgment. Furthermore, having an automatic procedure that is objective allows for quickly repeating the analysis on a large number of samples, which is useful in the context of large databases or for uncertainty analysis based on a resampling approach. This study investigates the impact of considering such procedures in a case study including many sites across Canada. A simulation study is conducted to evaluate the bias and predictive power of the automatic procedures in similar conditions as well as investigating the power of derived nonstationarity tests. The results obtained are also evaluated in the light of expert judgments established in a previous study. Ultimately, this study provides a thorough examination of the considerations that need to be addressed when conducting POT analysis using automatic threshold selection.

  3. 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.

  4. Social exclusion impairs distractor suppression but not target enhancement in selective attention.

    Science.gov (United States)

    Xu, Mengsi; Li, Zhiai; Diao, Liuting; Fan, Lingxia; Zhang, Lijie; Yuan, Shuge; Yang, Dong

    2017-11-01

    Social exclusion has been thought to weaken one's ability to exert inhibitory control. Existing studies have primarily focused on the relationship between exclusion and behavioral inhibition, and have reported that exclusion impairs behavioral inhibition. However, whether exclusion also affects selective attention, another important aspect of inhibitory control, remains unknown. Therefore, the current study aimed to explore whether social exclusion impairs selective attention, and to specifically examine its effect on two hypothesized mechanisms of selective attention: target enhancement and distractor suppression. The Cyberball game was used to manipulate social exclusion. Participants then performed a visual search task while event-related potentials were recorded. In the visual search task, target and salient distractor were either both presented laterally or one was presented on the vertical midline and the other laterally. Results showed that social exclusion differentially affected target and distractor processing. While exclusion impaired distractor suppression, reflected as smaller distractor-positivity (Pd) amplitudes for the exclusion group compared to the inclusion group, it did not affect target enhancement, reflected as similar target-negativity (Nt) amplitudes for both the exclusion and inclusion groups. Together, these results extend our understanding of the relationship between exclusion and inhibitory control, and suggest that social exclusion affects selective attention in a more complex manner than previously thought. Copyright © 2017. Published by Elsevier B.V.

  5. 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.

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

    Science.gov (United States)

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

    2016-09-01

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

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

    Directory of Open Access Journals (Sweden)

    Manuela Sironi

    2016-09-01

    Full Text Available 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

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

    Science.gov (United States)

    Zhou, Wenke; Huang, Juan; Watson, Annie M; Hong, Yang

    2012-01-01

    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.

  9. In silico tools used for compound selection during target-based drug discovery and development.

    Science.gov (United States)

    Caldwell, Gary W

    2015-01-01

    The target-based drug discovery process, including target selection, screening, hit-to-lead (H2L) and lead optimization stage gates, is the most common approach used in drug development. The full integration of in vitro and/or in vivo data with in silico tools across the entire process would be beneficial to R&D productivity by developing effective selection criteria and drug-design optimization strategies. This review focuses on understanding the impact and extent in the past 5 years of in silico tools on the various stage gates of the target-based drug discovery approach. There are a large number of in silico tools available for establishing selection criteria and drug-design optimization strategies in the target-based approach. However, the inconsistent use of in vitro and/or in vivo data integrated with predictive in silico multiparameter models throughout the process is contributing to R&D productivity issues. In particular, the lack of reliable in silico tools at the H2L stage gate is contributing to the suboptimal selection of viable lead compounds. It is suggested that further development of in silico multiparameter models and organizing biologists, medicinal and computational chemists into one team with a single accountable objective to expand the utilization of in silico tools in all phases of drug discovery would improve R&D productivity.

  10. THE SDSS-IV EXTENDED BARYON OSCILLATION SPECTROSCOPIC SURVEY: LUMINOUS RED GALAXY TARGET SELECTION

    Energy Technology Data Exchange (ETDEWEB)

    Prakash, Abhishek; Licquia, Timothy C.; Newman, Jeffrey A.; Rao, Sandhya M. [PITT PACC, Department of Physics and Astronomy, University of Pittsburgh, Pittsburgh, PA 15260 (United States); Ross, Ashley J. [Center for Cosmology and Astro-Particle Physics, Ohio State University, Columbus, OH 43210 (United States); Myers, Adam D. [Department of Physics and Astronomy, University of Wyoming, Laramie, WY 82071 (United States); Dawson, Kyle S.; Bautista, Julian E.; Brownstein, Joel R. [Department of Physics and Astronomy, University of Utah, Salt Lake City, UT 84112 (United States); Kneib, Jean-Paul [Laboratoire d’Astrophysique, Ecole Polytechnique Fédérale de Lausanne Observatoire de Sauverny, 1290 Versoix (Switzerland); Percival, Will J. [Institute of Cosmology and Gravitation, Dennis Sciama Building, University of Portsmouth, Portsmouth, PO1 3FX (United Kingdom); Comparat, Johan [Instituto de Física Teórica, (UAM/CSIC), Universidad Autónoma de Madrid, Cantoblanco, E-28049 Madrid (Spain); Tinker, Jeremy L. [Center for Cosmology and Particle Physics, Department of Physics, New York University, 4 Washington Place, New York, NY 10003 (United States); Schlegel, David J. [Lawrence Berkeley National Laboratory, One Cyclotron Road, Berkeley, CA 94720 (United States); Tojeiro, Rita [School of Physics and Astronomy, St Andrews, KY16 9SS (United Kingdom); Ho, Shirley; Lang, Dustin [Bruce and Astrid McWilliams Center for Cosmology, Department of Physics, Carnegie Mellon University, 5000 Forbes Avenue, Pittsburgh, PA 15213 (United States); McBride, Cameron K. [Harvard-Smithsonian Center for Astrophysics, Harvard University, 60 Garden Street, Cambridge, MA 02138 (United States); Zhu, Guangtun Ben, E-mail: abp15@pitt.edu [Department of Physics and Astronomy, Johns Hopkins University, Baltimore, MD 21218 (United States); and others

    2016-06-01

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

  11. Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

    DEFF Research Database (Denmark)

    Spiess, Katja; Jeppesen, Mads G.; Malmgaard-Clausen, Mikkel

    2017-01-01

    Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment ...

  12. Mature Epitope Density - A strategy for target selection based on immunoinformatics and exported prokaryotic proteins

    DEFF Research Database (Denmark)

    Santos, Anderson R; Pereira, Vanessa Bastos; Barbosa, Eudes

    2013-01-01

    . However, currently available tools do not account for the concentration of epitope products in the mature protein product and its relation to the reliability of target selection. RESULTS: We developed a computational strategy based on measuring the epitope's concentration in the mature protein, called...

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

    Science.gov (United States)

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

    2008-04-01

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

  14. 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

  15. 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.

  16. Treatment Strategies that Enhance the Efficacy and Selectivity of Mitochondria-Targeted Anticancer Agents

    Directory of Open Access Journals (Sweden)

    Josephine S. Modica-Napolitano

    2015-07-01

    Full Text Available Nearly a century has passed since Otto Warburg first observed high rates of aerobic glycolysis in a variety of tumor cell types and suggested that this phenomenon might be due to an impaired mitochondrial respiratory capacity in these cells. Subsequently, much has been written about the role of mitochondria in the initiation and/or progression of various forms of cancer, and the possibility of exploiting differences in mitochondrial structure and function between normal and malignant cells as targets for cancer chemotherapy. A number of mitochondria-targeted compounds have shown efficacy in selective cancer cell killing in pre-clinical and early clinical testing, including those that induce mitochondria permeability transition and apoptosis, metabolic inhibitors, and ROS regulators. To date, however, none has exhibited the standards for high selectivity and efficacy and low toxicity necessary to progress beyond phase III clinical trials and be used as a viable, single modality treatment option for human cancers. This review explores alternative treatment strategies that have been shown to enhance the efficacy and selectivity of mitochondria-targeted anticancer agents in vitro and in vivo, and may yet fulfill the clinical promise of exploiting the mitochondrion as a target for cancer chemotherapy.

  17. Design, construction, and characterization of high-performance membrane fusion devices with target-selectivity.

    Science.gov (United States)

    Kashiwada, Ayumi; Yamane, Iori; Tsuboi, Mana; Ando, Shun; Matsuda, Kiyomi

    2012-01-31

    Membrane fusion proteins such as the hemagglutinin glycoprotein have target recognition and fusion accelerative domains, where some synergistically working elements are essential for target-selective and highly effective native membrane fusion systems. In this work, novel membrane fusion devices bearing such domains were designed and constructed. We selected a phenylboronic acid derivative as a recognition domain for a sugar-like target and a transmembrane-peptide (Leu-Ala sequence) domain interacting with the target membrane, forming a stable hydrophobic α-helix and accelerating the fusion process. Artificial membrane fusion behavior between the synthetic devices in which pilot and target liposomes were incorporated was characterized by lipid-mixing and inner-leaflet lipid-mixing assays. Consequently, the devices bearing both the recognition and transmembrane domains brought about a remarkable increase in the initial rate for the membrane fusion compared with the devices containing the recognition domain alone. In addition, a weakly acidic pH-responsive device was also constructed by replacing three Leu residues in the transmembrane-peptide domain by Glu residues. The presence of Glu residues made the acidic pH-dependent hydrophobic α-helix formation possible as expected. The target-selective liposome-liposome fusion was accelerated in a weakly acidic pH range when the Glu-substituted device was incorporated in pilot liposomes. The use of this pH-responsive device seems to be a potential strategy for novel applications in a liposome-based delivery system. © 2011 American Chemical Society

  18. Novel Chemokine-Based Immunotoxins for Potent and Selective Targeting of Cytomegalovirus Infected Cells

    Directory of Open Access Journals (Sweden)

    Katja Spiess

    2017-01-01

    Full Text Available Immunotoxins as antiviral therapeutics are largely unexplored but have promising prospective due to their high selectivity potential and their unparalleled efficiency. One recent example targeted the virus-encoded G protein-coupled receptor US28 as a strategy for specific and efficient treatment of human cytomegalovirus (HCMV infections. US28 is expressed on virus-infected cells and scavenge chemokines by rapid internalization. The chemokine-based fusion-toxin protein (FTP consisted of a variant (F49A of CX3CL1 specifically targeting US28 linked to the catalytic domain of Pseudomonas exotoxin A (PE. Here, we systematically seek to improve F49A-FTP by modifications in its three structural domains; we generated variants with (1 altered chemokine sequence (K14A, F49L, and F49E, (2 shortened and elongated linker region, and (3 modified toxin domain. Only F49L-FTP displayed higher selectivity in its binding to US28 versus CX3CR1, the endogenous receptor for CX3CL1, but this was not matched by a more selective killing of US28-expressing cells. A longer linker and different toxin variants decreased US28 affinity and selective killing. Thereby, F49A-FTP represents the best candidate for HCMV treatment. Many viruses encode internalizing receptors suggesting that not only HCMV but also, for instance, Epstein-Barr virus and Kaposi’s sarcoma-associated herpesvirus may be targeted by FTPs.

  19. Out with the old? The role of selective attention in retaining targets in partial report.

    Science.gov (United States)

    Lindsey, Dakota R B; Bundesen, Claus; Kyllingsbæk, Søren; Petersen, Anders; Logan, Gordon D

    2017-01-01

    In the partial-report task, subjects are asked to report only a portion of the items presented. Selective attention chooses which objects to represent in short-term memory (STM) on the basis of their relevance. Because STM is limited in capacity, one must sometimes choose which objects are removed from memory in light of new relevant information. We tested the hypothesis that the choices among newly presented information and old information in STM involve the same process-that both are acts of selective attention. We tested this hypothesis using a two-display partial-report procedure. In this procedure, subjects had to select and retain relevant letters (targets) from two sequentially presented displays. If selection in perception and retention in STM are the same process, then irrelevant letters (distractors) in the second display, which demanded attention because of their similarity to the targets, should have decreased target report from the first display. This effect was not obtained in any of four experiments. Thus, choosing objects to keep in STM is not the same process as choosing new objects to bring into STM.

  20. 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.

  1. Gene expression levels are a target of recent natural selection in the human genome.

    Science.gov (United States)

    Kudaravalli, Sridhar; Veyrieras, Jean-Baptiste; Stranger, Barbara E; Dermitzakis, Emmanouil T; Pritchard, Jonathan K

    2009-03-01

    Changes in gene expression may represent an important mode of human adaptation. However, to date, there are relatively few known examples in which selection has been shown to act directly on levels or patterns of gene expression. In order to test whether single nucleotide polymorphisms (SNPs) that affect gene expression in cis are frequently targets of positive natural selection in humans, we analyzed genome-wide SNP and expression data from cell lines associated with the International HapMap Project. Using a haplotype-based test for selection that was designed to detect incomplete selective sweeps, we found that SNPs showing signals of selection are more likely than random SNPs to be associated with gene expression levels in cis. This signal is significant in the Yoruba (which is the population that shows the strongest signals of selection overall) and shows a trend in the same direction in the other HapMap populations. Our results argue that selection on gene expression levels is an important type of human adaptation. Finally, our work provides an analytical framework for tackling a more general problem that will become increasingly important: namely, testing whether selection signals overlap significantly with SNPs that are associated with phenotypes of interest.

  2. WE-AB-BRA-09: Registration of Preoperative MRI to Intraoperative Radiographs for Automatic Vertebral Target Localization

    Energy Technology Data Exchange (ETDEWEB)

    De Silva, T; Uneri, A; Ketcha, M; Reaungamornrat, S; Goerres, J [Johns Hopkins University, Baltimore, MD (United States); Vogt, S; Kleinszig, G [Siemens Healthcare, Erlangen (Germany); Wolinsky, J [The Johns Hopkins Hospital, Baltimore, MD (United States); Siewerdsen, JH

    2016-06-15

    Purpose: Accurate localization of target vertebrae is essential to safe, effective spine surgery, but wrong-level surgery occurs with surprisingly high frequency. Recent research yielded the “LevelCheck” method for 3D-2D registration of preoperative CT to intraoperative radiographs, providing decision support for level localization. We report a new method (MR-LevelCheck) to perform 3D-2D registration based on preoperative MRI, presenting a solution for the increasingly common scenario in which MRI (not CT) is used for preoperative planning. Methods: Direct extension of LevelCheck is confounded by large mismatch in image intensity between MRI and radiographs. The proposed method overcomes such challenges with a simple vertebrae segmentation. Using seed points at centroids, vertebrae are segmented using continuous max-flow method and dilated by 1.8 mm to include surrounding cortical bone (inconspicuous in T2w-MRI). MRI projections are computed (analogous to DRR) using segmentation and registered to intraoperative radiographs. The method was tested in a retrospective IRB-approved study involving 11 patients undergoing cervical, thoracic, or lumbar spine surgery following preoperative MRI. Registration accuracy was evaluated in terms of projection-distance-error (PDE) between the true and estimated location of vertebrae in each radiograph. Results: The method successfully registered each preoperative MRI to intraoperative radiographs and maintained desirable properties of robustness against image content mismatch, and large capture range. Segmentation achieved Dice coefficient = 89.2 ± 2.3 and mean-absolute-distance (MAD) = 1.5 ± 0.3 mm. Registration demonstrated robust performance under realistic patient variations, with PDE = 4.0 ± 1.9 mm (median ± iqr) and converged with run-time = 23.3 ± 1.7 s. Conclusion: The MR-LevelCheck algorithm provides an important extension to a previously validated decision support tool in spine surgery by extending its utility to

  3. 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.

  4. Specific and selective target detection of supra-genome 21 Mers Salmonella via silicon nanowires biosensor

    Science.gov (United States)

    Mustafa, Mohammad Razif Bin; Dhahi, Th S.; Ehfaed, Nuri. A. K. H.; Adam, Tijjani; Hashim, U.; Azizah, N.; Mohammed, Mohammed; Noriman, N. Z.

    2017-09-01

    The nano structure based on silicon can be surface modified to be used as label-free biosensors that allow real-time measurements. The silicon nanowire surface was functionalized using 3-aminopropyltrimethoxysilane (APTES), which functions as a facilitator to immobilize biomolecules on the silicon nanowire surface. The process is simple, economical; this will pave the way for point-of-care applications. However, the surface modification and subsequent detection mechanism still not clear. Thus, study proposed step by step process of silicon nano surface modification and its possible in specific and selective target detection of Supra-genome 21 Mers Salmonella. The device captured the molecule with precisely; the approach took the advantages of strong binding chemistry created between APTES and biomolecule. The results indicated how modifications of the nanowires provide sensing capability with strong surface chemistries that can lead to specific and selective target detection.

  5. Diverse Actions and Target-Site Selectivity of Neonicotinoids: Structural Insights

    Science.gov (United States)

    Matsuda, Kazuhiko; Kanaoka, Satoshi; Akamatsu, Miki; Sattelle, David B.

    2009-01-01

    The nicotinic acetylcholine receptors (nAChRs) are targets for human and veterinary medicines as well as insecticides. Subtype-selectivity among the diverse nAChR family members is important for medicines targeting particular disorders, and pest-insect selectivity is essential for the development of safer, environmentally acceptable insecticides. Neonicotinoid insecticides selectively targeting insect nAChRs have important applications in crop protection and animal health. Members of this class exhibit strikingly diverse actions on their nAChR targets. Here we review the chemistry and diverse actions of neonicotinoids on insect and mammalian nAChRs. Electrophysiological studies on native nAChRs and on wild-type and mutagenized recombinant nAChRs have shown that basic residues particular to loop D of insect nAChRs are likely to interact electrostatically with the nitro group of neonicotinoids. In 2008, the crystal structures were published showing neonicotinoids docking into the acetylcholine binding site of molluscan acetylcholine binding proteins with homology to the ligand binding domain (LBD) of nAChRs. The crystal structures showed that 1) glutamine in loop D, corresponding to the basic residues of insect nAChRs, hydrogen bonds with the NO2 group of imidacloprid and 2) neonicotinoid-unique stacking and CH-π bonds at the LBD. A neonicotinoid-resistant strain obtained by laboratory-screening has been found to result from target site mutations, and possible reasons for this are also suggested by the crystal structures. The prospects of designing neonicotinoids that are safe not only for mammals but also for beneficial insects such as honey bees (Apis mellifera) are discussed in terms of interactions with non-α nAChR subunits. PMID:19321668

  6. Ethyl Pyruvate: An Anti-Microbial Agent that Selectively Targets Pathobionts and Biofilms

    OpenAIRE

    Debebe, Tewodros; Kr?ger, Monika; Huse, Klaus; Kacza, Johannes; M?hlberg, Katja; K?nig, Brigitte; Birkenmeier, Gerd

    2016-01-01

    The microbiota has a strong influence on health and disease in humans. A causative shift favoring pathobionts is strongly linked to diseases. Therefore, anti-microbial agents selectively targeting potential pathogens as well as their biofilms are urgently demanded. Here we demonstrate the impact of ethyl pyruvate, so far known as ROS scavenger and anti-inflammatory agent, on planktonic microbes and biofilms. Ethyl pyruvate combats preferably the growth of pathobionts belonging to bacteria and...

  7. Selective Targeting of Antiviral and Immunomodulating Agents in the Treatment of Arenavirus Infections

    Science.gov (United States)

    1987-10-01

    designated by other authorized documents. aCURqY CLASIFICATION OF THIS PAGE R T M A PForm Approved REPORT DOCUMEN[ATION PAGE OMB No. 0704-0188 la...protected mice from viral infections in which the liver or lung served as the primary site of virus infection. Liposome-encapsulated ribavirin was more...report summarizes our findings using liposomes as carriers for the selective targeting of antiviral and immunomodulating agents in viral infections

  8. Designing the nanobiointerface of fluorescent nanodiamonds: highly selective targeting of glioma cancer cells.

    Science.gov (United States)

    Slegerova, Jitka; Hajek, Miroslav; Rehor, Ivan; Sedlak, Frantisek; Stursa, Jan; Hruby, Martin; Cigler, Petr

    2015-01-14

    Core-shell nanoparticles based on fluorescent nanodiamonds coated with a biocompatible N-(2-hydroxypropyl)methacrylamide copolymer shell were developed for background-free near-infrared imaging of cancer cells. The particles showed excellent colloidal stability in buffers and culture media. After conjugation with a cyclic RGD peptide they selectively targeted integrin αvβ3 receptors on glioblastoma cells with high internalization efficacy.

  9. Mitochondrial permeability transition pore as a selective target for anti-cancer therapy

    Directory of Open Access Journals (Sweden)

    Dong Hoon eSuh

    2013-03-01

    Full Text Available Mitochondrial outer membrane permeabilization (MOMP is the ultimate step in dozens of lethal apoptotic signal transduction pathways which converge on mitochondria. One of the representative systems proposed to be responsible for the MOMP is the mitochondrial permeability transition pore (MPTP. Although the molecular composition of the MPTP is not clearly understood, the MPTP attracts much interest as a promising target for resolving two conundrums regarding cancer treatment: tumor selectivity and resistance to treatment. The regulation of the MPTP is closely related to metabolic reprogramming in cancer cells including mitochondrial alterations. Restoration of deregulated apoptotic machinery in cancer cells by tumor-specific modulation of the MPTP could therefore be a promising anti-cancer strategy. Currently, a number of MPTP-targeting agents are under pre-clinical and clinical studies. Here, we reviewed the structure and regulation of the MPTP as well as the current status of the development of promising MPTP-targeting drugs.

  10. The TESS Input Catalog and Selection of Targets for the TESS Transit Search

    Science.gov (United States)

    Pepper, Joshua; Stassun, Keivan G.; Paegert, Martin; Oelkers, Ryan; De Lee, Nathan Michael; Torres, Guillermo; TESS Target Selection Working Group

    2018-01-01

    The TESS mission will photometrically survey millions of the brightest stars over almost the entire the sky to detect transiting exoplanets. A key step to enable that search is the creation of the TESS Input Catalog (TIC), a compiled catalog of 700 million stars and galaxies with observed and calculated parameters. From the TIC we derive the Candidate Target List (CTL) to identify target stars for the 2-minute TESS postage stamps. The CTL is designed to identify the best stars for the detection of small planets, which includes all bright cool dwarf stars in the sky. I will describe the target selection strategy, the distribution of stars in the current CTL, and how both the TIC and CTL will expand and improve going forward.

  11. 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.

  12. Chlorin e6 Conjugated Interleukin-6 Receptor Aptamers Selectively Kill Target Cells Upon Irradiation

    Directory of Open Access Journals (Sweden)

    Sven Kruspe

    2014-01-01

    Full Text Available Photodynamic therapy (PDT uses the therapeutic properties of light in combination with certain chemicals, called photosensitizers, to successfully treat brain, breast, prostate, and skin cancers. To improve PDT, current research focuses on the development of photosensitizers to specifically target cancer cells. In the past few years, aptamers have been developed to directly deliver cargo molecules into target cells. We conjugated the photosensitizer chlorin e6 (ce6 with a human interleukin-6 receptor (IL-6R binding RNA aptamer, AIR-3A yielding AIR-3A-ce6 for application in high efficient PDT. AIR-3A-ce6 was rapidly and specifically internalized by IL-6R presenting (IL-6R+ cells. Upon light irradiation, targeted cells were selectively killed, while free ce6 did not show any toxic effect. Cells lacking the IL-6R were also not affected by AIR-3A-ce6. With this approach, we improved the target specificity of ce6-mediated PDT. In the future, other tumor-specific aptamers might be used to selectively localize photosensitizers into cells of interest and improve the efficacy and specificity of PDT in cancer and other diseases.

  13. Merger and Acquisition Target Selection Based on Interval Neutrosophic Multigranulation Rough Sets over Two Universes

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2017-07-01

    Full Text Available As a significant business activity, merger and acquisition (M&A generally means transactions in which the ownership of companies, other business organizations or their operating units are transferred or combined. In a typical M&A procedure, M&A target selection is an important issue that tends to exert an increasingly significant impact on different business areas. Although some research works based on fuzzy methods have been explored on this issue, they can only deal with incomplete and uncertain information, but not inconsistent and indeterminate information that exists universally in the decision making process. Additionally, it is advantageous to solve M&A problems under the group decision making context. In order to handle these difficulties in M&A target selection background, we introduce a novel rough set model by combining interval neutrosophic sets (INSs with multigranulation rough sets over two universes, called an interval neutrosophic (IN multigranulation rough set over two universes. Then, we discuss the definition and some fundamental properties of the proposed model. Finally, we establish decision making rules and computing approaches for the proposed model in M&A target selection background, and the effectiveness of the decision making approach is demonstrated by an illustrative case analysis.

  14. Efficient and Adaptive Node Selection for Target Tracking in Wireless Sensor Network

    Directory of Open Access Journals (Sweden)

    Juan Feng

    2016-01-01

    Full Text Available In target tracking wireless sensor network, choosing the proper working nodes can not only minimize the number of active nodes, but also satisfy the tracking reliability requirement. However, most existing works focus on selecting sensor nodes which are the nearest to the target for tracking missions and they did not consider the correlation of the location of the sensor nodes so that these approaches can not meet all the goals of the network. This work proposes an efficient and adaptive node selection approach for tracking a target in a distributed wireless sensor network. The proposed approach combines the distance-based node selection strategy and particle filter prediction considering the spatial correlation of the different sensing nodes. Moreover, a joint distance weighted measurement is proposed to estimate the information utility of sensing nodes. Experimental results show that EANS outperformed the state-of-the-art approaches by reducing the energy cost and computational complexity as well as guaranteeing the tracking accuracy.

  15. 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. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  16. 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

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

    Energy Technology Data Exchange (ETDEWEB)

    Chandonia, John-Marc; Brenner, Steven E.

    2004-07-14

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

  18. Body condition score as a selection tool for targeted selective treatment-based nematode control strategies in Merino ewes.

    Science.gov (United States)

    Cornelius, M P; Jacobson, C; Besier, R B

    2014-12-15

    Sheep nematode control utilising refugia-based strategies have been shown to delay anthelmintic resistance, but the optimal indices to select individuals to be left untreated under extensive sheep grazing conditions are not clear. This experiment tested the hypothesis that high body condition can indicate ability of mature sheep to better cope with worms and therefore remain untreated in a targeted treatment programme. Adult Merino ewes from flocks on two private farms located in south-west Western Australia (Farm A, n = 271, and Farm B, n = 258) were measured for body condition score (BCS), body weight and worm egg counts (WEC) on four occasions between May and December (pre-lambing, lamb marking, lamb weaning and post-weaning). Half of the ewes in each flock received anthelmintic treatments to suppress WEC over the experimental period and half remained untreated (unless critical limits were reached). Response to treatment was analysed in terms of BCS change and percentage live weight change. No effect of high or low initial WEC groups was shown for BCS response, and liveweight responses were inconsistent. A relatively greater BCS response to treatment was observed in ewes in low BCS pre-lambing compared to better-conditioned ewes on one farm where nutrition was sub-optimal and worm burdens were high. Sheep in low body condition pre-lambing were more than three times more likely to fall into a critically low BCS (<2.0) if left untreated. Recommendations can be made to treat ewes in lower BCS and leave a proportion of the higher body condition sheep untreated in a targeted selective treatment programme, to provide a population of non-resistant worms to delay the development of resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

  19. The Time-domain Spectroscopic Survey: Target Selection for Repeat Spectroscopy

    Science.gov (United States)

    MacLeod, Chelsea L.; Green, Paul J.; Anderson, Scott F.; Eracleous, Michael; Ruan, John J.; Runnoe, Jessie; Nielsen Brandt, William; Badenes, Carles; Greene, Jenny; Morganson, Eric; Schmidt, Sarah J.; Schwope, Axel; Shen, Yue; Amaro, Rachael; Lebleu, Amy; Filiz Ak, Nurten; Grier, Catherine J.; Hoover, Daniel; McGraw, Sean M.; Dawson, Kyle; Hall, Patrick B.; Hawley, Suzanne L.; Mariappan, Vivek; Myers, Adam D.; Pâris, Isabelle; Schneider, Donald P.; Stassun, Keivan G.; Bershady, Matthew A.; Blanton, Michael R.; Seo, Hee-Jong; Tinker, Jeremy; Fernández-Trincado, J. G.; Chambers, Kenneth; Kaiser, Nick; Kudritzki, R.-P.; Magnier, Eugene; Metcalfe, Nigel; Waters, Chris Z.

    2018-01-01

    As astronomers increasingly exploit the information available in the time domain, spectroscopic variability in particular opens broad new channels of investigation. Here we describe the selection algorithms for all targets intended for repeat spectroscopy in the Time Domain Spectroscopic Survey (TDSS), part of the extended Baryon Oscillation Spectroscopic Survey within the Sloan Digital Sky Survey (SDSS)-IV. Also discussed are the scientific rationale and technical constraints leading to these target selections. The TDSS includes a large “repeat quasar spectroscopy” (RQS) program delivering ∼13,000 repeat spectra of confirmed SDSS quasars, and several smaller “few-epoch spectroscopy” (FES) programs targeting specific classes of quasars as well as stars. The RQS program aims to provide a large and diverse quasar data set for studying variations in quasar spectra on timescales of years, a comparison sample for the FES quasar programs, and an opportunity for discovering rare, serendipitous events. The FES programs cover a wide variety of phenomena in both quasars and stars. Quasar FES programs target broad absorption line quasars, high signal-to-noise ratio normal broad line quasars, quasars with double-peaked or very asymmetric broad emission line profiles, binary supermassive black hole candidates, and the most photometrically variable quasars. Strongly variable stars are also targeted for repeat spectroscopy, encompassing many types of eclipsing binary systems, and classical pulsators like RR Lyrae. Other stellar FES programs allow spectroscopic variability studies of active ultracool dwarf stars, dwarf carbon stars, and white dwarf/M dwarf spectroscopic binaries. We present example TDSS spectra and describe anticipated sample sizes and results.

  20. Mitochondrial targeted coenzyme Q, superoxide, and fuel selectivity in endothelial cells.

    Directory of Open Access Journals (Sweden)

    Brian D Fink

    Full Text Available Previously, we reported that the "antioxidant" compound "mitoQ" (mitochondrial-targeted ubiquinol/ubiquinone actually increased superoxide production by bovine aortic endothelial (BAE cell mitochondria incubated with complex I but not complex II substrates.To further define the site of action of the targeted coenzyme Q compound, we extended these studies to include different substrate and inhibitor conditions. In addition, we assessed the effects of mitoquinone on mitochondrial respiration, measured respiration and mitochondrial membrane potential in intact cells, and tested the intriguing hypothesis that mitoquinone might impart fuel selectivity in intact BAE cells. In mitochondria respiring on differing concentrations of complex I substrates, mitoquinone and rotenone had interactive effects on ROS consistent with redox cycling at multiple sites within complex I. Mitoquinone increased respiration in isolated mitochondria respiring on complex I but not complex II substrates. Mitoquinone also increased oxygen consumption by intact BAE cells. Moreover, when added to intact cells at 50 to 1000 nM, mitoquinone increased glucose oxidation and reduced fat oxidation, at doses that did not alter membrane potential or induce cell toxicity. Although high dose mitoquinone reduced mitochondrial membrane potential, the positively charged mitochondrial-targeted cation, decyltriphenylphosphonium (mitoquinone without the coenzyme Q moiety, decreased membrane potential more than mitoquinone, but did not alter fuel selectivity. Therefore, non-specific effects of the positive charge were not responsible and the quinone moiety is required for altered nutrient selectivity.In summary, the interactive effects of mitoquinone and rotenone are consistent with redox cycling at more than one site within complex I. In addition, mitoquinone has substrate dependent effects on mitochondrial respiration, increases repiration by intact cells, and alters fuel selectivity favoring

  1. Sequential Retraction Segregates SGN Processes during Target Selection in the Cochlea.

    Science.gov (United States)

    Druckenbrod, Noah R; Goodrich, Lisa V

    2015-12-09

    A hallmark of the nervous system is the presence of precise patterns of connections between different types of neurons. Many mechanisms can be used to establish specificity, including homophilic adhesion and synaptic refinement, but the range of strategies used across the nervous system remains unclear. To broaden the understanding of how neurons find their targets, we studied the developing murine cochlea, where two classes of spiral ganglion neurons (SGNs), type I and type II, navigate together to the sensory epithelium and then diverge to contact inner hair cells (IHCs) or outer hair cells (OHCs), respectively. Neurons with type I and type II morphologies are apparent before birth, suggesting that target selection might be accomplished by excluding type I processes from the OHC region. However, because type I processes appear to overshoot into type II territory postnatally, specificity may also depend on elimination of inappropriate synapses. To resolve these differences, we analyzed the morphology and dynamic behaviors of individual fibers and their branches as they interact with potential partners. We found that SGN processes continue to be segregated anatomically in the postnatal cochlea. Although type I-like fibers branched locally, few branches contacted OHCs, arguing against synaptic elimination. Instead, time-lapse imaging studies suggest a prominent role for retraction, first positioning processes to the appropriate region and then corralling branches during a subsequent period of exuberant growth and refinement. Thus, sequential stages of retraction can help to achieve target specificity, adding to the list of mechanisms available for sculpting neural circuits. During development, different types of neurons must form connections with specific synaptic targets, thereby creating the precise wiring diagram necessary for adult function. Although studies have revealed multiple mechanisms for target selection, we still know little about how different

  2. Antisense oligonucleotides targeting translation inhibitory elements in 5' UTRs can selectively increase protein levels.

    Science.gov (United States)

    Liang, Xue-Hai; Sun, Hong; Shen, Wen; Wang, Shiyu; Yao, Joyee; Migawa, Michael T; Bui, Huynh-Hoa; Damle, Sagar S; Riney, Stan; Graham, Mark J; Crooke, Rosanne M; Crooke, Stanley T

    2017-09-19

    A variety of diseases are caused by deficiencies in amounts or activity of key proteins. An approach that increases the amount of a specific protein might be of therapeutic benefit. We reasoned that translation could be specifically enhanced using trans-acting agents that counter the function of negative regulatory elements present in the 5' UTRs of some mRNAs. We recently showed that translation can be enhanced by antisense oligonucleotides (ASOs) that target upstream open reading frames. Here we report the amount of a protein can also be selectively increased using ASOs designed to hybridize to other translation inhibitory elements in 5' UTRs. Levels of human RNASEH1, LDLR, and ACP1 and of mouse ACP1 and ARF1 were increased up to 2.7-fold in different cell types and species upon treatment with chemically modified ASOs targeting 5' UTR inhibitory regions in the mRNAs encoding these proteins. The activities of ASOs in enhancing translation were sequence and position dependent and required helicase activity. The ASOs appear to improve the recruitment of translation initiation factors to the target mRNA. Importantly, ASOs targeting ACP1 mRNA significantly increased the level of ACP1 protein in mice, suggesting that this approach has therapeutic and research potentials. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  3. Automatic Speech-to-Background Ratio Selection to Maintain Speech Intelligibility in Broadcasts Using an Objective Intelligibility Metric

    Directory of Open Access Journals (Sweden)

    Yan Tang

    2018-01-01

    Full Text Available While mixing, sound producers and audio professionals empirically set the speech-to- background ratio (SBR based on rules of thumb and their own perception of sounds. There is no guarantee that the speech content will be intelligible for the general population consuming content over a wide variety of devices, however. In this study, an approach to automatically determine the appropriate SBR for a scene using an objective intelligibility metric is introduced. The model-estimated SBR needed for a preset minimum intelligibility level was compared to the listener-preferred SBR for a range of background sounds. It was found that an extra gain added to the model estimation is needed even for listeners with normal hearing. This gain is needed so an audio scene can be auditioned with comfort and without compromising the sound effects contributed by the background. When the background introduces little informational masking, the extra gain holds almost constant across the various background sounds. However, a larger gain is required for a background that induces informational masking, such as competing speech. The results from a final subjective rating study show that the model-estimated SBR with the additional gain, yields the same listening experience as the SBR preferred by listeners.

  4. Mature Epitope Density - A strategy for target selection based on immunoinformatics and exported prokaryotic proteins

    DEFF Research Database (Denmark)

    Santos, Anderson R; Pereira, Vanessa Bastos; Barbosa, Eudes

    2013-01-01

    . However, currently available tools do not account for the concentration of epitope products in the mature protein product and its relation to the reliability of target selection. RESULTS: We developed a computational strategy based on measuring the epitope's concentration in the mature protein, called...... Mature Epitope Density (MED). Our method, though simple, is capable of identifying promising vaccine targets. Our online software implementation provides a computationally light and reliable analysis of bacterial exoproteins and their potential for vaccines or diagnosis projects against pathogenic....... Half of the 60 proteins were classified as highest scored by the MED statistic, while the other half were classified as lowest scored. Among the lowest scored proteins, ~13% were confirmed as not related to antigenicity or not contributing to the bacterial pathogenicity, and 70% of the highest scored...

  5. Real-time target selection optimization to enhance alignment of gas chromatograms.

    Science.gov (United States)

    Dearing, Thomas I; Nadeau, Jeremy S; Rohrback, Brian G; Ramos, L Scott; Synovec, Robert E

    2011-01-15

    An improved method for real-time selection of the target for the alignment of gas chromatographic data is described. Further outlined is a simple method to determine the accuracy of the alignment procedure. The target selection method proposed uses a moving window of aligned chromatograms to generate a target, herein referred to as the window target method (WTM). The WTM was initially tested using a series of 100 simulated chromatograms, and additionally evaluated using a series of 55 diesel fuel gas chromatograms obtained with four fuel samples. The WTM was evaluated via a comparison to a related method (the nearest neighbor method (NNM)). The results using the WTM with simulated chromatograms showed a significant improvement in the correlation coefficient and the accuracy of alignment when compared to the alignments performed using the NNM. A significant improvement in real-time alignment accuracy, as assessed by a correlation coefficient metric, was achieved with the WTM (starting at ∼ 1.0 and declining to only ∼ 0.985 for the 100th sample), relative to the NNM (starting at ∼ 1.0 and declining to ∼ 0.4 for the 100th sample) for the simulated chromatogram study. The results determined when using the WTM with the diesel fuels also showed an improvement in correlation coefficient and accuracy of the within-class alignments as compared to the results obtained from the NNM. In practice, the WTM could be applied to the real-time analysis of process and feedstock industrial streams to enable real-time decision making from the more precisely aligned chromatographic data. Copyright © 2010 Elsevier B.V. All rights reserved.

  6. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    DEFF Research Database (Denmark)

    Lasko, Loren M; Jakob, Clarissa G; Edalji, Rohinton P

    2017-01-01

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved...... model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases....... also been implicated in human pathological conditions (including cancer). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products, bi-substrate analogues and the widely used small molecule C646, lack potency or selectivity. Here, we describe A-485, a potent...

  7. 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).

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

    International Nuclear Information System (INIS)

    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

    2016-01-01

    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. - Highlights: • Evodiamine selectively kills breast cancer stem like cells at G1 phase. • Evodiamine utilizes different mechanism of cell cycle modulation in CSLC and in bulk cancer cells. • Evodiamine activate the p53, p21 and Rb pathway.

  9. 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.

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

    Energy Technology Data Exchange (ETDEWEB)

    Han, Seula [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Woo, Jong Kyu [College of Pharmacy, Gachon University, Incheon (Korea, Republic of); Jung, Yuchae; Jeong, Dawoon; Kang, Minsook; Yoo, Young-Ji; Lee, Hani [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Oh, Seung Hyun [College of Pharmacy, Gachon University, Incheon (Korea, Republic of); Ryu, Jae-Ha [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of); Kim, Woo-Young, E-mail: wykim@sookmyung.ac.kr [The Research Center for Cell Fate Control, College of Pharmacy, Sookmyung Women' s University, Seoul (Korea, Republic of)

    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. - Highlights: • Evodiamine selectively kills breast cancer stem like cells at G1 phase. • Evodiamine utilizes different mechanism of cell cycle modulation in CSLC and in bulk cancer cells. • Evodiamine activate the p53, p21 and Rb pathway.

  11. Determination of perfluorobutane in rat blood by automatic headspace capillary gas chromatography and selected ion monitoring mass spectrometry.

    Science.gov (United States)

    Hvattum, E; Normann, P T; Oulie, I; Uran, S; Ringstad, O; Skotland, T

    2001-01-01

    A new contrast agent (Sonazoid; NC100100) for ultrasound imaging has been developed. It is an aqueous suspension of lipid stabilised perfluorobutane (PFB) gas microbubbles. An automatic headspace capillary gas-chromatographic mass spectrometric method using electron impact ionisation was developed for analysis of Sonazoid PFB in rat blood. The calibration standards were gaseous PFB dissolved in ethanol in the range of 0.5-5000 ng PFB. Fluorotrichloromethane (CFC 11) was used as an internal standard of the method and the MS detector was set to single ion monitoring of the base fragment ions of PFB (m/z 69 and 119) and CFC 11 (m/z 101). The calibration graph, made by plotting the peak area ratios of PFB (m/z 69) to CFC 11(m/z 101) against the amount of PFB, was fitted to a second-order polynomial equation with weighting 1/y2 and found to be reproducible. The limit of quantification of the method was set to 0.4 ng PFB. The between-day variation of the method was below 9.2% relative standard deviation (RSD) and the within-day variation of the method was below 7.6% RSD. The accuracy of the method, as compared to Coulter counter, was estimated by determination of PFB in samples where Sonazoid was added to saline and found to range from 91.5% to 105.2%. PFB, added as Sonazoid, was found to be stable for at least 7 months in rat blood samples when stored at -20 degrees C.

  12. Selective Targeting of SH2 Domain–Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies

    Energy Technology Data Exchange (ETDEWEB)

    Kükenshöner, Tim; Schmit, Nadine Eliane; Bouda, Emilie; Sha, Fern; Pojer, Florence; Koide, Akiko; Seeliger, Markus; Koide, Shohei; Hantschel, Oliver

    2017-05-01

    The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroup (Lck, Lyn, Blk, Hck). Interactome analysis of intracellularly expressed monobodies revealed that they bind SFKs but no other SH2-containing proteins. Three crystal structures of monobody–SH2 complexes unveiled different and only partly overlapping binding modes, which rationalized the observed selectivity and enabled structure-based mutagenesis to modulate inhibition mode and selectivity. In line with the critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor signaling, monobodies binding the Src and Hck SH2 domains selectively activated respective recombinant kinases, whereas an Lck SH2-binding monobody inhibited proximal signaling events downstream of the T-cell receptor complex. Our results show that SFK SH2 domains can be targeted with unprecedented potency and selectivity using monobodies. They are excellent tools for dissecting SFK functions in normal development and signaling and to interfere with aberrant SFK signaling networks in cancer cells.

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

    Energy Technology Data Exchange (ETDEWEB)

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

    2012-04-01

    Selected reaction monitoring (SRM)—also known as multiple reaction monitoring (MRM)—has emerged as a promising high-throughput targeted protein quantification technology for candidate biomarker verification and systems biology applications. A major bottleneck for current SRM technology, however, is insufficient sensitivity for e.g., detecting low-abundance biomarkers likely present at the pg/mL to low ng/mL range in human blood plasma or serum, or extremely low-abundance signaling proteins in the cells or tissues. Herein we review recent advances in methods and technologies, including front-end immunoaffinity depletion, fractionation, selective enrichment of target proteins/peptides or their posttranslational modifications (PTMs), as well as advances in MS instrumentation, which have significantly enhanced the overall sensitivity of SRM assays and enabled the detection of low-abundance proteins at low to sub- ng/mL level in human blood plasma or serum. General perspectives on the potential of achieving sufficient sensitivity for detection of pg/mL level proteins in plasma are also discussed.

  14. 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.

  15. Targeting Ras-Driven Cancer Cell Survival and Invasion through Selective Inhibition of DOCK1

    Directory of Open Access Journals (Sweden)

    Hirotada Tajiri

    2017-05-01

    Full Text Available Oncogenic Ras plays a key role in cancer initiation but also contributes to malignant phenotypes by stimulating nutrient uptake and promoting invasive migration. Because these latter cellular responses require Rac-mediated remodeling of the actin cytoskeleton, we hypothesized that molecules involved in Rac activation may be valuable targets for cancer therapy. We report that genetic inactivation of the Rac-specific guanine nucleotide exchange factor DOCK1 ablates both macropinocytosis-dependent nutrient uptake and cellular invasion in Ras-transformed cells. By screening chemical libraries, we have identified 1-(2-(3′-(trifluoromethyl-[1,1′-biphenyl]-4-yl-2-oxoethyl-5-pyrrolidinylsulfonyl-2(1H-pyridone (TBOPP as a selective inhibitor of DOCK1. TBOPP dampened DOCK1-mediated invasion, macropinocytosis, and survival under the condition of glutamine deprivation without impairing the biological functions of the closely related DOCK2 and DOCK5 proteins. Furthermore, TBOPP treatment suppressed cancer metastasis and growth in vivo in mice. Our results demonstrate that selective pharmacological inhibition of DOCK1 could be a therapeutic approach to target cancer cell survival and invasion.

  16. 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.

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

    Science.gov (United States)

    Wilson, Alexander D M; Brownscombe, Jacob W; Sullivan, Brittany; Jain-Schlaepfer, Sofia; Cooke, Steven J

    2015-01-01

    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.

  18. Selective apoptotic killing of malignant hemopoietic cells by antibody-targeted delivery of an amphipathic peptide.

    Science.gov (United States)

    Marks, Alexandra J; Cooper, Margaret S; Anderson, Robert J; Orchard, Kim H; Hale, Geoffrey; North, Janet M; Ganeshaguru, Kanagasabai; Steele, Andrew J; Mehta, Atul B; Lowdell, Mark W; Wickremasinghe, R Gitendra

    2005-03-15

    The alpha-helical amphipathic peptide D-(KLAKLAK)2 is toxic to eukaryotic cells if internalized by a suitable targeting mechanism. We have targeted this peptide to malignant hemopoietic cells via conjugation to monoclonal antibodies, which recognize lineage-specific cell surface molecules. An anti-CD19/peptide conjugate efficiently killed 3/3 B lymphoid lines. However, an anti-CD33/peptide conjugate was cytotoxic to only one of three CD33-positive myeloid leukemia lines. The IC50 towards susceptible lines were in the low nanomolar range. Conjugates were highly selective and did not kill cells that did not express the appropriate cell surface cognate of the antibody moiety. Anti-CD19/peptide conjugates efficiently killed cells from patients with chronic lymphocytic leukemia but anti-CD33/peptide reagents were less effective against fresh acute myeloid leukemia cells. We therefore suggest that amphipathic peptides may be of value as targeted therapeutic agents for the treatment of a subset of hematologic malignancies.

  19. 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.

  20. 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.

  1. An automatic optimum number of well-distributed ground control lines selection procedure based on genetic algorithm

    Science.gov (United States)

    Yavari, Somayeh; Valadan Zoej, Mohammad Javad; Salehi, Bahram

    2018-05-01

    The procedure of selecting an optimum number and best distribution of ground control information is important in order to reach accurate and robust registration results. This paper proposes a new general procedure based on Genetic Algorithm (GA) which is applicable for all kinds of features (point, line, and areal features). However, linear features due to their unique characteristics are of interest in this investigation. This method is called Optimum number of Well-Distributed ground control Information Selection (OWDIS) procedure. Using this method, a population of binary chromosomes is randomly initialized. The ones indicate the presence of a pair of conjugate lines as a GCL and zeros specify the absence. The chromosome length is considered equal to the number of all conjugate lines. For each chromosome, the unknown parameters of a proper mathematical model can be calculated using the selected GCLs (ones in each chromosome). Then, a limited number of Check Points (CPs) are used to evaluate the Root Mean Square Error (RMSE) of each chromosome as its fitness value. The procedure continues until reaching a stopping criterion. The number and position of ones in the best chromosome indicate the selected GCLs among all conjugate lines. To evaluate the proposed method, a GeoEye and an Ikonos Images are used over different areas of Iran. Comparing the obtained results by the proposed method in a traditional RFM with conventional methods that use all conjugate lines as GCLs shows five times the accuracy improvement (pixel level accuracy) as well as the strength of the proposed method. To prevent an over-parametrization error in a traditional RFM due to the selection of a high number of improper correlated terms, an optimized line-based RFM is also proposed. The results show the superiority of the combination of the proposed OWDIS method with an optimized line-based RFM in terms of increasing the accuracy to better than 0.7 pixel, reliability, and reducing systematic

  2. 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

  3. 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.

  4. 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

  5. Discovery of a selective catalytic p300/CBP inhibitor that targets lineage-specific tumours

    Energy Technology Data Exchange (ETDEWEB)

    Lasko, Loren M.; Jakob, Clarissa G.; Edalji, Rohinton P.; Qiu, Wei; Montgomery, Debra; Digiammarino, Enrico L.; Hansen, T. Matt; Risi, Roberto M.; Frey, Robin; Manaves, Vlasios; Shaw, Bailin; Algire, Mikkel; Hessler, Paul; Lam, Lloyd T.; Uziel, Tamar; Faivre, Emily; Ferguson, Debra; Buchanan, Fritz G.; Martin, Ruth L.; Torrent, Maricel; Chiang, Gary G.; Karukurichi, Kannan; Langston, J. William; Weinert, Brian T.; Choudhary, Chunaram; de Vries, Peter; Van Drie, John H.; McElligott, David; Kesicki, Ed; Marmorstein, Ronen; Sun, Chaohong; Cole, Philip A.; Rosenberg, Saul H.; Michaelides, Michael R.; Lai, Albert; Bromberg, Kenneth D. (AbbVie); (UCopenhagen); (Petra Pharma); (UPENN); (JHU); (Van Drie); (Faraday)

    2017-09-27

    The dynamic and reversible acetylation of proteins, catalysed by histone acetyltransferases (HATs) and histone deacetylases (HDACs), is a major epigenetic regulatory mechanism of gene transcription1 and is associated with multiple diseases. Histone deacetylase inhibitors are currently approved to treat certain cancers, but progress on the development of drug-like histone actyltransferase inhibitors has lagged behind2. The histone acetyltransferase paralogues p300 and CREB-binding protein (CBP) are key transcriptional co-activators that are essential for a multitude of cellular processes, and have also been implicated in human pathological conditions (including cancer3). Current inhibitors of the p300 and CBP histone acetyltransferase domains, including natural products4, bi-substrate analogues5 and the widely used small molecule C6466,7, lack potency or selectivity. Here, we describe A-485, a potent, selective and drug-like catalytic inhibitor of p300 and CBP. We present a high resolution (1.95 Å) co-crystal structure of a small molecule bound to the catalytic active site of p300 and demonstrate that A-485 competes with acetyl coenzyme A (acetyl-CoA). A-485 selectively inhibited proliferation in lineage-specific tumour types, including several haematological malignancies and androgen receptor-positive prostate cancer. A-485 inhibited the androgen receptor transcriptional program in both androgen-sensitive and castration-resistant prostate cancer and inhibited tumour growth in a castration-resistant xenograft model. These results demonstrate the feasibility of using small molecule inhibitors to selectively target the catalytic activity of histone acetyltransferases, which may provide effective treatments for transcriptional activator-driven malignancies and diseases.

  6. Note related to the elaboration of a coding by key sentences for the programming of a document automatic selection system

    International Nuclear Information System (INIS)

    Leroy, A.; Braffort, P.

    1959-01-01

    This note deals with the providing of CEA documentalists with a tool for coding studies. The authors first discuss issues related to code selection criteria (author classification, topic classification, and so on), and propose an overview and a discussion of linguistic models. They also comment how diagrams illustrating relationships between words are built up, and propose a diagram representation example which includes different concepts such as conditions, properties, object, tools or processes (for example hardness for a steel, batch processing for a condition, or sintering for a process), and also the introduction of negation. Then, the authors address how basic concepts can be highlighted, describe how key sentences can be built up, and propose an example analysis in the case of a published article dealing with nuclear reactors (in this case, the study of a liquid-metal neutron absorber for the control of a gas-cooled power reactor). Perspectives of evolution are finally discussed

  7. Ethyl Pyruvate: An Anti-Microbial Agent that Selectively Targets Pathobionts and Biofilms.

    Science.gov (United States)

    Debebe, Tewodros; Krüger, Monika; Huse, Klaus; Kacza, Johannes; Mühlberg, Katja; König, Brigitte; Birkenmeier, Gerd

    The microbiota has a strong influence on health and disease in humans. A causative shift favoring pathobionts is strongly linked to diseases. Therefore, anti-microbial agents selectively targeting potential pathogens as well as their biofilms are urgently demanded. Here we demonstrate the impact of ethyl pyruvate, so far known as ROS scavenger and anti-inflammatory agent, on planktonic microbes and biofilms. Ethyl pyruvate combats preferably the growth of pathobionts belonging to bacteria and fungi independent of the genera and prevailing drug resistance. Surprisingly, this anti-microbial agent preserves symbionts like Lactobacillus species. Moreover, ethyl pyruvate prevents the formation of biofilms and promotes matured biofilms dissolution. This potentially new anti-microbial and anti-biofilm agent could have a tremendous positive impact on human, veterinary medicine and technical industry as well.

  8. Ethyl Pyruvate: An Anti-Microbial Agent that Selectively Targets Pathobionts and Biofilms.

    Directory of Open Access Journals (Sweden)

    Tewodros Debebe

    Full Text Available The microbiota has a strong influence on health and disease in humans. A causative shift favoring pathobionts is strongly linked to diseases. Therefore, anti-microbial agents selectively targeting potential pathogens as well as their biofilms are urgently demanded. Here we demonstrate the impact of ethyl pyruvate, so far known as ROS scavenger and anti-inflammatory agent, on planktonic microbes and biofilms. Ethyl pyruvate combats preferably the growth of pathobionts belonging to bacteria and fungi independent of the genera and prevailing drug resistance. Surprisingly, this anti-microbial agent preserves symbionts like Lactobacillus species. Moreover, ethyl pyruvate prevents the formation of biofilms and promotes matured biofilms dissolution. This potentially new anti-microbial and anti-biofilm agent could have a tremendous positive impact on human, veterinary medicine and technical industry as well.

  9. Automatic Thermal Infrared Panoramic Imaging Sensor

    National Research Council Canada - National Science Library

    Gutin, Mikhail; Tsui, Eddy K; Gutin, Olga; Wang, Xu-Ming; Gutin, Alexey

    2006-01-01

    .... Automatic detection, location, and tracking of targets outside protected area ensures maximum protection and at the same time reduces the workload on personnel, increases reliability and confidence...

  10. NuMA is required for the selective induction of p53 target genes.

    Science.gov (United States)

    Ohata, Hirokazu; Miyazaki, Makoto; Otomo, Ryo; Matsushima-Hibiya, Yuko; Otsubo, Chihiro; Nagase, Takahiro; Arakawa, Hirofumi; Yokota, Jun; Nakagama, Hitoshi; Taya, Yoichi; Enari, Masato

    2013-06-01

    The p53 tumor suppressor protein is a transcription factor controlling various outcomes, such as growth arrest and apoptosis, through the regulation of different sets of target genes. The nuclear mitotic apparatus protein (NuMA) plays important roles in spindle pole organization during mitosis and in chromatin regulation in the nucleus during interphase. Although NuMA has been shown to colocalize with several nuclear proteins, including high-mobility-group proteins I and Y and GAS41, the role of NuMA during interphase remains unclear. Here we report that NuMA binds to p53 to modulate p53-mediated transcription. Acute and partial ablation of NuMA attenuates the induction of the proarrested p21 gene following DNA damage, subsequently causing impaired cell cycle arrest. Interestingly, NuMA knockdown had little effect on the induction of the p53-dependent proapoptotic PUMA gene. Furthermore, NuMA is required for the recruitment of cyclin-dependent kinase 8 (Cdk8), a component of the Mediator complex and a promoter of p53-mediated p21 gene function. These data demonstrate that NuMA is critical for the target selectivity of p53-mediated transcription.

  11. Non-invasive brain stimulation targeting the right fusiform gyrus selectively increases working memory for faces.

    Science.gov (United States)

    Brunyé, Tad T; Moran, Joseph M; Holmes, Amanda; Mahoney, Caroline R; Taylor, Holly A

    2017-04-01

    The human extrastriate cortex contains a region critically involved in face detection and memory, the right fusiform gyrus. The present study evaluated whether transcranial direct current stimulation (tDCS) targeting this anatomical region would selectively influence memory for faces versus non-face objects (houses). Anodal tDCS targeted the right fusiform gyrus (Brodmann's Area 37), with the anode at electrode site PO10, and cathode at FP2. Two stimulation conditions were compared in a repeated-measures design: 0.5mA versus 1.5mA intensity; a separate control group received no stimulation. Participants completed a working memory task for face and house stimuli, varying in memory load from 1 to 4 items. Individual differences measures assessed trait-based differences in facial recognition skills. Results showed 1.5mA intensity stimulation (versus 0.5mA and control) increased performance at high memory loads, but only with faces. Lower overall working memory capacity predicted a positive impact of tDCS. Results provide support for the notion of functional specialization of the right fusiform regions for maintaining face (but not non-face object) stimuli in working memory, and further suggest that low intensity electrical stimulation of this region may enhance demanding face working memory performance particularly in those with relatively poor baseline working memory skills. Published by Elsevier Inc.

  12. First report of in vitro selection of RNA aptamers targeted to recombinant Loxosceles laeta spider toxins.

    Science.gov (United States)

    Sapag, Amalia; Salinas-Luypaert, Catalina; Constenla-Muñoz, Carlos

    2014-03-26

    Loxoscelism is the envenomation caused by the bite of Loxosceles spp. spiders. It entails severe necrotizing skin lesions, sometimes accompanied by systemic reactions and even death. There are no diagnostic means and treatment is mostly palliative. The main toxin, found in several isoforms in the venom, is sphingomyelinase D (SMD), a phospholipase that has been used to generate antibodies intended for medical applications. Nucleic acid aptamers are a promising alternative to antibodies. Aptamers may be isolated from a combinatorial mixture of oligonucleotides by iterative selection of those that bind to the target. In this work, two Loxosceles laeta SMD isoforms, Ll1 and Ll2, were produced in bacteria and used as targets with the aim of identifying RNA aptamers that inhibit sphingomyelinase activity. Six RNA aptamers capable of eliciting partial but statistically significant inhibitions of the sphingomyelinase activity of recombinant SMD-Ll1 and SMD-Ll2 were obtained: four aptamers exert ~17% inhibition of SMD-Ll1, while two aptamers result in ~25% inhibition of SMD-Ll2 and ~18% cross inhibition of SMD-Ll1. This work is the first attempt to obtain aptamers with therapeutic and diagnostic potential for loxoscelism and provides an initial platform to undertake the development of novel anti Loxosceles venom agents.

  13. First report of in vitro selection of RNA aptamers targeted to recombinant Loxosceles laeta spider toxins

    Directory of Open Access Journals (Sweden)

    Amalia Sapag

    2014-01-01

    Full Text Available BACKGROUND: Loxoscelism is the envenomation caused by the bite of Loxosceles spp. spiders. It entails severe necrotizing skin lesions, sometimes accompanied by systemic reactions and even death. There are no diagnostic means and treatment is mostly palliative. The main toxin, found in several isoforms in the venom, is sphingomyelinase D (SMD, a phospholipase that has been used to generate antibodies intended for medical applications. Nucleic acid aptamers are a promising alternative to antibodies. Aptamers may be isolated from a combinatorial mixture of oligonucleotides by iterative selection of those that bind to the target. In this work, two Loxosceles laeta SMD isoforms, Ll1 and Ll2, were produced in bacteria and used as targets with the aim of identifying RNA aptamers that inhibit sphingomyelinase activity. RESULTS: Six RNA aptamers capable of eliciting partial but statistically significant inhibitions of the sphingomyelinase activity of recombinant SMD-Ll1 and SMD-Ll2 were obtained: four aptamers exert ~17% inhibition of SMD-Ll1, while two aptamers result in ~25% inhibition of SMD-Ll2 and ~18% cross inhibition of SMD-Ll1. CONCLUSIONS: This work is the first attempt to obtain aptamers with therapeutic and diagnostic potential for loxoscelism and provides an initial platform to undertake the development of novel anti Loxoscelesvenom agents.

  14. Bombesin peptide antagonist for target-selective delivery of liposomal doxorubicin on cancer cells.

    Science.gov (United States)

    Accardo, Antonella; Mansi, Rosalba; Salzano, Giuseppina; Morisco, Anna; Aurilio, Michela; Parisi, Antonio; Maione, Francesco; Cicala, Carla; Ziaco, Barbara; Tesauro, Diego; Aloj, Luigi; De Rosa, Giuseppe; Morelli, Giancarlo

    2012-11-21

    Purpose: This study addresses novel peptide modified liposomal doxorubicin to specifically target tissues overexpressing bombesin (BN) receptors. Methods: DOTA-(AEEA)(2)-peptides containing the [7-14]bombesin and the new BN-AA1 sequence have been synthesized to compare their binding properties and in serum stabilities. The amphiphilic peptide derivative (MonY-BN-AA1) containing BN-AA1, a hydrophobic moiety, polyethylenglycole (PEG), and diethylenetriaminepentaacetate (DTPA), has been synthesized. Liposomes have been obtained by mixing of MonY-BN-AA1 with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). Results: Both (111)In labeled peptide derivatives present nanomolar Kd to PC-3 cells. (177)Lu labeled peptide DOTA-(AEEA)(2)-BN-AA1 is very stable (half-life 414.1 h), while DOTA-(AEEA)(2)-BN, shows a half-life of 15.5 h. In vivo studies on the therapeutic efficacy of DSPC/MonY-BN-AA1/Dox in comparison to DSPC/MonY-BN/Dox, were performed in PC-3 xenograft bearing mice. Both formulations showed similar tumor growth inhibition (TGI) compared to control animals treated with non-targeted DSPC/Dox liposomes or saline solution. For DSPC/MonY-BN-AA1/Dox the maximum effect was observed 19 days after treatment. Conclusions: DSPC/MonY-BN-AA1/Dox nanovectors confirm the ability to selectively target and provide therapeutic efficacy in mice. The lack of receptor activation and possible acute biological side effects provided by using the AA1 antagonist bombesin sequence should provide safe working conditions for further development of this class of drug delivery vehicles.

  15. The Breakthrough Listen Search for Intelligent Life: Target Selection of Nearby Stars and Galaxies

    Science.gov (United States)

    Isaacson, Howard; Siemion, Andrew P. V.; Marcy, Geoffrey W.; Lebofsky, Matt; Price, Danny C.; MacMahon, David; Croft, Steve; DeBoer, David; Hickish, Jack; Werthimer, Dan; Sheikh, Sofia; Hellbourg, Greg; Enriquez, J. Emilio

    2017-05-01

    We present the target selection for the Breakthrough Listen search for extraterrestrial intelligence during the first year of observations at the Green Bank Telescope, Parkes Telescope, and Automated Planet Finder. On the way to observing 1,000,000 nearby stars in search of technological signals, we present three main sets of objects we plan to observe in addition to a smaller sample of exotica. We chose the 60 nearest stars, all within 5.1 pc from the Sun. Such nearby stars offer the potential to observe faint radio signals from transmitters that have a power similar to those on Earth. We add a list of 1649 stars drawn from the Hipparcos catalog that span the Hertzprung-Russell diagram, including all spectral types along the main sequence, subgiants, and giant stars. This sample offers diversity and inclusion of all stellar types, but with thoughtful limits and due attention to main sequence stars. Our targets also include 123 nearby galaxies composed of a “morphological-type-complete” sample of the nearest spirals, ellipticals, dwarf spherioidals, and irregulars. While their great distances hamper the detection of technological electromagnetic radiation, galaxies offer the opportunity to observe billions of stars simultaneously and to sample the bright end of the technological luminosity function. We will also use the Green Bank and Parkes telescopes to survey the plane and central bulge of the Milky Way. Finally, the complete target list includes several classes of exotica, including white dwarfs, brown dwarfs, black holes, neutron stars, and asteroids in our solar system.

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

    Science.gov (United States)

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

    2014-12-01

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

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

    Directory of Open Access Journals (Sweden)

    Joubert Fourie

    2008-05-01

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

  18. 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.

  19. β-escin selectively targets the glioblastoma-initiating cell population and reduces cell viability.

    Science.gov (United States)

    Harford-Wright, Elizabeth; Bidère, Nicolas; Gavard, Julie

    2016-10-11

    Glioblastoma multiforme (GBM) is a highly aggressive tumour of the central nervous system and is associated with an extremely poor prognosis. Within GBM exists a subpopulation of cells, glioblastoma-initiating cells (GIC), which possess the characteristics of progenitor cells, have the ability to initiate tumour growth and resist to current treatment strategies. We aimed at identifying novel specific inhibitors of GIC expansion through use of a large-scale chemical screen of approved small molecules. Here, we report the identification of the natural compound β-escin as a selective inhibitor of GIC viability. Indeed, β-escin was significantly cytotoxic in nine patient-derived GIC, whilst exhibiting no substantial effect on the other human cancer or control cell lines tested. In addition, β-escin was more effective at reducing GIC growth than current clinically used cytotoxic agents. We further show that β-escin triggers caspase-dependent cell death combined with a loss of stemness properties. However, blocking apoptosis could not rescue the β-escin-induced reduction in sphere formation or stemness marker activity, indicating that β-escin directly modifies the stem identity of GIC, independent of the induction of cell death. Thus, this study has repositioned β-escin as a promising potential candidate to selectively target the aggressive population of initiating cells within GBM.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Johannes Krisam

    2015-05-01

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

  2. Identification of genomic variants putatively targeted by selection during dog domestication.

    Science.gov (United States)

    Cagan, Alex; Blass, Torsten

    2016-01-12

    Dogs [Canis lupus familiaris] were the first animal species to be domesticated and continue to occupy an important place in human societies. Recent studies have begun to reveal when and where dog domestication occurred. While much progress has been made in identifying the genetic basis of phenotypic differences between dog breeds we still know relatively little about the genetic changes underlying the phenotypes that differentiate all dogs from their wild progenitors, wolves [Canis lupus]. In particular, dogs generally show reduced aggression and fear towards humans compared to wolves. Therefore, selection for tameness was likely a necessary prerequisite for dog domestication. With the increasing availability of whole-genome sequence data it is possible to try and directly identify the genetic variants contributing to the phenotypic differences between dogs and wolves. We analyse the largest available database of genome-wide polymorphism data in a global sample of dogs 69 and wolves 7. We perform a scan to identify regions of the genome that are highly differentiated between dogs and wolves. We identify putatively functional genomic variants that are segregating or at high frequency [> = 0.75 Fst] for alternative alleles between dogs and wolves. A biological pathways analysis of the genes containing these variants suggests that there has been selection on the 'adrenaline and noradrenaline biosynthesis pathway', well known for its involvement in the fight-or-flight response. We identify 11 genes with putatively functional variants fixed for alternative alleles between dogs and wolves. The segregating variants in these genes are strong candidates for having been targets of selection during early dog domestication. We present the first genome-wide analysis of the different categories of putatively functional variants that are fixed or segregating at high frequency between a global sampling of dogs and wolves. We find evidence that selection has been strongest

  3. Virotherapy targeting cyclin E overexpression in tumors with adenovirus-enhanced cancer-selective promoter.

    Science.gov (United States)

    Cheng, Pei-Hsin; Rao, Xiao-Mei; Duan, Xiaoxian; Li, Xiao-Feng; Egger, Michael E; McMasters, Kelly M; Zhou, H Sam

    2015-02-01

    Oncolytic virotherapy can selectively destroy cancer cells and is a potential approach in cancer treatment. A strategy to increase tumor-specific selectivity is to control the expression of a key regulatory viral gene with a tumor-specific promoter. We have previously found that cyclin E expression is augmented in cancer cells after adenovirus (Ad) infection. Thus, the cyclin E promoter that is further activated by Ad in cancer cells may have unique properties for enhancing oncolytic viral replication. We have shown that high levels of viral E1a gene expression are achieved in cancer cells infected with Ad-cycE, in which the endogenous Ad E1a promoter was replaced with the cyclin E promoter. Ad-cycE shows markedly selective oncolytic efficacy in vitro and destroys various types of cancer cells, including those resistant to ONYX-015/dl1520. Furthermore, Ad-cycE shows a strong capacity to repress A549 xenograft tumor growth in nude mice and significantly prolongs survival. This study suggests the potential of Ad-cycE in cancer therapy and indicates the advantages of using promoters that can be upregulated by virus infection in cancer cells in development of oncolytic viruses. Key messages: Cyclin E promoter activity is high in cancer cells and enhanced by adenovirus infection. Cyclin E promoter is used to control the E1a gene of a tumor-specific oncolytic adenovirus. Ad-cycE efficiently targets cancer cells and induces oncolysis. Ad-cycE significantly repressed xenograft tumor and prolonged survival.

  4. PEG-functionalized microparticles selectively target inflamed mucosa in inflammatory bowel disease.

    Science.gov (United States)

    Lautenschläger, Christian; Schmidt, Carsten; Lehr, Claus-Michael; Fischer, Dagmar; Stallmach, Andreas

    2013-11-01

    The systemic therapy of inflammatory bowel diseases (IBD) by oral administration of anti-inflammatory and immunosuppressive agents is characterized by an increased probability of adverse drug reactions. A successful treatment with a simultaneous reduction in adverse events may be achieved by the administration of micro- and nanosized targeted drug delivery systems, which accumulate selectively in inflamed mucosal areas without systemic absorption. We described in a first in vivo study in IBD patients a significantly enhanced, but minor accumulation of non-functionalized poly(lactic-co-glycolic acid) (PLGA) microparticles in ulcerous lesions very recently. The aim of this study was therefore the assessment of an increased targeting potential of different non-, chitosan- and polyethylene glycol (PEG)-functionalized PLGA micro- and nanoparticles to inflamed intestinal mucosa compared to healthy mucosa. For the quantification of nano- and microparticles, fluoresceinamine-labeled-PLGA was synthesized by carbodiimide reaction. Fluorescent chitosan-, PEG-, and non-functionalized PLGA micro- and nanoparticles with mean hydrodynamic diameters of 3000 nm and 300 nm were prepared by solvent evaporation technique. The targeting efficiencies in terms of particle translocation and deposition were investigated in Ussing chamber experiments. Healthy and inflamed macrobiopsies were received from routine endoscopic examinations of patients with IBD as well as control patients. One-hundred and one Ussing chamber experiments of patients with IBD (Crohn's disease: n=7 and ulcerative colitis: n=9) as well as healthy control patients (n=5) were performed. Histomorphological and electrophysiological investigations of inflamed mucosal tissues confirmed a significant alteration of mucosal barrier integrity in IBD patients (TER: healthy: 34.1 Ω cm(2); inflamed: 21.6 Ωc m(2); p=0.034). In summary, nanoparticles showed an increased translocation and deposition compared to microparticles in

  5. 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.)

  6. Implementation and flight tests for the Digital Integrated Automatic Landing System (DIALS). Part 1: Flight software equations, flight test description and selected flight test data

    Science.gov (United States)

    Hueschen, R. M.

    1986-01-01

    Five flight tests of the Digital Automated Landing System (DIALS) were conducted on the Advanced Transport Operating Systems (ATOPS) Transportation Research Vehicle (TSRV) -- a modified Boeing 737 aircraft for advanced controls and displays research. These flight tests were conducted at NASA's Wallops Flight Center using the microwave landing system (MLS) installation on runway 22. This report describes the flight software equations of the DIALS which was designed using modern control theory direct-digital design methods and employed a constant gain Kalman filter. Selected flight test performance data is presented for localizer (runway centerline) capture and track at various intercept angles, for glideslope capture and track of 3, 4.5, and 5 degree glideslopes, for the decrab maneuver, and for the flare maneuver. Data is also presented to illustrate the system performance in the presence of cross, gust, and shear winds. The mean and standard deviation of the peak position errors for localizer capture were, respectively, 24 feet and 26 feet. For mild wind conditions, glideslope and localizer tracking position errors did not exceed, respectively, 5 and 20 feet. For gusty wind conditions (8 to 10 knots), these errors were, respectively, 10 and 30 feet. Ten hands off automatic lands were performed. The standard deviation of the touchdown position and velocity errors from the mean values were, respectively, 244 feet and 0.7 feet/sec.

  7. GLUT1-mediated selective tumor targeting with fluorine containing platinum(II) glycoconjugates.

    Science.gov (United States)

    Liu, Ran; Fu, Zheng; Zhao, Meng; Gao, Xiangqian; Li, Hong; Mi, Qian; Liu, Pengxing; Yang, Jinna; Yao, Zhi; Gao, Qingzhi

    2017-06-13

    Increased glycolysis and overexpression of glucose transporters (GLUTs) are physiological characteristics of human malignancies. Based on the so-called Warburg effect, 18flurodeoxyglucose-positron emission tomography (FDG-PET) has successfully developed as clinical modality for the diagnosis and staging of many cancers. To leverage this glucose transporter mediated metabolic disparity between normal and malignant cells, in the current report, we focus on the fluorine substituted series of glucose, mannose and galactose-conjugated (trans-R,R-cyclohexane-1,2-diamine)-2-flouromalonato-platinum(II) complexes for a comprehensive evaluation on their selective tumor targeting. Besides highly improved water solubility, these sugar-conjugates presented improved cytotoxicity than oxaliplatin in glucose tranporters (GLUTs) overexpressing cancer cell lines and exhibited no cross-resistance to cisplatin. For the highly water soluble glucose-conjugated complex (5a), two novel in vivo assessments were conducted and the results revealed that 5a was more efficacious at a lower equitoxic dose (70% MTD) than oxaliplatin (100% MTD) in HT29 xenograft model, and it was significantly more potent than oxaliplatin in leukemia-bearing DBA/2 mice as well even at equimolar dose levels (18% vs 90% MTD). GLUT inhibitor mediated cell viability analysis, GLUT1 knockdown cell line-based cytotoxicity evaluation, and platinum accumulation study demonstrated that the cellular uptake of the sugar-conjugates was regulated by GLUT1. The higher intrinsic DNA reactivity of the sugar-conjugates was confirmed by kinetic study of platinum(II)-guanosine adduct formation. The mechanistic origin of the antitumor effect of the fluorine complexes was found to be forming the bifunctional Pt-guanine-guanine (Pt-GG) intrastrand cross-links with DNA. The results provide a rationale for Warburg effect targeted anticancer drug design.

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

    International Nuclear Information System (INIS)

    Dwivedy, K.K.; Sinha, K.K.

    1997-01-01

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

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

    Directory of Open Access Journals (Sweden)

    Ji She

    2016-12-01

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

  10. Body composition estimation from selected slices: equations computed from a new semi-automatic thresholding method developed on whole-body CT scans

    Directory of Open Access Journals (Sweden)

    Alizé Lacoste Jeanson

    2017-05-01

    Full Text Available Background Estimating volumes and masses of total body components is important for the study and treatment monitoring of nutrition and nutrition-related disorders, cancer, joint replacement, energy-expenditure and exercise physiology. While several equations have been offered for estimating total body components from MRI slices, no reliable and tested method exists for CT scans. For the first time, body composition data was derived from 41 high-resolution whole-body CT scans. From these data, we defined equations for estimating volumes and masses of total body AT and LT from corresponding tissue areas measured in selected CT scan slices. Methods We present a new semi-automatic approach to defining the density cutoff between adipose tissue (AT and lean tissue (LT in such material. An intra-class correlation coefficient (ICC was used to validate the method. The equations for estimating the whole-body composition volume and mass from areas measured in selected slices were modeled with ordinary least squares (OLS linear regressions and support vector machine regression (SVMR. Results and Discussion The best predictive equation for total body AT volume was based on the AT area of a single slice located between the 4th and 5th lumbar vertebrae (L4-L5 and produced lower prediction errors (|PE| = 1.86 liters, %PE = 8.77 than previous equations also based on CT scans. The LT area of the mid-thigh provided the lowest prediction errors (|PE| = 2.52 liters, %PE = 7.08 for estimating whole-body LT volume. We also present equations to predict total body AT and LT masses from a slice located at L4-L5 that resulted in reduced error compared with the previously published equations based on CT scans. The multislice SVMR predictor gave the theoretical upper limit for prediction precision of volumes and cross-validated the results.

  11. Using Deep Learning for Targeted Data Selection, Improving Satellite Observation Utilization for Model Initialization

    Science.gov (United States)

    Lee, Y. J.; Bonfanti, C. E.; Trailovic, L.; Etherton, B.; Govett, M.; Stewart, J.

    2017-12-01

    At present, a fraction of all satellite observations are ultimately used for model assimilation. The satellite data assimilation process is computationally expensive and data are often reduced in resolution to allow timely incorporation into the forecast. This problem is only exacerbated by the recent launch of Geostationary Operational Environmental Satellite (GOES)-16 satellite and future satellites providing several order of magnitude increase in data volume. At the NOAA Earth System Research Laboratory (ESRL) we are researching the use of machine learning the improve the initial selection of satellite data to be used in the model assimilation process. In particular, we are investigating the use of deep learning. Deep learning is being applied to many image processing and computer vision problems with great success. Through our research, we are using convolutional neural network to find and mark regions of interest (ROI) to lead to intelligent extraction of observations from satellite observation systems. These targeted observations will be used to improve the quality of data selected for model assimilation and ultimately improve the impact of satellite data on weather forecasts. Our preliminary efforts to identify the ROI's are focused in two areas: applying and comparing state-of-art convolutional neural network models using the analysis data from the National Center for Environmental Prediction (NCEP) Global Forecast System (GFS) weather model, and using these results as a starting point to optimize convolution neural network model for pattern recognition on the higher resolution water vapor data from GOES-WEST and other satellite. This presentation will provide an introduction to our convolutional neural network model to identify and process these ROI's, along with the challenges of data preparation, training the model, and parameter optimization.

  12. 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

    2017-12-01

    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.

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

    Science.gov (United States)

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

    2006-01-10

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

  14. A covalent PIN1 inhibitor selectively targets cancer cells by a dual mechanism of action

    Science.gov (United States)

    Campaner, Elena; Rustighi, Alessandra; Zannini, Alessandro; Cristiani, Alberto; Piazza, Silvano; Ciani, Yari; Kalid, Ori; Golan, Gali; Baloglu, Erkan; Shacham, Sharon; Valsasina, Barbara; Cucchi, Ulisse; Pippione, Agnese Chiara; Lolli, Marco Lucio; Giabbai, Barbara; Storici, Paola; Carloni, Paolo; Rossetti, Giulia; Benvenuti, Federica; Bello, Ezia; D'Incalci, Maurizio; Cappuzzello, Elisa; Rosato, Antonio; Del Sal, Giannino

    2017-06-01

    The prolyl isomerase PIN1, a critical modifier of multiple signalling pathways, is overexpressed in the majority of cancers and its activity strongly contributes to tumour initiation and progression. Inactivation of PIN1 function conversely curbs tumour growth and cancer stem cell expansion, restores chemosensitivity and blocks metastatic spread, thus providing the rationale for a therapeutic strategy based on PIN1 inhibition. Notwithstanding, potent PIN1 inhibitors are still missing from the arsenal of anti-cancer drugs. By a mechanism-based screening, we have identified a novel covalent PIN1 inhibitor, KPT-6566, able to selectively inhibit PIN1 and target it for degradation. We demonstrate that KPT-6566 covalently binds to the catalytic site of PIN1. This interaction results in the release of a quinone-mimicking drug that generates reactive oxygen species and DNA damage, inducing cell death specifically in cancer cells. Accordingly, KPT-6566 treatment impairs PIN1-dependent cancer phenotypes in vitro and growth of lung metastasis in vivo.

  15. Vitamin C selectively kills KRAS and BRAF mutant colorectal cancer cells by targeting GAPDH.

    Science.gov (United States)

    Yun, Jihye; Mullarky, Edouard; Lu, Changyuan; Bosch, Kaitlyn N; Kavalier, Adam; Rivera, Keith; Roper, Jatin; Chio, Iok In Christine; Giannopoulou, Eugenia G; Rago, Carlo; Muley, Ashlesha; Asara, John M; Paik, Jihye; Elemento, Olivier; Chen, Zhengming; Pappin, Darryl J; Dow, Lukas E; Papadopoulos, Nickolas; Gross, Steven S; Cantley, Lewis C

    2015-12-11

    More than half of human colorectal cancers (CRCs) carry either KRAS or BRAF mutations and are often refractory to approved targeted therapies. We found that cultured human CRC cells harboring KRAS or BRAF mutations are selectively killed when exposed to high levels of vitamin C. This effect is due to increased uptake of the oxidized form of vitamin C, dehydroascorbate (DHA), via the GLUT1 glucose transporter. Increased DHA uptake causes oxidative stress as intracellular DHA is reduced to vitamin C, depleting glutathione. Thus, reactive oxygen species accumulate and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH). Inhibition of GAPDH in highly glycolytic KRAS or BRAF mutant cells leads to an energetic crisis and cell death not seen in KRAS and BRAF wild-type cells. High-dose vitamin C impairs tumor growth in Apc/Kras(G12D) mutant mice. These results provide a mechanistic rationale for exploring the therapeutic use of vitamin C for CRCs with KRAS or BRAF mutations. Copyright © 2015, American Association for the Advancement of Science.

  16. 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.

  17. A Predictive Model for Selective Targeting of the Warburg Effect through GAPDH Inhibition with a Natural Product.

    Science.gov (United States)

    Liberti, Maria V; Dai, Ziwei; Wardell, Suzanne E; Baccile, Joshua A; Liu, Xiaojing; Gao, Xia; Baldi, Robert; Mehrmohamadi, Mahya; Johnson, Marc O; Madhukar, Neel S; Shestov, Alexander A; Chio, Iok I Christine; Elemento, Olivier; Rathmell, Jeffrey C; Schroeder, Frank C; McDonnell, Donald P; Locasale, Jason W

    2017-10-03

    Targeted cancer therapies that use genetics are successful, but principles for selectively targeting tumor metabolism that is also dependent on the environment remain unknown. We now show that differences in rate-controlling enzymes during the Warburg effect (WE), the most prominent hallmark of cancer cell metabolism, can be used to predict a response to targeting glucose metabolism. We establish a natural product, koningic acid (KA), to be a selective inhibitor of GAPDH, an enzyme we characterize to have differential control properties over metabolism during the WE. With machine learning and integrated pharmacogenomics and metabolomics, we demonstrate that KA efficacy is not determined by the status of individual genes, but by the quantitative extent of the WE, leading to a therapeutic window in vivo. Thus, the basis of targeting the WE can be encoded by molecular principles that extend beyond the status of individual genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  18. [Development of a Software for Automatically Generated Contours in Eclipse TPS].

    Science.gov (United States)

    Xie, Zhao; Hu, Jinyou; Zou, Lian; Zhang, Weisha; Zou, Yuxin; Luo, Kelin; Liu, Xiangxiang; Yu, Luxin

    2015-03-01

    The automatic generation of planning targets and auxiliary contours have achieved in Eclipse TPS 11.0. The scripting language autohotkey was used to develop a software for automatically generated contours in Eclipse TPS. This software is named Contour Auto Margin (CAM), which is composed of operational functions of contours, script generated visualization and script file operations. RESULTS Ten cases in different cancers have separately selected, in Eclipse TPS 11.0 scripts generated by the software could not only automatically generate contours but also do contour post-processing. For different cancers, there was no difference between automatically generated contours and manually created contours. The CAM is a user-friendly and powerful software, and can automatically generated contours fast in Eclipse TPS 11.0. With the help of CAM, it greatly save plan preparation time and improve working efficiency of radiation therapy physicists.

  19. 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

  20. 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

  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. Attention Blinks for Selection, Not Perception or Memory: Reading Sentences and Reporting Targets

    Science.gov (United States)

    Potter, Mary C.; Wyble, Brad; Olejarczyk, Jennifer

    2011-01-01

    In whole report, a sentence presented sequentially at the rate of about 10 words/s can be recalled accurately, whereas if the task is to report only two target words (e.g., red words), the second target suffers an attentional blink if it appears shortly after the first target. If these two tasks are carried out simultaneously, is there an…

  3. 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.

  4. On the development of conjunctival hyperemia computer-assisted diagnosis tools: Influence of feature selection and class imbalance in automatic gradings.

    Science.gov (United States)

    Sánchez Brea, María Luisa; Barreira Rodríguez, Noelia; Sánchez Maroño, Noelia; Mosquera González, Antonio; García-Resúa, Carlos; Giráldez Fernández, María Jesús

    2016-07-01

    The sudden increase of blood flow in the bulbar conjunctiva, known as hyperemia, is associated to a red hue of variable intensity. Experts measure hyperemia using levels in a grading scale, a procedure that is subjective, non-repeatable and time consuming, thus creating a need for its automatisation. However, the task is far from straightforward due to data issues such as class imbalance or correlated features. In this paper, we study the specific features of hyperemia and propose various approaches to address these problems in the context of an automatic framework for hyperemia grading. Oversampling, undersampling and SMOTE approaches were applied in order to tackle the problem of class imbalance. 25 features were computed for each image and regression methods were then used to transform them into a value on the grading scale. The values and relationships among features and experts' values were analysed, and five feature selection techniques were subsequently studied. The lowest mean square error (MSE) for the regression systems trained with individual features is below 0.1 for both scales. Multi-layer perceptron (MLP) obtains the best values, but is less consistent than the random forest (RF) method. When all features are combined, the best results for both scales are achieved with MLP. Correlation based feature selection (CFS) and M5 provide the best results, MSE=0.108 and MSE=0.061 respectively. Finally, the class imbalance problem is minimised with the SMOTE approach for both scales (MSElearning methods are able to perform an objective assessment of hyperemia grading, removing both intra- and inter-expert subjectivity while providing a gain in computation time. SMOTE and oversampling approaches minimise the class imbalance problem, while feature selection reduces the number of features from 25 to 3-5 without worsening the MSE. As the differences between the system and a human expert are similar to the differences between experts, we can therefore conclude that

  5. 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.

  6. Selecting Tumor-Specific Molecular Targets in Pancreatic Adenocarcinoma: Paving the Way for Image-Guided Pancreatic Surgery.

    Science.gov (United States)

    de Geus, Susanna W L; Boogerd, Leonora S F; Swijnenburg, Rutger-Jan; Mieog, J Sven D; Tummers, Willemieke S F J; Prevoo, Hendrica A J M; Sier, Cornelis F M; Morreau, Hans; Bonsing, Bert A; van de Velde, Cornelis J H; Vahrmeijer, Alexander L; Kuppen, Peter J K

    2016-12-01

    The purpose of this study was to identify suitable molecular targets for tumor-specific imaging of pancreatic adenocarcinoma. The expression of eight potential imaging targets was assessed by the target selection criteria (TASC)-score and immunohistochemical analysis in normal pancreatic tissue (n = 9), pancreatic (n = 137), and periampullary (n = 28) adenocarcinoma. Integrin α v β 6 , carcinoembryonic antigen (CEA), epithelial growth factor receptor (EGFR), and urokinase plasminogen activator receptor (uPAR) showed a significantly higher (all p < 0.001) expression in pancreatic adenocarcinoma compared to normal pancreatic tissue and were confirmed by the TASC score as promising imaging targets. Furthermore, these biomarkers were expressed in respectively 88 %, 71 %, 69 %, and 67 % of the pancreatic adenocarcinoma patients. The results of this study show that integrin α v β 6 , CEA, EGFR, and uPAR are suitable targets for tumor-specific imaging of pancreatic adenocarcinoma.

  7. Optimizing target selection and development strategy in cancer treatment: the next wave.

    Science.gov (United States)

    Sausville, Edward A

    2004-09-01

    Successful cancer treatments of the future are being developed with a focus on the molecular targets underlying the pathophysiology of neoplasia. Prominent targets which have emerged are those which are mutated in the course of a cancer's development, and mediate activation or release from suppression of pathways mediating proliferation or apoptosis. These arguably are "pathogenic" targets. However, equally important are targets which can be defined on the basis of "large scale" analysis techniques of gene or protein expression in tumors which define targets expressed as a result of a tumor's differentiation state or tissue of origin ("ontogenic" targets); targets mediating drug uptake or metabolism ("pharmacologic" targets), and "microenvironmental" targets mediating the alteration of tumor stromal elements. Irrespective of the nature of the molecular target which is the focus of new therapeutic efforts, target definition in susceptible tumors or patients ideally would be part of the development plan. In addition, an understanding of the therapeutic index which might be achieved in host vs tumor tissues using a surrogate or actual marker of drug effect ideally would be available from animal models and inform the development strategy in humans.

  8. Effectiveness of a selective alcohol prevention program targeting personality risk factors: Results of interaction analyses.

    Science.gov (United States)

    Lammers, Jeroen; Goossens, Ferry; Conrod, Patricia; Engels, Rutger; Wiers, Reinout W; Kleinjan, Marloes

    2017-08-01

    To explore whether specific groups of adolescents (i.e., scoring high on personality risk traits, having a lower education level, or being male) benefit more from the Preventure intervention with regard to curbing their drinking behaviour. A clustered randomized controlled trial, with participants randomly assigned to a 2-session coping skills intervention or a control no-intervention condition. Fifteen secondary schools throughout The Netherlands; 7 schools in the intervention and 8 schools in the control condition. 699 adolescents aged 13-15; 343 allocated to the intervention and 356 to the control condition; with drinking experience and elevated scores in either negative thinking, anxiety sensitivity, impulsivity or sensation seeking. Differential effectiveness of the Preventure program was examined for the personality traits group, education level and gender on past-month binge drinking (main outcome), binge frequency, alcohol use, alcohol frequency and problem drinking, at 12months post-intervention. Preventure is a selective school-based alcohol prevention programme targeting personality risk factors. The comparator was a no-intervention control. Intervention effects were moderated by the personality traits group and by education level. More specifically, significant intervention effects were found on reducing alcohol use within the anxiety sensitivity group (OR=2.14, CI=1.40, 3.29) and reducing binge drinking (OR=1.76, CI=1.38, 2.24) and binge drinking frequency (β=0.24, p=0.04) within the sensation seeking group at 12months post-intervention. Also, lower educated young adolescents reduced binge drinking (OR=1.47, CI=1.14, 1.88), binge drinking frequency (β=0.25, p=0.04), alcohol use (OR=1.32, CI=1.06, 1.65) and alcohol use frequency (β=0.47, p=0.01), but not those in the higher education group. Post hoc latent-growth analyses revealed significant effects on the development of binge drinking (β=-0.19, p=0.02) and binge drinking frequency (β=-0.10, p=0

  9. 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

  10. Nicotine facilitates nicotinic acetylcholine receptor targeting to mitochondria but makes them less susceptible to selective ligands.

    Science.gov (United States)

    Uspenska, Kateryna; Lykhmus, Olena; Gergalova, Galyna; Chernyshov, Volodymyr; Arias, Hugo R; Komisarenko, Sergiy; Skok, Maryna

    2017-08-24

    Several nicotinic acetylcholine receptor (nAChR) subtypes are expressed in mitochondria to regulate the internal pathway of apoptosis in ion channel-independent manner. However, the mechanisms of nAChR activation in mitochondria and targeting to mitochondria are still unknown. Nicotine has been shown to favor nAChR pentamer assembly, folding, and maturation on the way of biosynthesis. The idea of the present work was to determine whether nicotine affects the content, glycosylation, and function of mitochondrial nAChRs. Experiments were performed in isolated liver mitochondria from mice, that either consumed or not nicotine with the drinking water (200μL/L) for 7days. Mitochondria detergent lysates were studied by sandwich or lectin ELISA for the presence and carbohydrate composition of different nAChR subunits. Intact mitochondria were examined by flow cytometry for the binding of fluorescently labeled α-cobratoxin and were tested in functional assay of cytochrome c release under the effect of either Ca 2+ or wortmannin in the presence or absence of nAChR-selective ligands, including PNU-282987 (1nM), dihydro-β-erythroidine (DhβE, 1μM), PNU-120596 (0.3, 3, or 10μM) and desformylflustrabromine hydrochloride (dFBr, 0.001, 0.3, or 1μM). It was found that nicotine consumption increased the ratio of mitochondrial vs non-mitochondrial nAChRs in the liver, enhanced fucosylation of mitochondrial nAChRs, but prevented the binding of α-cobratoxin and the cytochrome c release-attenuating effects of nAChR-specific agonists, antagonists, or positive allosteric modulators. It is concluded that nicotine consumption in vivo favors nAChR glycosylation and trafficking to mitochondria but makes them less susceptible to the effects of specific ligands. Copyright © 2017 Elsevier B.V. All rights reserved.

  11. Development of novel agents for idiopathic pulmonary fibrosis: progress in target selection and clinical trial design.

    Science.gov (United States)

    O'Riordan, Thomas G; Smith, Victoria; Raghu, Ganesh

    2015-10-01

    Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal disease. Until recently, the standard therapy for this disease has been essentially supportive, with the exception of a minority of patients who were eligible for lung transplantation. The development pathway for novel medications for IPF has been complicated. There have been several challenges, including an incomplete understanding of the pathogenesis, unpredictable clinical course, lack of validated biomarkers, the low clinical predictive value of animal models of lung injury, and the need to commit to large clinical trials of long duration to obtain initial evidence of clinical efficacy. Despite these challenges, the combination of recent advances in translational medicine and the unprecedented increase in clinical data accumulated from recent large clinical trials has stimulated an increase in the number of clinical development programs for IPF. Clinical programs are increasingly characterized by rational target selection, preclinical optimization of therapeutic molecules, and an emphasis on efficient clinical trial design. A lower rate of functional decline in patients treated with pirfenidone and nintedanib was demonstrated in large clinical trials. In October 2014, these two drugs became the first agents to be approved by the US Food and Drug Administration for the treatment of IPF. (Pirfenidone had already been approved in several countries outside the United States.) In November 2014, the European Medicines Agency approved the use of nintedanib for IPF. The landscape for management of IPF has markedly changed with the advent of approved therapeutic options for IPF. In this article, we review the strategies that are being used to increase the likelihood of success in clinical development programs of novel disease-modifying agents in IPF.

  12. 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.

  13. Target-triggered transcription machinery for ultra-selective and sensitive fluorescence detection of nucleoside triphosphates in one minute.

    Science.gov (United States)

    Dong, Jiantong; Wu, Tongbo; Xiao, Yu; Chen, Lu; Xu, Lei; Li, Mengyuan; Zhao, Meiping

    2018-02-15

    Nucleoside triphosphates (NTPs) play important roles in living organisms. However, no fluorescent assays are currently available to simply and rapidly detect multiple NTPs with satisfactory selectivity, sensitivity and low cost. Here we demonstrate for the first time a target-triggered in-vitro transcription machinery for ultra-selective, sensitive and instant fluorescence detection of multiple NTPs. The machinery assembles RNA polymerase, DNA template and non-target NTPs to convert the target NTP into equivalent RNA signal sequences which are monitored by the fluorescence enhancement of molecular beacon. The machinery offers excellent selectivity for the target NTP against NDP, NMP and dNTP. Notably, to accelerate the kinetics of the machinery while maintain its high specificity, we investigated the sequence of DNA templates systematically and established a set of guidelines for the design of the optimum DNA templates, which allowed for instant detection of the target NTP at fmol level in less than 1min. Furthermore, the machinery could be transformed into logic gates to study the coeffects of two NTPs in biosynthesis and real-time monitoring systems to reflect the distribution of NTP in nucleotide pools. These results provide very useful and low-cost tools for both biochemical tests and point-of-care analysis. Copyright © 2017 Elsevier B.V. All rights reserved.

  14. 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,…

  15. 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. Copyright © 2014. Published by Elsevier Inc.

  16. 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.

  17. 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

  18. Restoration for the future: Setting endpoints and targets and selecting indicators of progress and success

    Science.gov (United States)

    Daniel C. Dey; Callie Jo Schweitzer; John M. Kabrick

    2014-01-01

    Setting endpoints and targets in forest restoration is a complicated task that is best accomplished in cooperative partnerships that account for the ecology of the system, production of desired ecosystem goods and services, economics and well-being of society, and future environments. Clearly written and quantitative endpoints and intermediary targets need to be...

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

    NARCIS (Netherlands)

    Schneider, C.A.R.; 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

  20. Target-specific NMR detection of protein-ligand interactions with antibody-relayed 15N-group selective STD.

    Science.gov (United States)

    Hetényi, Anasztázia; Hegedűs, Zsófia; Fajka-Boja, Roberta; Monostori, Éva; Kövér, Katalin E; Martinek, Tamás A

    2016-12-01

    Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein-ligand interactions is a key element. 1 H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed 15 N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A 15 N-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system.

  1. Comparing the selection and placement of best management practices in improving water quality using a multiobjective optimization and targeting method.

    Science.gov (United States)

    Chiang, Li-Chi; Chaubey, Indrajeet; Maringanti, Chetan; Huang, Tao

    2014-03-11

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

  2. 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. Iterative optimization yields Mcl-1-targeting stapled peptides with selective cytotoxicity to Mcl-1-dependent cancer cells.

    Science.gov (United States)

    Rezaei Araghi, Raheleh; Bird, Gregory H; Ryan, Jeremy A; Jenson, Justin M; Godes, Marina; Pritz, Jonathan R; Grant, Robert A; Letai, Anthony; Walensky, Loren D; Keating, Amy E

    2018-01-30

    Bcl-2 family proteins regulate apoptosis, and aberrant interactions of overexpressed antiapoptotic family members such as Mcl-1 promote cell transformation, cancer survival, and resistance to chemotherapy. Discovering potent and selective Mcl-1 inhibitors that can relieve apoptotic blockades is thus a high priority for cancer research. An attractive strategy for disabling Mcl-1 involves using designer peptides to competitively engage its binding groove, mimicking the structural mechanism of action of native sensitizer BH3-only proteins. We transformed Mcl-1-binding peptides into α-helical, cell-penetrating constructs that are selectively cytotoxic to Mcl-1-dependent cancer cells. Critical to the design of effective inhibitors was our introduction of an all-hydrocarbon cross-link or "staple" that stabilizes α-helical structure, increases target binding affinity, and independently confers binding specificity for Mcl-1 over related Bcl-2 family paralogs. Two crystal structures of complexes at 1.4 Å and 1.9 Å resolution demonstrate how the hydrophobic staple induces an unanticipated structural rearrangement in Mcl-1 upon binding. Systematic sampling of staple location and iterative optimization of peptide sequence in accordance with established design principles provided peptides that target intracellular Mcl-1. This work provides proof of concept for the development of potent, selective, and cell-permeable stapled peptides for therapeutic targeting of Mcl-1 in cancer, applying a design and validation workflow applicable to a host of challenging biomedical targets.

  4. In vitro HIV-1 selective integration into the target sequence and decoy-effect of the modified sequence.

    Directory of Open Access Journals (Sweden)

    Tatsuaki Tsuruyama

    Full Text Available Although there have been a few reports that the HIV-1 genome can be selectively integrated into the genomic DNA of cultured host cell, the biochemistry of integration selectivity has not been fully understood. We modified the in vitro integration reaction protocol and developed a reaction system with higher efficiency. We used a substrate repeat, 5'-(GTCCCTTCCCAGT(n(ACTGGGAAGGGAC(n-3', and a modified sequence DNA ligated into a circular plasmid. CAGT and ACTG (shown in italics in the above sequence in the repeat units originated from the HIV-1 proviral genome ends. Following the incubation of the HIV-1 genome end cDNA and recombinant integrase for the formation of the pre-integration (PI complex, substrate DNA was reacted with this complex. It was confirmed that the integration selectively occurred in the middle segment of the repeat sequence. In addition, integration frequency and selectivity were positively correlated with repeat number n. On the other hand, both frequency and selectivity decreased markedly when using sequences with deletion of CAGT in the middle position of the original target sequence. Moreover, on incubation with the deleted DNAs and original sequence, the integration efficiency and selectivity for the original target sequence were significantly reduced, which indicated interference effects by the deleted sequence DNAs. Efficiency and selectivity were also found to vary discontinuously with changes in manganese dichloride concentration in the reaction buffer, probably due to its influence on the secondary structure of substrate DNA. Finally, integrase was found to form oligomers on the binding site and substrate DNA formed a loop-like structure. In conclusion, there is a considerable selectivity in HIV-integration into the specified sequence; however, similar DNA sequences can interfere with the integration process, and it is therefore difficult for in vivo integration to occur selectively in the actual host genome DNA.

  5. 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

    2015-01-01

    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. PMID:26183780

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

    Science.gov (United States)

    Accardo, Antonella; Aloj, Luigi; Aurilio, Michela; Morelli, Giancarlo; Tesauro, Diego

    2014-01-01

    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.

  7. 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.

  8. 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.

    1994-03-01

    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.

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

    Directory of Open Access Journals (Sweden)

    Martin C. Boonstra

    2016-01-01

    Full Text Available 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.

  10. 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

    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......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...

  11. Automatic parameter adjustment of difference of Gaussian (DoG) filter to improve OT-MACH filter performance for target recognition applications

    Science.gov (United States)

    Alkandri, Ahmad; Gardezi, Akber; Bangalore, Nagachetan; Birch, Philip; Young, Rupert; Chatwin, Chris

    2011-11-01

    A wavelet-modified frequency domain Optimal Trade-off Maximum Average Correlation Height (OT-MACH) filter has been trained using 3D CAD models and tested on real target images acquired from a Forward Looking Infra Red (FLIR) sensor. The OT-MACH filter can be used to detect and discriminate predefined targets from a cluttered background. The FLIR sensor extends the filter's ability by increasing the range of detection by exploiting the heat signature differences between the target and the background. A Difference of Gaussians (DoG) based wavelet filter has been use to improve the OT-MACH filter discrimination ability and distortion tolerance. Choosing the right standard deviation values of the two Gaussians comprising the filter is critical. In this paper we present a new technique for auto adjustment of the DoG filter parameters driven by the expected target size. Tests were carried on images acquired by the Apache AH-64 helicopter mounted FLIR sensor, results showing an overall improvement in the recognition of target objects present within the IR images.

  12. SPIDERS: selection of spectroscopic targets using AGN candidates detected in all-sky X-ray surveys

    Science.gov (United States)

    Dwelly, T.; Salvato, M.; Merloni, A.; Brusa, M.; Buchner, J.; Anderson, S. F.; Boller, Th.; Brandt, W. N.; Budavári, T.; Clerc, N.; Coffey, D.; Del Moro, A.; Georgakakis, A.; Green, P. J.; Jin, C.; Menzel, M.-L.; Myers, A. D.; Nandra, K.; Nichol, R. C.; Ridl, J.; Schwope, A. D.; Simm, T.

    2017-07-01

    SPIDERS (SPectroscopic IDentification of eROSITA Sources) is a Sloan Digital Sky Survey IV (SDSS-IV) survey running in parallel to the Extended Baryon Oscillation Spectroscopic Survey (eBOSS) cosmology project. SPIDERS will obtain optical spectroscopy for large numbers of X-ray-selected active galactic nuclei (AGN) and galaxy cluster members detected in wide-area eROSITA, XMM-Newton and ROSAT surveys. We describe the methods used to choose spectroscopic targets for two sub-programmes of SPIDERS X-ray selected AGN candidates detected in the ROSAT All Sky and the XMM-Newton Slew surveys. We have exploited a Bayesian cross-matching algorithm, guided by priors based on mid-IR colour-magnitude information from the Wide-field Infrared Survey Explorer survey, to select the most probable optical counterpart to each X-ray detection. We empirically demonstrate the high fidelity of our counterpart selection method using a reference sample of bright well-localized X-ray sources collated from XMM-Newton, Chandra and Swift-XRT serendipitous catalogues, and also by examining blank-sky locations. We describe the down-selection steps which resulted in the final set of SPIDERS-AGN targets put forward for spectroscopy within the eBOSS/TDSS/SPIDERS survey, and present catalogues of these targets. We also present catalogues of ˜12 000 ROSAT and ˜1500 XMM-Newton Slew survey sources that have existing optical spectroscopy from SDSS-DR12, including the results of our visual inspections. On completion of the SPIDERS programme, we expect to have collected homogeneous spectroscopic redshift information over a footprint of ˜7500 deg2 for >85 per cent of the ROSAT and XMM-Newton Slew survey sources having optical counterparts in the magnitude range 17 < r < 22.5, producing a large and highly complete sample of bright X-ray-selected AGN suitable for statistical studies of AGN evolution and clustering.

  13. Target-selective phototherapy using a ligand-based photosensitizer for type 2 cannabinoid receptor.

    Science.gov (United States)

    Zhang, Shaojuan; Jia, Ningyang; Shao, Pin; Tong, Qin; Xie, Xiang-Qun; Bai, Mingfeng

    2014-03-20

    Phototherapy is a powerful, noninvasive approach for cancer treatment, with several agents currently in clinical use. Despite the progress and promise, most current phototherapy agents have serious side effects as they can lead to damage to healthy tissue, even when the photosensitizers are fused to targeting molecules due to nonspecific light activation of the unbound photosensitizer. To overcome these limitations, we developed a phototherapy agent that combines a functional ligand and a near infrared phthalocyanine dye. Our target is type 2 cannabinoid receptor (CB2R), considered an attractive therapeutic target for phototherapy given it is overexpressed by many types of cancers that are located at a surface or can be reached by an endoscope. We show that our CB2R-targeted phototherapy agent, IR700DX-mbc94, is specific for CB2R and effective only when bound to the target receptor. Overall, this opens up the opportunity for development of an alternative treatment option for CB2R-positive cancers. Copyright © 2014 Elsevier Ltd. All rights reserved.

  14. Joint Selection of Transmitters and Receivers in Distributed Multi-input Multi-output Radar Network for Multiple Targets Tracking

    Directory of Open Access Journals (Sweden)

    Lu Yanxi

    2017-02-01

    Full Text Available Only a subset of transmitters and receivers in a distributed Multi-Input Multi-Output (MIMO radar network is allowed to actively track a target at a particular instance due to the limited time and energy resource of a MIMO radar network. It is therefore desirable to obtain an efficient method to overcome the resource constraints while optimizing the tracking performance. In this study, posterior Cramer-Rao lower bound is used as the performance metric and the selection problem is formulated as a Boolean programming problem aiming at optimizing the worst tracking performance of multiple targets. It is later relaxed to a semidefinite programming and solved by the block coordinate descend method. Numerical results show that proposed method superior to the fixed selection method. In addition, with less computation complexity, the proposed method obtains nearly equivalent performance compared with exhaustive search method.

  15. 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...

  16. Method for selecting hollow microspheres for use in laser fusion targets

    Science.gov (United States)

    Farnum, Eugene H.; Fries, R. Jay; Havenhill, Jerry W.; Smith, Maurice Lee; Stoltz, Daniel L.

    1976-01-01

    Hollow microspheres having thin and very uniform wall thickness are useful as containers for the deuterium and tritium gas mixture used as a fuel in laser fusion targets. Hollow microspheres are commercially available; however, in commercial lots only a very small number meet the rigid requirements for use in laser fusion targets. Those meeting these requirements may be separated from the unsuitable ones by subjecting the commercial lot to size and density separations and then by subjecting those hollow microspheres thus separated to an external pressurization at which those which are aspherical or which have nonuniform walls are broken and separating the sound hollow microspheres from the broken ones.

  17. Algal Bioremediation of Waste Waters from Land-Based Aquaculture Using Ulva: Selecting Target Species and Strains

    OpenAIRE

    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 wh...

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

    Science.gov (United States)

    Ramos Alvarenga, René F; Friesen, J Brent; Nikolić, Dejan; Simmler, Charlotte; Napolitano, José G; van Breemen, Richard; Lankin, David C; McAlpine, James B; Pauli, Guido F; Chen, Shao-Nong

    2014-12-26

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid-liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGNER extract = total extract ± target compound(s). Expanding the scope of the recently reported depletion of extracts by immunoaffinity or solid phase liquid chromatography, the present approach allows a more flexible, single- or multi-targeted removal of constituents from complex extracts such as botanicals. Chemical subtraction enables both chemical and biological characterization, including detection of synergism/antagonism by both the subtracted targets and the remaining metabolite mixture, as well as definition of the residual complexity of all fractions. The feasibility of the DESIGNER concept is shown by K-targeted subtraction of four bioactive prenylated phenols, isoxanthohumol (1), 8-prenylnaringenin (2), 6-prenylnaringenin (3), and xanthohumol (4), from a standardized hops (Humulus lupulus L.) extract using specific solvent systems. Conversely, adding K-targeted isolates allows enrichment of the original extract and hence provides an augmented DESIGNER material. Multiple countercurrent separation steps were used to purify each of the four compounds, and four DESIGNER extracts with varying depletions were prepared. The DESIGNER approach innovates the characterization of chemically complex extracts through integration of enabling technologies such as countercurrent separation, K-by-bioactivity, the residual complexity concepts, as well as quantitative analysis by (1)H NMR, LC-MS, and HiFSA-based NMR fingerprinting.

  19. Optimisation of high-performance liquid chromatography with diode array detection using an automatic peak tracking procedure based on augmented iterative target transformation factor analysis

    NARCIS (Netherlands)

    van Zomeren, Paul; Hoogvorst, A.; Coenegracht, P.M J; de Jong, G.J.

    2004-01-01

    An automated method for the optimisation of high-performance liquid chromatography is developed. First of all, the sample of interest is analysed with various eluent compositions. All obtained data are combined into one augmented data matrix. Subsequently, augmented iterative target transformation

  20. Genetic Manipulation of Lactococcus lactis by Using Targeted Group II Introns: Generation of Stable Insertions without Selection

    Science.gov (United States)

    Frazier, Courtney L.; San Filippo, Joseph; Lambowitz, Alan M.; Mills, David A.

    2003-01-01

    Despite their commercial importance, there are relatively few facile methods for genomic manipulation of the lactic acid bacteria. Here, the lactococcal group II intron, Ll.ltrB, was targeted to insert efficiently into genes encoding malate decarboxylase (mleS) and tetracycline resistance (tetM) within the Lactococcus lactis genome. Integrants were readily identified and maintained in the absence of a selectable marker. Since splicing of the Ll.ltrB intron depends on the intron-encoded protein, targeted invasion with an intron lacking the intron open reading frame disrupted TetM and MleS function, and MleS activity could be partially restored by expressing the intron-encoded protein in trans. Restoration of splicing from intron variants lacking the intron-encoded protein illustrates how targeted group II introns could be used for conditional expression of any gene. Furthermore, the modified Ll.ltrB intron was used to separately deliver a phage resistance gene (abiD) and a tetracycline resistance marker (tetM) into mleS, without the need for selection to drive the integration or to maintain the integrant. Our findings demonstrate the utility of targeted group II introns as a potential food-grade mechanism for delivery of industrially important traits into the genomes of lactococci. PMID:12571038

  1. Nuclear pore component Nup98 is a potential tumor suppressor and regulates posttranscriptional expression of select p53 target genes.

    Science.gov (United States)

    Singer, Stephan; Zhao, Ruiying; Barsotti, Anthony M; Ouwehand, Anette; Fazollahi, Mina; Coutavas, Elias; Breuhahn, Kai; Neumann, Olaf; Longerich, Thomas; Pusterla, Tobias; Powers, Maureen A; Giles, Keith M; Leedman, Peter J; Hess, Jochen; Grunwald, David; Bussemaker, Harmen J; Singer, Robert H; Schirmacher, Peter; Prives, Carol

    2012-12-14

    The p53 tumor suppressor utilizes multiple mechanisms to selectively regulate its myriad target genes, which in turn mediate diverse cellular processes. Here, using conventional and single-molecule mRNA analyses, we demonstrate that the nucleoporin Nup98 is required for full expression of p21, a key effector of the p53 pathway, but not several other p53 target genes. Nup98 regulates p21 mRNA levels by a posttranscriptional mechanism in which a complex containing Nup98 and the p21 mRNA 3'UTR protects p21 mRNA from degradation by the exosome. An in silico approach revealed another p53 target (14-3-3σ) to be similarly regulated by Nup98. The expression of Nup98 is reduced in murine and human hepatocellular carcinomas (HCCs) and correlates with p21 expression in HCC patients. Our study elucidates a previously unrecognized function of wild-type Nup98 in regulating select p53 target genes that is distinct from the well-characterized oncogenic properties of Nup98 fusion proteins. Copyright © 2012 Elsevier Inc. All rights reserved.

  2. Highly stable aptamers selected from a 2'-fully modified fGmH RNA library for targeting biomaterials.

    Science.gov (United States)

    Friedman, Adam D; Kim, Dongwook; Liu, Rihe

    2015-01-01

    When developed as targeting ligands for the in vivo delivery of biomaterials to biological systems, RNA aptamers immediately face numerous obstacles, in particular nuclease degradation and post-selection 2' modification. This study aims to develop a novel class of highly stable, 2'-fully modified RNA aptamers that are ideal for the targeted delivery of biomaterials. We demonstrated the facile transcription of a fGmH (2'-F-dG, 2'-OMe-dA/dC/dU) RNA library with unexpected hydrophobicity, the direct selection of aptamers from a fGmH RNA library that bind Staphylococcus aureus Protein A (SpA) as a model target, and the superior nuclease and serum stability of these aptamers compared to 2'-partially modified RNA variants. Characterizations of fGmH RNA aptamers binding to purified SpA and to endogenous SpA present on the surface of S. aureus cells demonstrate fGmH RNA aptamer selectivity and stability. Significantly, fGmH RNA aptamers were able to functionalize, stabilize, and specifically deliver aggregation-prone silver nanoparticles (AgNPs) to S. aureus with SpA-dependent antimicrobial effects. This study describes a novel aptamer class with considerable potential to improve the in vivo applicability of nucleic acid-based affinity molecules to biomaterials.

  3. Automatic face morphing for transferring facial animation

    NARCIS (Netherlands)

    Bui Huu Trung, B.H.T.; Bui, T.D.; Poel, Mannes; Heylen, Dirk K.J.; Nijholt, Antinus; Hamza, H.M.

    2003-01-01

    In this paper, we introduce a novel method of automatically finding the training set of RBF networks for morphing a prototype face to represent a new face. This is done by automatically specifying and adjusting corresponding feature points on a target face. The RBF networks are then used to transfer

  4. Selection and Characterization of Single Chain Antibody Fragments Specific for Hsp90 as a Potential Cancer Targeting Molecule

    Directory of Open Access Journals (Sweden)

    Edyta Petters

    2015-08-01

    Full Text Available Heat shock proteins play an essential role in facilitating malignant transformation and they have been recognized as important factors in human cancers. One of the key elements of the molecular chaperones machinery is Hsp90 and it has recently become a target for anticancer therapeutic approaches. The potential and importance of Hsp90-directed agents becomes apparent when one realizes that disruption of Hsp90 function may influence over 200 oncogenic client proteins. Here, we described the selection and characterization of Hsp90-specific antibody fragments from commercially available Tomlinson I and J phage display libraries. The affinities of Hsp90-binding scFv variants were measured using SPR method. Then, based on the best clone selected, we performed the affinity maturation procedure and obtained valuable Hsp90-specific clones. The selected binders were expressed and applied for immunostaining, ELISA and SPR analysis using model cancer cell lines. All performed experiments confirmed the ability of selected antibodies to interact with the Hsp90. Therefore, the presented Hsp90-specific scFv, might be a starting point for the development of a novel antibody-based strategy targeting cancer.

  5. Target guided synthesis using DNA nano-templates for selectively assembling a G-quadruplex binding c-MYC inhibitor

    Science.gov (United States)

    Panda, Deepanjan; Saha, Puja; Das, Tania; Dash, Jyotirmayee

    2017-07-01

    The development of small molecules is essential to modulate the cellular functions of biological targets in living system. Target Guided Synthesis (TGS) approaches have been used for the identification of potent small molecules for biological targets. We herein demonstrate an innovative example of TGS using DNA nano-templates that promote Huisgen cycloaddition from an array of azide and alkyne fragments. A G-quadruplex and a control duplex DNA nano-template have been prepared by assembling the DNA structures on gold-coated magnetic nanoparticles. The DNA nano-templates facilitate the regioselective formation of 1,4-substituted triazole products, which are easily isolated by magnetic decantation. The G-quadruplex nano-template can be easily recovered and reused for five reaction cycles. The major triazole product, generated by the G-quadruplex inhibits c-MYC expression by directly targeting the c-MYC promoter G-quadruplex. This work highlights that the nano-TGS approach may serve as a valuable strategy to generate target-selective ligands for drug discovery.

  6. 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.

  7. Many gases and many measures. Choice of targets and selection of measures in climate policy

    Energy Technology Data Exchange (ETDEWEB)

    Aaheim, H. Asbjoern

    1997-12-31

    This report studies a mix of measures to reduce emissions of CO{sub 2}, CH{sub 4} and N{sub 2}O. It starts with a discussion of so-called direct measures and relates them to charges on emissions of fossil fuels in order to assess conditions for an optimal combination of the two. It then establishes cost functions for direct measures based on Norwegian data and discusses the calculation model. It further describes the atemporal conditions, which are relevant for a policy with emission targets and studies the implications for the choice of direct and indirect measures as well as the emphasis on different gases. In the final section, the intertemporal approach is taken, where the targets are related to concentrations of greenhouse gases by their radiative forcing. 15 refs., 19 figs., 1 table

  8. Evaluation of Alternative Splicing Regulators as Targets for Selective Therapy of Triple Negative (Basal) Breast Carcinoma

    Science.gov (United States)

    2017-10-01

    are generating the experimental animals that combine the transgene with the knockout alleles. Under Task 4, we analyzed the expression of KHDRBS3 in...tumorigenesis process and identify potential therapeutic targets. This will be accomplished through series of experiments in vitro and on animal ...We have already produced KHDRBS3(-/+); C3.1-Tag animals and these are now bred with KHDRBS3(-/-) animals to place the transgene in complete

  9. Hunting Leadership Targets in Counterinsurgency and Counterterrorist Operations: Selected Perspectives and Experience

    Science.gov (United States)

    2007-06-01

    efficacy of leadership targeting spans a broad spec- trum from highly successful in the case of Peru and the Sendero Luminoso in the 1990s to the less...countries from Central America to Argentina. In the Andean Ridge area, Colombia and Peru have been particularly notable. Among the largest and most intense...followers as “ Presidente Gonzalo” and the “Fourth Sword of Marxism” (joining Marx, Lenin and Mao), he had embraced Maoism in his travels to China

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

    Science.gov (United States)

    Ravnskjaer, Kim; Kester, Henri; Liu, Yi; Zhang, Xinmin; Lee, Dong; Yates, John R; Montminy, Marc

    2007-06-20

    A number of hormones and growth factors stimulate gene expression by promoting the phosphorylation of CREB (P-CREB), thereby enhancing its association with the histone acetylase paralogs p300 and CBP (CBP/p300). Relative to cAMP, stress signals trigger comparable amounts of CREB phosphorylation, 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-mediated transcription in cells exposed to stress signals. Taken together, these results indicate that TORC2 is one of the long sought after cofactors that mediates the differential effects of cAMP and stress pathways on CREB target gene expression.

  11. Variable selection for confounder control, flexible modeling and Collaborative Targeted Minimum Loss-based Estimation in causal inference

    Science.gov (United States)

    Schnitzer, Mireille E.; Lok, Judith J.; Gruber, Susan

    2015-01-01

    This paper investigates the appropriateness of the integration of flexible propensity score modeling (nonparametric or machine learning approaches) in semiparametric models for the estimation of a causal quantity, such as the mean outcome under treatment. We begin with an overview of some of the issues involved in knowledge-based and statistical variable selection in causal inference and the potential pitfalls of automated selection based on the fit of the propensity score. Using a simple example, we directly show the consequences of adjusting for pure causes of the exposure when using inverse probability of treatment weighting (IPTW). Such variables are likely to be selected when using a naive approach to model selection for the propensity score. We describe how the method of Collaborative Targeted minimum loss-based estimation (C-TMLE; van der Laan and Gruber, 2010) capitalizes on the collaborative double robustness property of semiparametric efficient estimators to select covariates for the propensity score based on the error in the conditional outcome model. Finally, we compare several approaches to automated variable selection in low-and high-dimensional settings through a simulation study. From this simulation study, we conclude that using IPTW with flexible prediction for the propensity score can result in inferior estimation, while Targeted minimum loss-based estimation and C-TMLE may benefit from flexible prediction and remain robust to the presence of variables that are highly correlated with treatment. However, in our study, standard influence function-based methods for the variance underestimated the standard errors, resulting in poor coverage under certain data-generating scenarios. PMID:26226129

  12. Automatic readout micrometer

    Science.gov (United States)

    Lauritzen, T.

    A measuring system is described for surveying and very accurately positioning objects with respect to a reference line. A principle use of this surveying system is for accurately aligning the electromagnets which direct a particle beam emitted from a particle accelerator. Prior art surveying systems require highly skilled surveyors. Prior art systems include, for example, optical surveying systems which are susceptible to operator reading errors, and celestial navigation-type surveying systems, with their inherent complexities. The present invention provides an automatic readout micrometer which can very accurately measure distances. The invention has a simplicity of operation which practically eliminates the possibilities of operator optical reading error, owning to the elimination of traditional optical alignments for making measurements. The invention has an extendable arm which carries a laser surveying target. The extendable arm can be continuously positioned over its entire length of travel by either a coarse of fine adjustment without having the fine adjustment outrun the coarse adjustment until a reference laser beam is centered on the target as indicated by a digital readout. The length of the micrometer can then be accurately and automatically read by a computer and compared with a standardized set of alignment measurements. Due to its construction, the micrometer eliminates any errors due to temperature changes when the system is operated within a standard operating temperature range.

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

    NARCIS (Netherlands)

    Rawle, C.J.; Miall, R.C.; Praamstra, P.

    2012-01-01

    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

  14. Drugability of extracellular targets: discovery of small molecule drugs targeting allosteric, functional, and subunit-selective sites on GPCRs and ion channels.

    Science.gov (United States)

    Grigoriadis, Dimitri E; Hoare, Samuel R J; Lechner, Sandra M; Slee, Deborah H; Williams, John A

    2009-01-01

    Beginning with the discovery of the structure of deoxyribose nucleic acid in 1953, by James Watson and Francis Crick, the sequencing of the entire human genome some 50 years later, has begun to quantify the classes and types of proteins that may have relevance to human disease with the promise of rapidly identifying compounds that can modulate these proteins so as to have a beneficial and therapeutic outcome. This so called 'drugable space' involves a variety of membrane-bound proteins including the superfamily of G-protein-coupled receptors (GPCRs), ion channels, and transporters among others. The recent number of novel therapeutics targeting membrane-bound extracellular proteins that have reached the market in the past 20 years however pales in magnitude when compared, during the same timeframe, to the advancements made in the technologies available to aid in the discovery of these novel therapeutics. This review will consider select examples of extracellular drugable targets and focus on the GPCRs and ion channels highlighting the corticotropin releasing factor (CRF) type 1 and gamma-aminobutyric acid receptors, and the Ca(V)2.2 voltage-gated ion channel. These examples will elaborate current technological advancements in drug discovery and provide a prospective framework for future drug development.

  15. 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.)

  16. Evolution of NADPH Oxidase Inhibitors: Selectivity and Mechanisms for Target Engagement

    Science.gov (United States)

    Altenhöfer, Sebastian; Radermacher, Kim A.; Kleikers, Pamela W.M.; Wingler, Kirstin

    2015-01-01

    Abstract Significance: Oxidative stress, an excess of reactive oxygen species (ROS) production versus consumption, may be involved in the pathogenesis of different diseases. The only known enzymes solely dedicated to ROS generation are nicotinamide adenine dinucleotide phosphate (NADPH) oxidases with their catalytic subunits (NOX). After the clinical failure of most antioxidant trials, NOX inhibitors are the most promising therapeutic option for diseases associated with oxidative stress. Recent Advances: Historical NADPH oxidase inhibitors, apocynin and diphenylene iodonium, are un-specific and not isoform selective. Novel NOX inhibitors stemming from rational drug discovery approaches, for example, GKT137831, ML171, and VAS2870, show improved specificity for NADPH oxidases and moderate NOX isoform selectivity. Along with NOX2 docking sequence (NOX2ds)-tat, a peptide-based inhibitor, the use of these novel small molecules in animal models has provided preliminary in vivo evidence for a pathophysiological role of specific NOX isoforms. Critical Issues: Here, we discuss whether novel NOX inhibitors enable reliable validation of NOX isoforms' pathological roles and whether this knowledge supports translation into pharmacological applications. Modern NOX inhibitors have increased the evidence for pathophysiological roles of NADPH oxidases. However, in comparison to knockout mouse models, NOX inhibitors have limited isoform selectivity. Thus, their use does not enable clear statements on the involvement of individual NOX isoforms in a given disease. Future Directions: The development of isoform-selective NOX inhibitors and biologicals will enable reliable validation of specific NOX isoforms in disease models other than the mouse. Finally, GKT137831, the first NOX inhibitor in clinical development, is poised to provide proof of principle for the clinical potential of NOX inhibition. Antioxid. Redox Signal. 23, 406–427. PMID:24383718

  17. Virotherapy Targeting Cyclin E Overexpression in Tumors with Adenovirus-enhanced Cancer Selective Promoter

    Science.gov (United States)

    Cheng, Pei-Hsin; Rao, Xiao-Mei; Duan, Xiaoxian; Li, Xiao-Feng; Egger, Michael E.; McMasters, Kelly M.; Zhou, H. Sam

    2014-01-01

    Oncolytic virotherapy can selectively destroy cancer cells and is a potential approach in cancer treatment. A strategy to increase tumor-specific selectivity is to control the expression of a key regulatory viral gene with a tumor-specific promoter. We have previously found that cyclin E expression is augmented in cancer cells after adenovirus (Ad) infection. Thus, the cyclin E promoter that is further activated by Ad in cancer cells may have unique properties for enhancing oncolytic viral replication. We have shown that high levels of viral E1a gene expression are achieved in cancer cells infected with Ad-cycE, in which the endogenous Ad E1a promoter was replaced with the cyclin E promoter. Ad-cycE shows markedly selective oncolytic efficacy in vitro and destroys various types of cancer cells, including those resistant to ONYX-015/dl1520. Furthermore, Ad-cycE shows a strong capacity to repress A549 xenograft tumor growth in nude mice and significantly prolongs survival. This study suggests the potential of Ad-cycE in cancer therapy and indicates the advantages of using promoters that can be upregulated by virus infection in cancer cells in development of oncolytic viruses. PMID:25376708

  18. Differential targeting of brain stress circuits with a selective glucocorticoid receptor modulator

    Science.gov (United States)

    Zalachoras, Ioannis; Houtman, René; Atucha, Erika; Devos, Rene; Tijssen, Ans M. I.; Hu, Pu; Lockey, Peter M.; Datson, Nicole A.; Belanoff, Joseph K.; Lucassen, Paul J.; Joëls, Marian; de Kloet, E. Ronald; Roozendaal, Benno; Hunt, Hazel; Meijer, Onno C.

    2013-01-01

    Glucocorticoid receptor (GR) antagonism may be of considerable therapeutic value in stress-related psychopathology such as depression. However, blockade of all GR-dependent processes in the brain will lead to unnecessary and even counteractive effects, such as elevated endogenous cortisol levels. Selective GR modulators are ligands that can act both as agonist and as antagonist and may be used to separate beneficial from harmful treatment effects. We have discovered that the high-affinity GR ligand C108297 is a selective modulator in the rat brain. We first demonstrate that C108297 induces a unique interaction profile between GR and its downstream effector molecules, the nuclear receptor coregulators, compared with the full agonist dexamethasone and the antagonist RU486 (mifepristone). C108297 displays partial agonistic activity for the suppression of hypothalamic corticotropin-releasing hormone (CRH) gene expression and potently enhances GR-dependent memory consolidation of training on an inhibitory avoidance task. In contrast, it lacks agonistic effects on the expression of CRH in the central amygdala and antagonizes GR-mediated reduction in hippocampal neurogenesis after chronic corticosterone exposure. Importantly, the compound does not lead to disinhibition of the hypothalamus–pituitary–adrenal axis. Thus, C108297 represents a class of ligands that has the potential to more selectively abrogate pathogenic GR-dependent processes in the brain, while retaining beneficial aspects of GR signaling. PMID:23613579

  19. Modelling the consequences of targeted selective treatment strategies on performance and emergence of anthelmintic resistance amongst grazing calves

    Directory of Open Access Journals (Sweden)

    Zoe Berk

    2016-12-01

    Full Text Available The development of anthelmintic resistance by helminths can be slowed by maintaining refugia on pasture or in untreated hosts. Targeted selective treatments (TST may achieve this through the treatment only of individuals that would benefit most from anthelmintic, according to certain criteria. However TST consequences on cattle are uncertain, mainly due to difficulties of comparison between alternative strategies. We developed a mathematical model to compare: 1 the most ‘beneficial’ indicator for treatment selection and 2 the method of selection of calves exposed to Ostertagia ostertagi, i.e. treating a fixed percentage of the population with the lowest (or highest indicator values versus treating individuals who exceed (or are below a given indicator threshold. The indicators evaluated were average daily gain (ADG, faecal egg counts (FEC, plasma pepsinogen, combined FEC and plasma pepsinogen, versus random selection of individuals. Treatment success was assessed in terms of benefit per R (BPR, the ratio of average benefit in weight gain to change in frequency of resistance alleles R (relative to an untreated population. The optimal indicator in terms of BPR for fixed percentages of calves treated was plasma pepsinogen and the worst ADG; in the latter case treatment was applied to some individuals who were not in need of treatment. The reverse was found when calves were treated according to threshold criteria, with ADG being the best target indicator for treatment. This was also the most beneficial strategy overall, with a significantly higher BPR value than any other strategy, but its degree of success depended on the chosen threshold of the indicator. The study shows strong support for TST, with all strategies showing improvements on calves treated selectively, compared with whole-herd treatment at 3, 8, 13 weeks post-turnout. The developed model appeared capable of assessing the consequences of other TST strategies on calf populations.

  20. Clinical Application of Targeted Deep Sequencing in Solid-Cancer Patients and Utility for Biomarker-Selected Clinical Trials.

    Science.gov (United States)

    Kim, Seung Tae; Kim, Kyoung-Mee; Kim, Nayoung K D; Park, Joon Oh; Ahn, Soomin; Yun, Jae-Won; Kim, Kyu-Tae; Park, Se Hoon; Park, Peter J; Kim, Hee Cheol; Sohn, Tae Sung; Choi, Dong Il; Cho, Jong Ho; Heo, Jin Seok; Kwon, Wooil; Lee, Hyuk; Min, Byung-Hoon; Hong, Sung No; Park, Young Suk; Lim, Ho Yeong; Kang, Won Ki; Park, Woong-Yang; Lee, Jeeyun

    2017-10-01

    Molecular profiling of actionable mutations in refractory cancer patients has the potential to enable "precision medicine," wherein individualized therapies are guided based on genomic profiling. The molecular-screening program was intended to route participants to different candidate drugs in trials based on clinical-sequencing reports. In this screening program, we used a custom target-enrichment panel consisting of cancer-related genes to interrogate single-nucleotide variants, insertions and deletions, copy number variants, and a subset of gene fusions. From August 2014 through April 2015, 654 patients consented to participate in the program at Samsung Medical Center. Of these patients, 588 passed the quality control process for the 381-gene cancer-panel test, and 418 patients were included in the final analysis as being eligible for any anticancer treatment (127 gastric cancer, 122 colorectal cancer, 62 pancreatic/biliary tract cancer, 67 sarcoma/other cancer, and 40 genitourinary cancer patients). Of the 418 patients, 55 (12%) harbored a biomarker that guided them to a biomarker-selected clinical trial, and 184 (44%) patients harbored at least one genomic alteration that was potentially targetable. This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase. This study demonstrated that the panel-based sequencing program resulted in an increased rate of trial enrollment of metastatic cancer patients into biomarker-selected clinical trials. Given the expanding list of biomarker-selected trials, the guidance percentage to matched trials is anticipated to increase. © AlphaMed Press 2017.

  1. 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.

  2. Oxamate, but Not Selective Targeting of LDH-A, Inhibits Medulloblastoma Cell Glycolysis, Growth and Motility

    Directory of Open Access Journals (Sweden)

    Cara J. Valvona

    2018-03-01

    Full Text Available Medulloblastoma is the most common malignant paediatric brain tumour and current therapies often leave patients with severe neurological disabilities. Four major molecular groups of medulloblastoma have been identified (Wnt, Shh, Group 3 and Group 4, which include additional, recently defined subgroups with different prognosis and genetic characteristics. Lactate dehydrogenase A (LDHA is a key enzyme in the aerobic glycolysis pathway, an abnormal metabolic pathway commonly observed in cancers, associated with tumour progression and metastasis. Studies indicate MBs have a glycolytic phenotype; however, LDHA has not yet been explored as a therapeutic target for medulloblastoma. LDHA expression was examined in medulloblastoma subgroups and cell lines. The effects of LDHA inhibition by oxamate or LDHA siRNA on medulloblastoma cell line metabolism, migration and proliferation were examined. LDHA was significantly overexpressed in Group 3 and Wnt MBs compared to non-neoplastic cerebellum. Furthermore, we found that oxamate significantly attenuated glycolysis, proliferation and motility in medulloblastoma cell lines, but LDHA siRNA did not. We established that aerobic glycolysis is a potential therapeutic target for medulloblastoma, but broader LDH inhibition (LDHA, B, and C may be more appropriate than LDHA inhibition alone.

  3. A targeted ferritin-microplasmin based thrombolytic nanocage selectively dissolves blood clots.

    Science.gov (United States)

    Seo, Junyoung; Al-Hilal, Taslim A; Jee, Jun-Goo; Kim, Yong-Lim; Kim, Ha-Jeong; Lee, Byung-Heon; Kim, Soyoun; Kim, In-San

    2018-04-01

    The use of thrombolytic therapies is limited by an increased risk of systemic hemorrhage due to lysis of hemostatic clots. We sought to develop a plasmin-based thrombolytic nanocage that efficiently dissolves the clot without causing systemic fibrinolysis or disrupting hemostatic clots. Here, we generated a double chambered short-length ferritin (sFt) construct that has an N-terminal region fused to multivalent clot targeting peptides (CLT: CNAGESSKNC) and a C-terminal end fused to a microplasmin (μPn); CLT recognizes fibrin-fibronectin complexes in clots, μPn efficiently dissolves clots, and the assembly of double chambered sFt (CLT-sFt-μPn) into nanocage structure protects the activated-μPn from its circulating inhibitors. Importantly, activated CLT-sFt-μPn thrombolytic nanocage showed a prolonged circulatory life over activated-μPn and efficiently lysed the preexisting clots in both arterial and venous thromboses models. Thus, CLT-sFt-μPn thrombolytic nanocage platform represents the prototype of a targeted clot-busting agent with high efficacy and safety over existing thrombolytic therapies. Copyright © 2018 Elsevier Inc. All rights reserved.

  4. Selective targeting of brain tumors with gold nanoparticle-induced radiosensitization.

    Directory of Open Access Journals (Sweden)

    Daniel Y Joh

    Full Text Available Successful treatment of brain tumors such as glioblastoma multiforme (GBM is limited in large part by the cumulative dose of Radiation Therapy (RT that can be safely given and the blood-brain barrier (BBB, which limits the delivery of systemic anticancer agents into tumor tissue. Consequently, the overall prognosis remains grim. Herein, we report our pilot studies in cell culture experiments and in an animal model of GBM in which RT is complemented by PEGylated-gold nanoparticles (GNPs. GNPs significantly increased cellular DNA damage inflicted by ionizing radiation in human GBM-derived cell lines and resulted in reduced clonogenic survival (with dose-enhancement ratio of ~1.3. Intriguingly, combined GNP and RT also resulted in markedly increased DNA damage to brain blood vessels. Follow-up in vitro experiments confirmed that the combination of GNP and RT resulted in considerably increased DNA damage in brain-derived endothelial cells. Finally, the combination of GNP and RT increased survival of mice with orthotopic GBM tumors. Prior treatment of mice with brain tumors resulted in increased extravasation and in-tumor deposition of GNP, suggesting that RT-induced BBB disruption can be leveraged to improve the tumor-tissue targeting of GNP and thus further optimize the radiosensitization of brain tumors by GNP. These exciting results together suggest that GNP may be usefully integrated into the RT treatment of brain tumors, with potential benefits resulting from increased tumor cell radiosensitization to preferential targeting of tumor-associated vasculature.

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

    Science.gov (United States)

    Kurosawa, Nobuyuki; Yoshioka, Megumi; Isobe, Masaharu

    2011-04-13

    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. 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. 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. © 2011 Kurosawa et al; licensee BioMed Central Ltd.

  6. 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.

  7. 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

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

    Science.gov (United States)

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

    2012-01-01

    The purpose of this review paper is to present evidence that rat animal models of alcoholism provide an ideal platform for developing and screening medications that target alcohol abuse and dependence. The focus is on the 5 oldest international rat lines that have been selectively bred for a high alcohol-consumption phenotype. The behavioral and neurochemical phenotypes of these rat lines are reviewed and placed in the context of the clinical literature. The paper presents behavioral models for assessing the efficacy of pharmaceuticals for the treatment of alcohol abuse and dependence in rodents, with particular emphasis on rats. Drugs that have been tested for their effectiveness in reducing alcohol/ethanol consumption and/or self-administration by these rat lines and their putative site of action are summarized. The paper also presents some current and future directions for developing pharmacological treatments targeting alcohol abuse and dependence. PMID:22841890

  9. 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.

  10. Increasing selective exposure to health messages by targeting person versus behavior schemas.

    Science.gov (United States)

    Pease, Meridith E; Brannon, Laura A; Pilling, Valerie K

    2006-01-01

    Schema correspondence theory (Brannon and Brock, 1994) was applied to the topic of selective exposure to health information. The following question was asked: When do people prefer to expose themselves to health-relevant information tailored to match their own needs and values (i.e., recipient self-schema matching) versus the values and goals that the healthy behavior brings to mind (i.e., behavior schema matching)? In general, recipient self-schema matched messages tended to be preferred over behavior schema matched messages. However, this tendency was attenuated to the extent that the behavior had a very well defined (prototypical) schema.

  11. 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.

  12. Selectivity and Efficiency of Late Transgene Expression by Transcriptionally Targeted Oncolytic Adenoviruses Are Dependent on the Transgene Insertion Strategy

    Science.gov (United States)

    Quirin, Christina; Rohmer, Stanimira; Fernández-Ulibarri, Inés; Behr, Michael; Hesse, Andrea; Engelhardt, Sarah; Erbs, Philippe; Enk, Alexander H.

    2011-01-01

    Abstract Key challenges facing cancer therapy are the development of tumor-specific drugs and potent multimodal regimens. Oncolytic adenoviruses possess the potential to realize both aims by restricting virus replication to tumors and inserting therapeutic genes into the virus genome, respectively. A major effort in this regard is to express transgenes in a tumor-specific manner without affecting virus replication. Using both luciferase as a sensitive reporter and genetic prodrug activation, we show that promoter control of E1A facilitates highly selective expression of transgenes inserted into the late transcription unit. This, however, required multistep optimization of late transgene expression. Transgene insertion via internal ribosome entry site (IRES), splice acceptor (SA), or viral 2A sequences resulted in replication-dependent expression. Unexpectedly, analyses in appropriate substrates and with matching control viruses revealed that IRES and SA, but not 2A, facilitated indirect transgene targeting via tyrosinase promoter control of E1A. Transgene expression via SA was more selective (up to 1,500-fold) but less effective than via IRES. Notably, we also revealed transgene-dependent interference with splicing. Hence, the prodrug convertase FCU1 (a cytosine deaminase–uracil phosphoribosyltransferase fusion protein) was expressed only after optimizing the sequence surrounding the SA site and mutating a cryptic splice site within the transgene. The resulting tyrosinase promoter-regulated and FCU1-encoding adenovirus combined effective oncolysis with targeted prodrug activation therapy of melanoma. Thus, prodrug activation showed potent bystander killing and increased cytotoxicity of the virus up to 10-fold. We conclude that armed oncolytic viruses can be improved substantially by comparing and optimizing strategies for targeted transgene expression, thereby implementing selective and multimodal cancer therapies. PMID:20939692

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

    Science.gov (United States)

    Vilhelmsen, Troels N; Ferré, Ty P A

    2017-09-15

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

  14. Targeting ferritin receptors for the selective delivery of imaging and therapeutic agents to breast cancer cells.

    Science.gov (United States)

    Geninatti Crich, S; Cadenazzi, M; Lanzardo, S; Conti, L; Ruiu, R; Alberti, D; Cavallo, F; Cutrin, J C; Aime, S

    2015-04-21

    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.

  15. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation.

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam; Ardell, Jeffrey L

    2016-11-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. Copyright © 2016 the American Physiological Society.

  16. FOXO3 Selectively Amplifies Enhancer Activity to Establish Target Gene Regulation

    Directory of Open Access Journals (Sweden)

    Astrid Eijkelenboom

    2013-12-01

    Full Text Available Forkhead box O (FOXO transcription factors regulate diverse cellular processes, affecting tumorigenesis, metabolism, stem cell maintenance, and lifespan. We show that FOXO3 transcription regulation mainly proceeds through the most active subset of enhancers. In addition to the general distinction between “open” and “closed” chromatin, we show that the level of activity marks (H3K27ac, RNAPII, enhancer RNAs of these open chromatin regions prior to FOXO3 activation largely determines FOXO3 DNA binding. Consequently, FOXO3 amplifies the levels of these activity marks and their absolute rather than relative changes associate best with FOXO3 target gene regulation. The importance of preexisting chromatin state in directing FOXO3 gene regulation, as shown here, provides a mechanism whereby FOXO3 can regulate cell-specific homeostasis. Genetic variation is reported to affect these chromatin signatures in a quantitative manner, and, in agreement, we observe a correlation between cancer-associated genetic variations and the amplitude of FOXO3 enhancer binding.

  17. 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.

  18. Identification of compounds that selectively target highly chemotherapy refractory neuroblastoma cancer stem cells.

    Science.gov (United States)

    Díaz-Carballo, David; Acikelli, Ali Haydar; Bardenheuer, Walter; Gustmann, Sebastian; Malak, Sascha; Stoll, Raphael; Kedziorski, Thorsten; Nazif, Mhd Ali; Jastrow, Holger; Wennemuth, Gunter; Dammann, Philip; Feigel, Martin; Strumberg, Dirk

    2014-09-01

    Relapse of cancer months or years after an apparently successful therapy is probably caused by cancer stem cells (CSCs) due to their intrinsic features like dormant periods, radiorefraction, and acquired multidrug resistance (MDR) phenotypes, among other mechanisms of cellular drug evasiveness. Thus, the lack of currently efficacious interventions remains a major problem in the treatment of malignancies, together with the inability of existing drugs to destroy specifically CSCs. Neuroblastomas per se are highly chemotherapy-refractory extracranial tumors in infants with very low survival rates. So far, no effective cytostatics against this kind of tumors are clinically available. Therefore, we have put much effort into the development of agents to efficiently combat this malignancy. For this purpose, we tested several compounds isolated from Cuban propolis on induced CSCs (iCSC) derived from LAN-1 neuroblastoma cells which expressed several characteristics of tumor-initiating cells both in in-vitro and in-vivo models. Some small molecules such as flavonoids and polycyclic polyprenylated acylphloroglucinols (PPAP) were isolated using successive RT-HPLC cycles and identified employing mass spectrometry and NMR spectroscopic techniques. Their cytotoxicity was first screened in sensitive cell systems by MTT proliferation assays and afterwards studied in less sensitive neuroblastoma iCSC models. We found several compounds with considerable anti-iCSC activity, most of them belonging to the PPAP class. The majority of the compounds act in a pleiotropic manner on the molecular biology of tumors although their specific targets remain unclear. Nevertheless, two substances, one of them a flavonoid, induced a strong disruption of tubulin polymerization. In addition, an unknown compound strongly inhibited replicative enzymes like toposimerases I/II and DNA polymerase. Here, we report for the first time cytotoxic activities of small molecules isolated from Caribbean propolis

  19. Vagal stimulation targets select populations of intrinsic cardiac neurons to control neurally induced atrial fibrillation

    Science.gov (United States)

    Salavatian, Siamak; Beaumont, Eric; Longpré, Jean-Philippe; Armour, J. Andrew; Vinet, Alain; Jacquemet, Vincent; Shivkumar, Kalyanam

    2016-01-01

    Mediastinal nerve stimulation (MNS) reproducibly evokes atrial fibrillation (AF) by excessive and heterogeneous activation of intrinsic cardiac (IC) neurons. This study evaluated whether preemptive vagus nerve stimulation (VNS) impacts MNS-induced evoked changes in IC neural network activity to thereby alter susceptibility to AF. IC neuronal activity in the right atrial ganglionated plexus was directly recorded in anesthetized canines (n = 8) using a linear microelectrode array concomitant with right atrial electrical activity in response to: 1) epicardial touch or great vessel occlusion vs. 2) stellate or vagal stimulation. From these stressors, post hoc analysis (based on the Skellam distribution) defined IC neurons so recorded as afferent, efferent, or convergent (afferent and efferent inputs) local circuit neurons (LCN). The capacity of right-sided MNS to modify IC activity in the induction of AF was determined before and after preemptive right (RCV)- vs. left (LCV)-sided VNS (15 Hz, 500 μs; 1.2× bradycardia threshold). Neuronal (n = 89) activity at baseline (0.11 ± 0.29 Hz) increased during MNS-induced AF (0.51 ± 1.30 Hz; P < 0.001). Convergent LCNs were preferentially activated by MNS. Preemptive RCV reduced MNS-induced changes in LCN activity (by 70%) while mitigating MNS-induced AF (by 75%). Preemptive LCV reduced LCN activity by 60% while mitigating AF potential by 40%. IC neuronal synchrony increased during neurally induced AF, a local neural network response mitigated by preemptive VNS. These antiarrhythmic effects persisted post-VNS for, on average, 26 min. In conclusion, VNS preferentially targets convergent LCNs and their interactive coherence to mitigate the potential for neurally induced AF. The antiarrhythmic properties imposed by VNS exhibit memory. PMID:27591222

  20. Olesoxime prevents microtubule-targeting drug neurotoxicity: selective preservation of EB comets in differentiated neuronal cells.

    Science.gov (United States)

    Rovini, Amandine; Carré, Manon; Bordet, Thierry; Pruss, Rebecca M; Braguer, Diane

    2010-09-15

    Microtubule-targeting agents (MTAs), anticancer drugs widely used in the clinic, often induce peripheral neuropathy, a main dose-limiting side effect. The mechanism for this neurotoxicity remains poorly understood and there are still no approved therapies for neuropathies triggered by MTAs. Olesoxime (cholest-4-en-3-one, oxime; TRO19622) has shown marked neuroprotective properties in animals treated with paclitaxel and vincristine. The purpose of this study was to investigate its mechanism of neuroprotection against MTA neurotoxicity by using rat and human differentiated neuronal cells. We first showed that olesoxime prevented neurite shrinkage induced by MTAs in differentiated PC-12 and SK-N-SH neuroblastoma cell lines by up to 90%. This neuroprotective effect was correlated with enhanced EB1 accumulation at microtubule plus-ends, increased growth cone microtubule growing rate (20%) and decreased microtubule attenuation duration (54%). The effects of olesoxime on EB comets were specific for differentiated neuronal cells and were not seen either in proliferating neuroblastoma cells, glioblastoma cells or primary endothelial cells. Importantly, olesoxime did not alter MTA cytotoxic properties in a wide range of MTA-sensitive tumor cells, a prerequisite for future clinical application. Finally, olesoxime also counteracted MTA inhibition of microtubule-dependent mitochondria trafficking. These results provide additional insight into the neuroprotective properties of olesoxime, highlighting a role for microtubule dynamics in preservation of neurite architecture and axoplasmic transport, which are both disturbed by MTAs. The neuron-specific protective properties of olesoxime support its further development to treat MTA-induced neuropathy. Copyright 2010 Elsevier Inc. All rights reserved.

  1. 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.

  2. Effectiveness of a selective, personality-targeted prevention program for adolescent alcohol use and misuse: a cluster randomized controlled trial.

    Science.gov (United States)

    Conrod, Patricia J; O'Leary-Barrett, Maeve; Newton, Nicola; Topper, Lauren; Castellanos-Ryan, Natalie; Mackie, Clare; Girard, Alain

    2013-03-01

    Selective school-based alcohol prevention programs targeting youth with personality risk factors for addiction and mental health problems have been found to reduce substance use and misuse in those with elevated personality profiles. To report 24-month outcomes of the Teacher-Delivered Personality-Targeted Interventions for Substance Misuse Trial (Adventure trial) in which school staff were trained to provide interventions to students with 1 of 4 high-risk (HR) profiles: anxiety sensitivity, hopelessness, impulsivity, and sensation seeking and to examine the indirect herd effects of this program on the broader low-risk (LR) population of students who were not selected for intervention. Cluster randomized controlled trial. Secondary schools in London, United Kingdom. A total of 1210 HR and 1433 LR students in the ninth grade (mean [SD] age, 13.7 [0.33] years). Schools were randomized to provide brief personality-targeted interventions to HR youth or treatment as usual (statutory drug education in class). Participants were assessed for drinking, binge drinking, and problem drinking before randomization and at 6-monthly intervals for 2 years. Two-part latent growth models indicated long-term effects of the intervention on drinking rates (β = -0.320, SE = 0.145, P = .03) and binge drinking rates (β = -0.400, SE = 0.179, P = .03) and growth in binge drinking (β = -0.716, SE = 0.274, P = .009) and problem drinking (β = -0.452, SE = 0.193, P = .02) for HR youth. The HR youth were also found to benefit from the interventions during the 24-month follow-up on drinking quantity (β = -0.098, SE = 0.047, P = .04), growth in drinking quantity (β = -0.176, SE = 0.073, P = .02), and growth in binge drinking frequency (β = -0.183, SE = 0.092, P = .047). Some herd effects in LR youth were observed, specifically on drinking rates (β = -0.259, SE = 0.132, P = .049) and growth of binge drinking (β = -0.244, SE = 0.073, P = .001), during the 24-month follow-up. Findings further

  3. 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.

  4. Targeted selected reaction monitoring mass spectrometric immunoassay for insulin-like growth factor 1.

    Directory of Open Access Journals (Sweden)

    Eric E Niederkofler

    Full Text Available Insulin-like growth factor 1 (IGF1 is an important biomarker of human growth disorders that is routinely analyzed in clinical laboratories. Mass spectrometry-based workflows offer a viable alternative to standard IGF1 immunoassays, which utilize various pre-analytical preparation strategies. In this work we developed an assay that incorporates a novel sample preparation method for dissociating IGF1 from its binding proteins. The workflow also includes an immunoaffinity step using antibody-derivatized pipette tips, followed by elution, trypsin digestion, and LC-MS/MS separation and detection of the signature peptides in a selected reaction monitoring (SRM mode. The resulting quantitative mass spectrometric immunoassay (MSIA exhibited good linearity in the range of 1 to 1,500 ng/mL IGF1, intra- and inter-assay precision with CVs of less than 10%, and lowest limits of detection of 1 ng/mL. The linearity and recovery characteristics of the assay were also established, and the new method compared to a commercially available immunoassay using a large cohort of human serum samples. The IGF1 SRM MSIA is well suited for use in clinical laboratories.

  5. Potential targets for selection during the evolution of viviparity in cold-climate reptiles.

    Science.gov (United States)

    Li, Hong; Elphick, Melanie; Shine, Richard

    2017-01-01

    Viviparity (live-bearing) has evolved from oviparity (egg-laying) in more than 100 lineages of squamate reptiles (lizards and snakes). This transition generally has occurred in cool climates, where thermal differentials between eggs in the (cool) nest versus the (warm) maternal oviduct influence embryonic development, in ways that may enhance offspring fitness. To identify specific traits potentially under selection, we incubated eggs of a montane scincid lizard at conditions simulating natural nests, maternal body temperatures, and an intermediate stage (2-week uterine retention of eggs prior to laying). Incubation at maternal temperatures throughout incubation affected the hatchling lizard's activity level and boldness, as well as its developmental rate, morphology, and locomotor ability. A treatment that mimicked the initial stages of the transition toward viviparity had a major effect on some hatchling traits (locomotor speeds), a minor effect on others (tail length, total incubation period) and no effect on yet others (offspring behaviors). More generally, different aspects of the phenotype are sensitive to incubation conditions at different stages of development; thus, the evolution of reptilian viviparity may have been driven by a succession of advantages that accrued at different stages of embryogenesis.

  6. 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.

    2013-01-01

    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. PMID:24190909

  7. 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.

  8. Selection of GalNAc-conjugated siRNAs with limited off-target-driven rat hepatotoxicity.

    Science.gov (United States)

    Janas, Maja M; Schlegel, Mark K; Harbison, Carole E; Yilmaz, Vedat O; Jiang, Yongfeng; Parmar, Rubina; Zlatev, Ivan; Castoreno, Adam; Xu, Huilei; Shulga-Morskaya, Svetlana; Rajeev, Kallanthottathil G; Manoharan, Muthiah; Keirstead, Natalie D; Maier, Martin A; Jadhav, Vasant

    2018-02-19

    Small interfering RNAs (siRNAs) conjugated to a trivalent N-acetylgalactosamine (GalNAc) ligand are being evaluated in investigational clinical studies for a variety of indications. The typical development candidate selection process includes evaluation of the most active compounds for toxicity in rats at pharmacologically exaggerated doses. The subset of GalNAc-siRNAs that show rat hepatotoxicity is not advanced to clinical development. Potential mechanisms of hepatotoxicity can be associated with the intracellular accumulation of oligonucleotides and their metabolites, RNA interference (RNAi)-mediated hybridization-based off-target effects, and/or perturbation of endogenous RNAi pathways. Here we show that rodent hepatotoxicity observed at supratherapeutic exposures can be largely attributed to RNAi-mediated off-target effects, but not chemical modifications or the perturbation of RNAi pathways. Furthermore, these off-target effects can be mitigated by modulating seed-pairing using a thermally destabilizing chemical modification, which significantly improves the safety profile of a GalNAc-siRNA in rat and may minimize the occurrence of hepatotoxic siRNAs across species.

  9. Automatic segmentation of the clinical target volume and organs at risk in the planning CT for rectal cancer using deep dilated convolutional neural networks.

    Science.gov (United States)

    Men, Kuo; Dai, Jianrong; Li, Yexiong

    2017-12-01

    Delineation of the clinical target volume (CTV) and organs at risk (OARs) is very important for radiotherapy but is time-consuming and prone to inter-observer variation. Here, we proposed a novel deep dilated convolutional neural network (DDCNN)-based method for fast and consistent auto-segmentation of these structures. Our DDCNN method was an end-to-end architecture enabling fast training and testing. Specifically, it employed a novel multiple-scale convolutional architecture to extract multiple-scale context features in the early layers, which contain the original information on fine texture and boundaries and which are very useful for accurate auto-segmentation. In addition, it enlarged the receptive fields of dilated convolutions at the end of networks to capture complementary context features. Then, it replaced the fully connected layers with fully convolutional layers to achieve pixel-wise segmentation. We used data from 278 patients with rectal cancer for evaluation. The CTV and OARs were delineated and validated by senior radiation oncologists in the planning computed tomography (CT) images. A total of 218 patients chosen randomly were used for training, and the remaining 60 for validation. The Dice similarity coefficient (DSC) was used to measure segmentation accuracy. Performance was evaluated on segmentation of the CTV and OARs. In addition, the performance of DDCNN was compared with that of U-Net. The proposed DDCNN method outperformed the U-Net for all segmentations, and the average DSC value of DDCNN was 3.8% higher than that of U-Net. Mean DSC values of DDCNN were 87.7% for the CTV, 93.4% for the bladder, 92.1% for the left femoral head, 92.3% for the right femoral head, 65.3% for the intestine, and 61.8% for the colon. The test time was 45 s per patient for segmentation of all the CTV, bladder, left and right femoral heads, colon, and intestine. We also assessed our approaches and results with those in the literature: our system showed superior

  10. 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

  11. 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.

  12. In vitro selection, characterization, and biosensing application of high-affinity cylindrospermopsin-targeting aptamers.

    Science.gov (United States)

    Elshafey, Reda; Siaj, Mohamed; Zourob, Mohammed

    2014-09-16

    Contamination of freshwater with cyanotoxin cylindrospermopsin (CYN) represents a significant global concern for public health. The sensitive detection of CYN is necessary to effectively manage and control the treatment of water resources. Here we report a novel, highly sensitive label-free aptasensor for CYN analysis, using aptamers as specific receptors. We have selected the DNA aptamers from a diverse random library using the in vitro screening SELEX approach. The aptamers exhibited high affinity for CYN with Kd of nanomolar range. One aptamer exhibited conformational change upon CYN recognition (CD analysis) and was used to fabricate the label-free impedimetric aptasensor for CYN. A self-assembled monolayer from a disulfide-derivatized aptamer was formed on a gold electrode to fabricate the aptasensor. Upon CYN capturing to the aptasensor surface, a marked drop in the electron transfer resistance was obtained, which was used as the principle of detection of CYN. This resulted from the aptamer's conformational change induced by CYN recognition. The present aptasensor could detect CYN with the limit of detection as low as 100 pM and a wide linear range of 0.1 to 80 nM. When mounted on the gold surface, the aptamer exhibited a lower dissociation constant for CYN than that observed in the fluorescence assay, implying that the anchoring of the aptamer on the Au surface improved its affinity to CYN. Moreover, the aptasensor showed high specificity toward other coexistent cyanobacterial toxins of microcystin-LR and Anatoxin-a. Further biosensor designs will be generated using those aptamers for simple and sensitive CYN monitoring.

  13. Impact of sleep inertia on visual selective attention for rare targets and the influence of chronotype.

    Science.gov (United States)

    Ritchie, Hannah K; Burke, Tina M; Dear, Tristan B; Mchill, Andrew W; Axelsson, John; Wright, Kenneth P

    2017-10-01

    Sleep inertia is affected by circadian phase, with worse performance upon awakening from sleep during the biological night than biological day. Visual search/selective visual attention performance is known to be sensitive to sleep inertia and circadian phase. Individual differences exist in the circadian timing of habitual wake time, which may contribute to individual differences in sleep inertia. Because later chronotypes awaken at an earlier circadian phase, we hypothesized that later chronotypes would have worse visual search performance during sleep inertia than earlier chronotypes if awakened at habitual wake time. We analysed performance from 18 healthy participants [five females (22.1 ± 3.7 years; mean ± SD)] at ~1, 10, 20, 30, 40 and 60 min following electroencephalogram-verified awakening from an 8 h in-laboratory sleep opportunity. Cognitive throughput and reaction times of correct responses were impaired by sleep inertia and took ~10-30 min to improve after awakening. Regardless whether chronotype was defined by dim light melatonin onset or mid-sleep clock hour on free days, derived from the Munich ChronoType Questionnaire, the duration of sleep inertia for cognitive throughput and reaction times was longer for later chronotypes (n = 7) compared with earlier chronotypes (n = 7). Specifically, performance for earlier chronotypes showed significant improvement within ~10-20 min after awakening, whereas performance for later chronotypes took ~30 min or longer to show significant improvement (P sleep, and are consistent with circadian theory suggesting that sleep inertia contributes to longer-lasting impairments in morning performance in later chronotypes. © 2017 European Sleep Research Society.

  14. High Level of Nonsynonymous Changes in Common Bean Suggests That Selection under Domestication Increased Functional Diversity at Target Traits.

    Science.gov (United States)

    Bitocchi, Elena; Rau, Domenico; Benazzo, Andrea; Bellucci, Elisa; Goretti, Daniela; Biagetti, Eleonora; Panziera, Alex; Laidò, Giovanni; Rodriguez, Monica; Gioia, Tania; Attene, Giovanna; McClean, Phillip; Lee, Rian K; Jackson, Scott A; Bertorelle, Giorgio; Papa, Roberto

    2016-01-01

    Crop species have been deeply affected by the domestication process, and there have been many efforts to identify selection signatures at the genome level. This knowledge will help geneticists to better understand the evolution of organisms, and at the same time, help breeders to implement successful breeding strategies. Here, we focused on domestication in the Mesoamerican gene pool of Phaseolus vulgaris by sequencing 49 gene fragments from a sample of 45 P. vulgaris wild and domesticated accessions, and as controls, two accessions each of the closely related species Phaseolus coccineus and Phaseolus dumosus . An excess of nonsynonymous mutations within the domesticated germplasm was found. Our data suggest that the cost of domestication alone cannot explain fully this finding. Indeed, the significantly higher frequency of polymorphisms in the coding regions observed only in the domesticated plants (compared to noncoding regions), the fact that these mutations were mostly nonsynonymous and appear to be recently derived mutations, and the investigations into the functions of their relative genes (responses to biotic and abiotic stresses), support a scenario that involves new functional mutations selected for adaptation during domestication. Moreover, consistent with this hypothesis, selection analysis and the possibility to compare data obtained for the same genes in different studies of varying sizes, data types, and methodologies allowed us to identify four genes that were strongly selected during domestication. Each selection candidate is involved in plant resistance/tolerance to abiotic stresses, such as heat, drought, and salinity. Overall, our study suggests that domestication acted to increase functional diversity at target loci, which probably controlled traits related to expansion and adaptation to new agro-ecological growing conditions.

  15. Speech-language pathologists' practices regarding assessment, analysis, target selection, intervention, and service delivery for children with speech sound disorders.

    Science.gov (United States)

    Mcleod, Sharynne; Baker, Elise

    2014-01-01

    A survey of 231 Australian speech-language pathologists (SLPs) was undertaken to describe practices regarding assessment, analysis, target selection, intervention, and service delivery for children with speech sound disorders (SSD). The participants typically worked in private practice, education, or community health settings and 67.6% had a waiting list for services. For each child, most of the SLPs spent 10-40 min in pre-assessment activities, 30-60 min undertaking face-to-face assessments, and 30-60 min completing paperwork after assessments. During an assessment SLPs typically conducted a parent interview, single-word speech sampling, collected a connected speech sample, and used informal tests. They also determined children's stimulability and estimated intelligibility. With multilingual children, informal assessment procedures and English-only tests were commonly used and SLPs relied on family members or interpreters to assist. Common analysis techniques included determination of phonological processes, substitutions-omissions-distortions-additions (SODA), and phonetic inventory. Participants placed high priority on selecting target sounds that were stimulable, early developing, and in error across all word positions and 60.3% felt very confident or confident selecting an appropriate intervention approach. Eight intervention approaches were frequently used: auditory discrimination, minimal pairs, cued articulation, phonological awareness, traditional articulation therapy, auditory bombardment, Nuffield Centre Dyspraxia Programme, and core vocabulary. Children typically received individual therapy with an SLP in a clinic setting. Parents often observed and participated in sessions and SLPs typically included siblings and grandparents in intervention sessions. Parent training and home programs were more frequently used than the group therapy. Two-thirds kept up-to-date by reading journal articles monthly or every 6 months. There were many similarities with

  16. Dual display: phage selection driven by co-engagement of two targets by two different antibody fragments.

    Science.gov (United States)

    Fagète, Séverine; Botas-Perez, Ledicia; Rossito-Borlat, Irène; Adea, Kenneth; Gueneau, Franck; Ravn, Ulla; Rousseau, François; Kosco-Vilbois, Marie; Fischer, Nicolas; Hartley, Oliver

    2017-09-01

    Antibody phage display technology has supported the emergence of numerous therapeutic antibodies. The development of bispecific antibodies, a promising new frontier in antibody therapy, could be facilitated by new phage display approaches that enable pairs of antibodies to be co-selected based on co-engagement of their respective targets. We describe such an approach, making use of two complementary leucine zipper domains that heterodimerize with high affinity. Phagemids encoding a first antibody fragment (scFv) fused to phage coat protein via the first leucine zipper are rescued in bacteria expressing a second scFv fused to the second leucine zipper as a soluble periplasmic protein, so that it is acquired by phage during assembly. Using a soluble scFv specific for a human CD3-derived peptide, we show that its acquisition by phage displaying an irrelevant antibody is sufficiently robust to drive selection of rare phage (1 in 105) over three rounds of panning. We then set up a model selection experiment using a cell line expressing the chemokine receptor CCR5 fused to the CD3 peptide together with a panel of phage clones capable displaying either an anti-CCR5 scFv or an irrelevant antibody, with or without the capacity to acquire the soluble anti-CD3 scFv. In this experiment we showed that rare phage (1 in 105) capable of displaying the two different scFvs can be specifically enriched over four rounds of panning. This approach has the potential to be applied to the identification of pairs of ligands capable of co-engaging two different user-defined targets, which would facilitate the discovery of novel bispecific antibodies. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  17. Automatic sample changers maintenance manual

    International Nuclear Information System (INIS)

    Myers, T.A.

    1978-10-01

    This manual describes and provides trouble-shooting aids for the Automatic Sample Changer electronics on the automatic beta counting system, developed by the Los Alamos Scientific Laboratory Group CNC-11. The output of a gas detector is shaped by a preamplifier, then is coupled to an amplifier. Amplifier output is discriminated and is the input to a scaler. An identification number is associated with each sample. At a predetermined count length, the identification number, scaler data plus other information is punched out on a data card. The next sample to be counted is automatically selected. The beta counter uses the same electronics as the prior count did, the only difference being the sample identification number and sample itself. This manual is intended as a step-by-step aid in trouble-shooting the electronics associated with positioning the sample, counting the sample, and getting the needed data punched on an 80-column data card

  18. Ligand-Directed Functional Selectivity at the Mu Opioid Receptor Revealed by Label-Free Integrative Pharmacology On-Target

    Science.gov (United States)

    Morse, Megan; Tran, Elizabeth; Sun, Haiyan; Levenson, Robert; Fang, Ye

    2011-01-01

    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. PMID:22003401

  19. Data structures and target classification; Proceedings of the Meeting, Orlando, FL, Apr. 1, 2, 1991

    Science.gov (United States)

    Libby, Vibeke

    1991-08-01

    The present conference discusses topics in multisensor fusion and signal processing, data structures in distributed environments, computational methods and architectures, and automatic target recognition. Attention is given to the adaptive selection of sensors, multisensor imagery fusion based on target motion, multisensor imaging technology for airborne surveillance, optimal topology communications networks, scanning strategies for target detection, VLSI fuzzy-logic controller design, an optical pattern recognizer, radar-based target recognition techniques, and algorithms for radar clutter statistical classification.

  20. 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

  1. Peptide-modified liposomes for selective targeting of bombesin receptors overexpressed by cancer cells: a potential theranostic agent

    Science.gov (United States)

    Accardo, Antonella; Salsano, Giuseppina; Morisco, Anna; Aurilio, Michela; Parisi, Antonio; Maione, Francesco; Cicala, Carla; Tesauro, Diego; Aloj, Luigi; De Rosa, Giuseppe; Morelli, Giancarlo

    2012-01-01

    Objectives Drug delivery systems consisting of liposomes displaying a cell surface receptor-targeting peptide are being developed to specifically deliver chemotherapeutic drugs to tumors overexpressing a target receptor. This study addresses novel liposome composition approaches to specifically target tissues overexpressing bombesin (BN) receptors. Methods A new amphiphilic peptide derivative (MonY-BN) containing the BN(7–14) peptide, the DTPA (diethylenetriaminepentaacetate) chelating agent, a hydrophobic moiety with two C18 alkyl chains, and polyethylene glycol spacers, has been synthesized by solid-phase methods. Liposomes have been generated by co-aggregation of MonY-BN with 1,2-distearoyl-sn-glycero-3-phosphocholine (DSPC). The structural and biological properties of these new target-selective drug-delivery systems have been characterized. Results Liposomes with a DSPC/MonY-BN (97/3 molar ratio) composition showed a diameter of 145.5 ± 31.5 nm and a polydispersity index of 0.20 ± 0.05. High doxorubicin (Dox) loading was obtained with the remote pH gradient method using citrate as the inner buffer. Specific binding to PC-3 cells of DSPC/MonY-BN liposomes was obtained (2.7% ± 0.3%, at 37°C), compared with peptide-free DSPC liposomes (1.4% ± 0.2% at 37°C). Incubation of cells with DSPC/ MonY-BN/Dox showed significantly lower cell survival compared with DSPC/Dox-treated cells, in the presence of 100 ng/mL and 300 ng/mL drug amounts, in cytotoxicity experiments. Intravenous treatment of PC-3 xenograft-bearing mice with DSPC/MonY-BN/Dox at 10 mg/kg Dox dose produced higher tumour growth inhibition (60%) compared with nonspecific DSPC/ Dox liposomes (36%) relative to control animals. Conclusion The structural and loading properties of DSPC/MonY-BN liposomes along with the observed in-vitro and in-vivo activity are encouraging for further development of this approach for target-specific cancer chemotherapy. PMID:22619538

  2. Automatic fluid dispenser

    Science.gov (United States)

    Sakellaris, P. C. (Inventor)

    1977-01-01

    Fluid automatically flows to individual dispensing units at predetermined times from a fluid supply and is available only for a predetermined interval of time after which an automatic control causes the fluid to drain from the individual dispensing units. Fluid deprivation continues until the beginning of a new cycle when the fluid is once again automatically made available at the individual dispensing units.

  3. Development and application of an automatic tool for the selection of control variables based on the self-optimizing control methodology

    Directory of Open Access Journals (Sweden)

    S. K. Silva

    Full Text Available Abstract Rules for control structure design for industrial processes have been extensively proposed in the literature. Some model-based methodologies have a sound mathematical basis, such as the self-optimizing control technology. The procedure can be applied with the aid of available commercial simulators, e.g., PRO/IITM and AspenPlus®, from which the converging results are obtained more suitably for industrial applications, lessening the effort needed to build an appropriate mathematical model of the plant. Motivated by this context, this work explores the development and application of a tool designed to automatically generate near-optimal controlled structures for process plants based on the self-optimizing control technology. The goal is to provide a means to facilitate the way possible arrangements of controlled variables are generated. Using the local minimum singular value rule supported by a modified version of a branch-and-bound algorithm, the best sets of candidate controlled variables can be identified that minimize the loss between real optimal operation and operation under constant set-point policy. A case study consisting of a deethanizer is considered to show the main features of the proposed tool. The conclusion indicates the feasibility of merging complex theoretical contents within the framework of a user-friendly interface simple enough to generate control structures suitable for real world implementation.

  4. Mesoscale Assessment of CO2 Storage Potential and Geological Suitability for Target Area Selection in the Sichuan Basin

    Directory of Open Access Journals (Sweden)

    Yujie Diao

    2017-01-01

    Full Text Available In China, south of the Yangtze River, there are a large number of carbon sources, while the Sichuan Basin is the largest sedimentary basin; it makes sense to select the targets for CO2 geological storage (CGUS early demonstration. For CO2 enhanced oil and gas, coal bed methane recovery (CO2-EOR, EGR, and ECBM, or storage in these depleted fields, the existing oil, gas fields, or coal seams could be the target areas in the mesoscale. This paper proposed a methodology of GIS superimposed multisource information assessment of geological suitability for CO2 enhanced water recovery (CO2-EWR or only storage in deep saline aquifers. The potential per unit area of deep saline aquifers CO2 storage in Central Sichuan is generally greater than 50 × 104 t/km2 at P50 probability level, with Xujiahe group being the main reservoir. CO2 storage potential of depleted gas fields is 53.73 × 108 t, while it is 33.85 × 108 t by using CO2-EGR technology. This paper recommended that early implementation of CGUS could be carried out in the deep saline aquifers and depleted gas fields in the Sichuan Basin, especially that of the latter because of excellent traps, rich geological data, and well-run infrastructures.

  5. Practices to optimise gastrointestinal nematode control on sheep, goat and cattle farms in Europe using targeted (selective) treatments.

    Science.gov (United States)

    Charlier, J; Morgan, E R; Rinaldi, L; van Dijk, J; Demeler, J; Höglund, J; Hertzberg, H; Van Ranst, B; Hendrickx, G; Vercruysse, J; Kenyon, F

    2014-09-13

    Due to the development of anthelmintic resistance, there have been calls for more sustainable nematode control practices. Two important concepts were introduced to study and promote the sustainable use of anthelmintics: targeted treatments (TT), where the whole flock/herd is treated based on knowledge of the risk, or parameters that quantify the severity of infection; and targeted selective treatments (TST), where only individual animals within the grazing group are treated. The aim of the TT and TST approaches is to effectively control nematode-induced production impacts while preserving anthelmintic efficacy by maintaining a pool of untreated parasites in refugia. Here, we provide an overview of recent studies that assess the use of TT/TST against gastrointestinal nematodes in ruminants and investigate the economic consequences, feasibility and knowledge gaps associated with TST. We conclude that TT/TST approaches are ready to be used and provide practical benefits today. However, a major shift in mentality will be required to make these approaches common practice in parasite control. British Veterinary Association.

  6. Managing anthelmintic resistance-Variability in the dose of drug reaching the target worms influences selection for resistance?

    Science.gov (United States)

    Leathwick, Dave M; Luo, Dongwen

    2017-08-30

    The concentration profile of anthelmintic reaching the target worms in the host can vary between animals even when administered doses are tailored to individual liveweight at the manufacturer's recommended rate. Factors contributing to variation in drug concentration include weather, breed of animal, formulation and the route by which drugs are administered. The implications of this variability for the development of anthelmintic resistance was investigated using Monte-Carlo simulation. A model framework was established where 100 animals each received a single drug treatment. The 'dose' of drug allocated to each animal (i.e. the concentration-time profile of drug reaching the target worms) was sampled at random from a distribution of doses with mean m and standard deviation s. For each animal the dose of drug was used in conjunction with pre-determined dose-response relationships, representing single and poly-genetic inheritance, to calculate efficacy against susceptible and resistant genotypes. These data were then used to calculate the overall change in resistance gene frequency for the worm population as a result of the treatment. Values for m and s were varied to reflect differences in both mean dose and the variability in dose, and for each combination of these 100,000 simulations were run. The resistance gene frequency in the population after treatment increased as m decreased and as s increased. This occurred for both single and poly-gene models and for different levels of dominance (survival under treatment) of the heterozygote genotype(s). The results indicate that factors which result in lower and/or more variable concentrations of active reaching the target worms are more likely to select for resistance. The potential of different routes of anthelmintic administration to play a role in the development of anthelmintic resistance is discussed. Copyright © 2017 Elsevier B.V. All rights reserved.

  7. Cascaded automatic target recognition (Cascaded ATR)

    Science.gov (United States)

    Walls, Bradley

    2010-04-01

    The global war on terror has plunged US and coalition forces into a battle space requiring the continuous adaptation of tactics and technologies to cope with an elusive enemy. As a result, technologies that enhance the intelligence, surveillance, and reconnaissance (ISR) mission making the warfighter more effective are experiencing increased interest. In this paper we show how a new generation of smart cameras built around foveated sensing makes possible a powerful ISR technique termed Cascaded ATR. Foveated sensing is an innovative optical concept in which a single aperture captures two distinct fields of view. In Cascaded ATR, foveated sensing is used to provide a coarse resolution, persistent surveillance, wide field of view (WFOV) detector to accomplish detection level perception. At the same time, within the foveated sensor, these detection locations are passed as a cue to a steerable, high fidelity, narrow field of view (NFOV) detector to perform recognition level perception. Two new ISR mission scenarios, utilizing Cascaded ATR, are proposed.

  8. Selective RNA targeting and regulated signaling by RIG-I is controlled by coordination of RNA and ATP binding.

    Science.gov (United States)

    Fitzgerald, Megan E; Rawling, David C; Potapova, Olga; Ren, Xiaoming; Kohlway, Andrew; Pyle, Anna Marie

    2017-02-17

    RIG-I is an innate immune receptor that detects and responds to infection by deadly RNA viruses such as influenza, and Hepatitis C. In the cytoplasm, RIG-I is faced with a difficult challenge: it must sensitively detect viral RNA while ignoring the abundance of host RNA. It has been suggested that RIG-I has a ‘proof-reading’ mechanism for rejecting host RNA targets, and that disruptions of this selectivity filter give rise to autoimmune diseases. Here, we directly monitor RNA proof-reading by RIG-I and we show that it is controlled by a set of conserved amino acids that couple RNA and ATP binding to the protein (Motif III). Mutations of this motif directly modulate proof-reading by eliminating or enhancing selectivity for viral RNA, with major implications for autoimmune disease and cancer. More broadly, the results provide a physical explanation for the ATP-gated behavior of SF2 RNA helicases and receptor proteins.

  9. Performance evaluation of structure based and ligand based virtual screening methods on ten selected anti-cancer targets.

    Science.gov (United States)

    Ramasamy, Thilagavathi; Selvam, Chelliah

    2015-10-15

    Virtual screening has become an important tool in drug discovery process. Structure based and ligand based approaches are generally used in virtual screening process. To date, several benchmark sets for evaluating the performance of the virtual screening tool are available. In this study, our aim is to compare the performance of both structure based and ligand based virtual screening methods. Ten anti-cancer targets and their corresponding benchmark sets from 'Demanding Evaluation Kits for Objective In silico Screening' (DEKOIS) library were selected. X-ray crystal structures of protein-ligand complexes were selected based on their resolution. Openeye tools such as FRED, vROCS were used and the results were carefully analyzed. At EF1%, vROCS produced better results but at EF5% and EF10%, both FRED and ROCS produced almost similar results. It was noticed that the enrichment factor values were decreased while going from EF1% to EF5% and EF10% in many cases. Published by Elsevier Ltd.

  10. Selective targeting of tumour neovasculature by a radiohalogenated human antibody fragment specific for the ED-B domain of fibronectin

    International Nuclear Information System (INIS)

    Demartis, S.; Tarli, L.; Neri, D.; Borsi, L.; Zardi, L.

    2001-01-01

    Angiogenesis is a characteristic feature of many aggressive tumours and other disorders. Antibodies capable of binding to new blood vessels, but not to mature vessels, could be used as selective targeting agents for immunoscintigraphic and radioimmunotherapeutic applications. Here we show that scFv(L19), a recombinant human antibody fragment with sub-nanomolar affinity for the ED-B domain of fibronectin, a marker of angiogenesis, can be stably labelled with iodine-125 and astatine-211 with full retention of immunoreactivity, using a trimethyl-stannyl benzoate bifunctional derivative. Biodistribution studies in mice bearing two different types of tumour grafted subcutaneously, followed by ex vivo micro-autoradiographic analysis, revealed that scFv(L19) rapidly localises around tumour blood vessels, but not around normal vessels. Four hours after intravenous injection of the stably radioiodinated scFv(L19), tumour to blood ratios were 6:1 in mice bearing the F9 murine teratocarcinoma and 9:1 in mice bearing an FE8 rat sarcoma. As expected, all other organs (including kidney) contained significantly less radioactivity than the tumour. Since the ED-B domain of fibronectin has an identical sequence in mouse and man, scFv(L19) is a pan-species antibody and the results presented here suggest clinical utility of radiolabelled scFv(L19) for the scintigraphic detection of angiogenesis in vivo. Furthermore, it should now be possible to investigate scFv(L19) for the selective delivery of 211 At to the tumour neovasculature, causing the selective death of tumour endothelial cells and tumour collapse. (orig.)

  11. 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.

  12. An approach to the construction of tailor-made amphiphilic peptides that strongly and selectively bind to hairpin RNA targets.

    Science.gov (United States)

    Lee, Su Jin; Hyun, Soonsil; Kieft, Jeffrey S; Yu, Jaehoon

    2009-02-18

    strategies that can be used to prepare peptides that both strongly and selectively target hairpin RNAs. Specifically, the findings indicate that tailor-made amphiphilic peptide ligands against certain hairpin RNAs can be obtained if the RNA target possesses a deep groove in which both the hydrophobic and hydrophilic spheres of the peptide interact.

  13. 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.

  14. 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. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  15. 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.

    2011-01-01

    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. PMID:20410378

  16. Revealing kinetics and state-dependent binding properties of IKur-targeting drugs that maximize atrial fibrillation selectivity

    Science.gov (United States)

    Ellinwood, Nicholas; Dobrev, Dobromir; Morotti, Stefano; Grandi, Eleonora

    2017-09-01

    The KV1.5 potassium channel, which underlies the ultra-rapid delayed-rectifier current (IKur) and is predominantly expressed in atria vs. ventricles, has emerged as a promising target to treat atrial fibrillation (AF). However, while numerous KV1.5-selective compounds have been screened, characterized, and tested in various animal models of AF, evidence of antiarrhythmic efficacy in humans is still lacking. Moreover, current guidelines for pre-clinical assessment of candidate drugs heavily rely on steady-state concentration-response curves or IC50 values, which can overlook adverse cardiotoxic effects. We sought to investigate the effects of kinetics and state-dependent binding of IKur-targeting drugs on atrial electrophysiology in silico and reveal the ideal properties of IKur blockers that maximize anti-AF efficacy and minimize pro-arrhythmic risk. To this aim, we developed a new Markov model of IKur that describes KV1.5 gating based on experimental voltage-clamp data in atrial myocytes from patient right-atrial samples in normal sinus rhythm. We extended the IKur formulation to account for state-specificity and kinetics of KV1.5-drug interactions and incorporated it into our human atrial cell model. We simulated 1- and 3-Hz pacing protocols in drug-free conditions and with a [drug] equal to the IC50 value. The effects of binding and unbinding kinetics were determined by examining permutations of the forward (kon) and reverse (koff) binding rates to the closed, open, and inactivated states of the KV1.5 channel. We identified a subset of ideal drugs exhibiting anti-AF electrophysiological parameter changes at fast pacing rates (effective refractory period prolongation), while having little effect on normal sinus rhythm (limited action potential prolongation). Our results highlight that accurately accounting for channel interactions with drugs, including kinetics and state-dependent binding, is critical for developing safer and more effective pharmacological anti

  17. 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

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

    Directory of Open Access Journals (Sweden)

    Rebecca J Lawton

    Full Text Available 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

  19. Mid-season targeted selective anthelmintic treatment based on flexible weight gain threshold for nematode infection control in dairy calves.

    Science.gov (United States)

    Merlin, A; Ravinet, N; Madouasse, A; Bareille, N; Chauvin, A; Chartier, C

    2017-10-09

    The suitability of a single mid-season targeted selective treatment (TST) for gastrointestinal nematodes control, based on flexible average daily weight gain (ADWG) thresholds, was investigated in 23 groups of first grazing season calves. In each group, animals were weighed three times: before turnout, at mid-season and at housing. Just after the first weighing, each group was divided in two homogenous sub-groups in terms of age, breed and weight, and randomly allocated to one of two sub-groups intented for two different mid-season anthelmintic treatment strategies: (1) a treatment of all calves composing the sub-group (whole-group treatment (WT)) or (2) a targeted selective weight gain-based treatment (TST) of the animals showing an individual pre-treatment ADWG inferior to the mean pre-treatment ADWG of the corresponding WT sub-group. Anthelmintic treatment (levamisole 7.5 mg/kg BW) was performed 3 to 4 months after turnout. At housing, two parasitological parameters (the anti-Ostertagia ostertagi antibody level-Ostertagia optical density ratio (ODR) and the pepsinogen level) and a clinical parameter (the breech soiling score) were assessed at individual level in each group. Then, the high exposed groups to gastrointestinal nematode (GIN) were defined as groups for which untreated animals exhibited a mean Ostertagia ODR ⩾0.7 and among these groups, the ones characterized by high abomasal damage due to Ostertagia for which untreated animals exhibited a mean pepsinogen level ⩾2.5 U Tyr were also identified. Among TST sub-groups, the treatment ADWG thresholds varied from 338 to 941 g/day and the percentage of treated animals from 28% to 75%. Pre- and post-treatment ADWG as well as parasitological and clinical parameters measured at housing were similar between TST and WT sub-groups including the 17 high exposed groups to GIN. Within these 17 groups, the treatment allowed to significantly improve post-treatment ADWG compared with untreated animals. In the six

  20. A BAND SELECTION METHOD FOR SUB-PIXEL TARGET DETECTION IN HYPERSPECTRAL IMAGES BASED ON LABORATORY AND FIELD REFLECTANCE SPECTRAL COMPARISON

    Directory of Open Access Journals (Sweden)

    S. Sharifi hashjin

    2016-06-01

    Full Text Available In recent years, developing target detection algorithms has received growing interest in hyperspectral images. In comparison to the classification field, few studies have been done on dimension reduction or band selection for target detection in hyperspectral images. This study presents a simple method to remove bad bands from the images in a supervised manner for sub-pixel target detection. The proposed method is based on comparing field and laboratory spectra of the target of interest for detecting bad bands. For evaluation, the target detection blind test dataset is used in this study. Experimental results show that the proposed method can improve efficiency of the two well-known target detection methods, ACE and CEM.

  1. ANALYSIS OF EXISTING AND PROSPECTIVE TECHNICAL CONTROL SYSTEMS OF NUMERIC CODES AUTOMATIC BLOCKING

    Directory of Open Access Journals (Sweden)

    A. M. Beznarytnyy

    2013-09-01

    Full Text Available Purpose. To identify the characteristic features of the engineering control measures system of automatic block of numeric code, identifying their advantages and disadvantages, to analyze the possibility of their use in the problems of diagnosing status of the devices automatic block and setting targets for the development of new diagnostic systems. Methodology. In order to achieve targets the objective theoretical and analytical method and the method of functional analysis have been used. Findings. The analysis of existing and future facilities of the remote control and diagnostics automatic block devices had shown that the existing systems of diagnosis were not sufficiently informative, designed primarily to control the discrete parameters, which in turn did not allow them to construct a decision support subsystem. In developing of new systems of technical diagnostics it was proposed to use the principle of centralized distributed processing of diagnostic data, to include a subsystem support decision-making in to the diagnostics system, it will reduce the amount of work to maintain the devices blocking and reduce recovery time after the occurrence injury. Originality. As a result, the currently existing engineering controls facilities of automatic block can not provide a full assessment of the state distillation alarms and locks. Criteria for the development of new systems of technical diagnostics with increasing amounts of diagnostic information and its automatic analysis were proposed. Practical value. These results of the analysis can be used in practice in order to select the technical control of automatic block devices, as well as the further development of diagnostic systems automatic block that allows for a gradual transition from a planned preventive maintenance service model to the actual state of the monitored devices.

  2. Suppress orthotopic colon cancer and its metastasis through exact targeting and highly selective drug release by a smart nanomicelle.

    Science.gov (United States)

    Zhu, Chunqi; Zhang, Hanbo; Li, Wei; Luo, Lihua; Guo, Xiaomeng; Wang, Zuhua; Kong, Fenfen; Li, Qingpo; Yang, Jie; Du, Yongzhong; You, Jian

    2018-04-01

    The treatment of metastatic cancer is a huge challenge at the moment. Highly precise targeting delivery and drug release in tumor have always been our pursuit in cancer therapy, especially to advance cancer with metastasis, for increasing the efficacy and biosafety. We established a smart nanosized micelle, formed by tocopherol succinate (TOS) conjugated hyaluronic acid (HA) using a disulfide bond linker. The micelle (HA-SS-TOS, HSST) can highly specifically bind with CD44 receptor over-expressed tumor, and response selectively to high GSH level in the cells, inducing disulfide bond breakage and the release of the payload (paclitaxel, PTX). To predict the antitumor efficacy of the micelles more clinically, we established an orthotopic colon cancer model with high metastasis rate, which could be visualized by the luciferase bioluminescence. Our data confirmed CD44 high expression in the colon cancer cells. Highly matching between the micellar fluorescence and bioluminescence of cancer cells in intestines demonstrated an exact recognition of our micelles to orthotopic colon tumor and its metastatic cells, attributing to the mediation of CD44 receptors. Furthermore, the fluorescence of the released Nile Red from the micelles was found only in the tumor and its metastatic cells, and almost completely overlapped with the bioluminescence of the cancer cells, indicating a highly selective drug release. Our micelles presented an excellent therapeutic effect against metastatic colon cancer, and induced significantly prolonged survival time for the mice, which might become a promising nanomedicine platform for the future clinical application against advanced cancers with high CD44 receptor expression. Copyright © 2018 Elsevier Ltd. All rights reserved.

  3. 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.)

  4. First- and Second-Line Targeted Systemic Therapy in Hepatocellular Carcinoma—An Update on Patient Selection and Response Evaluation

    Directory of Open Access Journals (Sweden)

    Johann von Felden

    2016-11-01

    Full Text Available Advanced hepatocellular carcinoma (HCC with vascular invasion and/or extrahepatic spread and preserved liver function, according to stage C of the Barcelona Clinic Liver Cancer (BCLC classification, has a dismal prognosis. The multi-targeted tyrosine-kinase receptor inhibitor (TKI sorafenib is the only proven active substance in systemic HCC therapy for first-line treatment. In this review, we summarize current aspects in patient selection and management of side effects, and provide an update on response evaluation during first-line sorafenib therapy. Since second-line treatment options have been improved with the successful completion of the RESORCE trial, demonstrating a survival benefit for second-line treatment with the TKI regorafenib, response monitoring during first-line therapy will be critical to deliver optimal systemic therapy in HCC. To this regard, specific side effects, in particular worsening of arterial hypertension and diarrhea, might suggest treatment response during first-line sorafenib therapy; however, clear predictive clinical markers, as well as laboratory test or serum markers, are not established. Assessment of radiologic response according to the modified Response Evaluation Criteria in Solid Tumors (mRECIST is helpful to identify patients who do not benefit from sorafenib treatment.

  5. Selective BCL-2 inhibition by ABT-199 causes on-target cell death in acute myeloid leukemia.

    Science.gov (United States)

    Pan, Rongqing; Hogdal, Leah J; Benito, Juliana M; Bucci, Donna; Han, Lina; Borthakur, Gautam; Cortes, Jorge; DeAngelo, Daniel J; Debose, Lakeisha; Mu, Hong; Döhner, Hartmut; Gaidzik, Verena I; Galinsky, Ilene; Golfman, Leonard S; Haferlach, Torsten; Harutyunyan, Karine G; Hu, Jianhua; Leverson, Joel D; Marcucci, Guido; Müschen, Markus; Newman, Rachel; Park, Eugene; Ruvolo, Peter P; Ruvolo, Vivian; Ryan, Jeremy; Schindela, Sonja; Zweidler-McKay, Patrick; Stone, Richard M; Kantarjian, Hagop; Andreeff, Michael; Konopleva, Marina; Letai, Anthony G

    2014-03-01

    B-cell leukemia/lymphoma 2 (BCL-2) prevents commitment to programmed cell death at the mitochondrion. It remains a challenge to identify those tumors that are best treated by inhibition of BCL-2. Here, we demonstrate that acute myeloid leukemia (AML) cell lines, primary patient samples, and murine primary xenografts are very sensitive to treatment with the selective BCL-2 antagonist ABT-199. In primary patient cells, the median IC50 was approximately 10 nmol/L, and cell death occurred within 2 hours. Our ex vivo sensitivity results compare favorably with those observed for chronic lymphocytic leukemia, a disease for which ABT-199 has demonstrated consistent activity in clinical trials. Moreover, mitochondrial studies using BH3 profiling demonstrate activity at the mitochondrion that correlates well with cytotoxicity, supporting an on-target mitochondrial mechanism of action. Our protein and BH3 profiling studies provide promising tools that can be tested as predictive biomarkers in any clinical trial of ABT-199 in AML.

  6. In Silico Screening, Structure-Activity Relationship, and Biologic Evaluation of Selective Pteridine Reductase Inhibitors Targeting Visceral Leishmaniasis▿ †

    Science.gov (United States)

    Kaur, Jaspreet; Kumar, Pranav; Tyagi, Sargam; Pathak, Richa; Batra, Sanjay; Singh, Prashant; Singh, Neeloo

    2011-01-01

    In this study we utilized the concept of rational drug design to identify novel compounds with optimal selectivity, efficacy and safety, which would bind to the target enzyme pteridine reductase 1 (PTR1) in Leishmania parasites. Twelve compounds afforded from Baylis-Hillman chemistry were docked by using the QUANTUM program into the active site of Leishmania donovani PTR1 homology model. The biological activity for these compounds was estimated in green fluorescent protein-transfected L. donovani promastigotes, and the most potential analogue was further investigated in intracellular amastigotes. Structure-activity relationship based on homology model drawn on our recombinant enzyme was substantiated by recombinant enzyme inhibition assay and growth of the cell culture. Flow cytometry results indicated that 7-(4-chlorobenzyl)-3-methyl-4-(4-trifluoromethyl-phenyl)-3,4,6,7,8,9-hexahydro-pyrimido[1,2-a]pyrimidin-2-one (compound 7) was 10 times more active on L. donovani amastigotes (50% inhibitory concentration [IC50] = 3 μM) than on promastigotes (IC50 = 29 μM). Compound 7 exhibited a Ki value of 0.72 μM in a recombinant enzyme inhibition assay. We discovered that novel pyrimido[1,2-a]pyrimidin-2-one systems generated from the allyl amines afforded from the Baylis-Hillman acetates could have potential as a valuable pharmacological tool against the neglected disease visceral leishmaniasis. PMID:21115787

  7. Non-targeted detection of chemical contamination in carbonated soft drinks using NMR spectroscopy, variable selection and chemometrics.

    Science.gov (United States)

    Charlton, Adrian J; Robb, Paul; Donarski, James A; Godward, John

    2008-06-23

    An efficient method for detecting malicious and accidental contamination of foods has been developed using a combined 1H nuclear magnetic resonance (NMR) and chemometrics approach. The method has been demonstrated using a commercially available carbonated soft drink, as being capable of identifying atypical products and to identify contaminant resonances. Soft-independent modelling of class analogy (SIMCA) was used to compare 1H NMR profiles of genuine products (obtained from the manufacturer) against retail products spiked in the laboratory with impurities. The benefits of using feature selection for extracting contaminant NMR frequencies were also assessed. Using example impurities (paraquat, p-cresol and glyphosate) NMR spectra were analysed using multivariate methods resulting in detection limits of approximately 0.075, 0.2, and 0.06 mM for p-cresol, paraquat and glyphosate, respectively. These detection limits are shown to be approximately 100-fold lower than the minimum lethal dose for paraquat. The methodology presented here is used to assess the composition of complex matrices for the presence of contaminating molecules without a priori knowledge of the nature of potential contaminants. The ability to detect if a sample does not fit into the expected profile without recourse to multiple targeted analyses is a valuable tool for incident detection and forensic applications.

  8. 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.

  9. 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.

  10. 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.

  11. Investigating Festival's target cost function using perceptual experiments

    OpenAIRE

    Strom, Volker; King, Simon

    2008-01-01

    We describe an investigation of the target cost used in the Festival unit selection speech synthesis system. Our ultimate goal is to automatically learn a perceptually optimal target cost function. In this study, we investigated the behaviour of the target cost for one segment type. The target cost is based on counting the mismatches in several context features. A carrier sentence (``My name is Roger'') was synthesised using all 147,820 possible combinations of the diphones /n_ei/ and /ei_m/....

  12. 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

  13. Semantic priming in young and older adults: evidence for age constancy in automatic and attentional processes.

    Science.gov (United States)

    Burke, D M; White, H; Diaz, D L

    1987-02-01

    Automatic and attentional components of semantic priming and the relation of each to episodic memory were evaluated in young and older adults. Category names served as prime words, and the relatedness of the prime to a subsequent lexical decision target was varied orthogonally with whether the target category was expected or unexpected. At a prime-target stimulus-onset asynchrony (SOA) of 410 ms, target words in the same category had faster lexical decision latencies than did different category targets. This effect was not significant at a 1,550-ms SOA and was attributed to automatic processes. Expected category targets had faster latencies than unexpected category targets at the 410-ms SOA, and the magnitude of the effect increased at the 1,550-ms SOA. This effect was attributed to attentional processes. These patterns of priming were obtained for both age groups, but in a surprise memory test older adults had poorer recall of primes and targets. We discuss the implications of these results for the hypothesis that older adults suffer deficits in selective attention and for the related hypothesis that attentional deficits impair semantic processing, which causes memory decrements in old age.

  14. A Novel, Highly Selective Inhibitor of Pestivirus Replication That Targets the Viral RNA-Dependent RNA Polymerase

    Science.gov (United States)

    Paeshuyse, Jan; Leyssen, Pieter; Mabery, Eric; Boddeker, Nina; Vrancken, Robert; Froeyen, Matheus; Ansari, Israrul H.; Dutartre, Hélène; Rozenski, Jef; Gil, Laura H. V. G.; Letellier, Carine; Lanford, Robert; Canard, Bruno; Koenen, Frank; Kerkhofs, Pierre; Donis, Ruben O.; Herdewijn, Piet; Watson, Julia; De Clercq, Erik; Puerstinger, Gerhard; Neyts, Johan

    2006-01-01

    We report on the highly potent and selective antipestivirus activity of 5-[(4-bromophenyl)methyl]-2-phenyl-5H-imidazo[4,5-c]pyridine (BPIP). The 50% effective concentration (EC50) for inhibition of bovine viral diarrhea virus (BVDV)-induced cytopathic effect formation was 0.04 ± 0.01 μM. Comparable reduction of viral RNA synthesis (EC50 = 0.12 ± 0.02 μM) and production of infectious virus (EC50 = 0.074 ± 0.003 μM) were observed. The selectivity index (ratio of 50% cytostatic concentration/EC50) of BPIP was ∼2,000. BPIP was inactive against the hepatitis C virus subgenomic replicon and yellow fever virus but demonstrated weak activity against GB virus. Drug-resistant mutants were at least 300-fold less susceptible to BPIP than wild-type virus; showed cross-resistance to N-propyl-N-[2-(2H-1,2,4-triazino[5,6-b]indol-3-ylthio)ethyl]-1-propanamine (VP32947), and carried the F224S mutation in the viral RNA-dependent RNA polymerase (RdRp). When the F224S mutation was introduced into an infectious clone, the drug-resistant phenotype was obtained. BPIP did not inhibit the in vitro activity of recombinant BVDV RdRp, but did inhibit the activity of replication complexes (RCs). Computational docking revealed that F224 is located at the top of the finger domain of the polymerase. Docking of BPIP in the crystal structure of the BVDV RdRp revealed aromatic ring stacking, some hydrophobic contacts, and a hydrogen bond. Since two structurally unrelated compounds, i.e., BPIP and VP32947, target the same region of the BVDV RdRp, this position may be expected to be critical in the functioning of the polymerase or assembly of the RC. The potential of BPIP for the treatment of pestivirus and hepacivirus infections is discussed. PMID:16352539

  15. Dynamic Anthropometry – Deffning Protocols for Automatic Body Measurement

    Directory of Open Access Journals (Sweden)

    Slavenka Petrak

    2017-12-01

    Full Text Available The paper presents the research on possibilities of protocol development for automatic computer-based determination of measurements on a 3D body model in defined dynamic positions. Initially, two dynamic body positions were defined for the research on dimensional changes of targeted body lengths and surface segments during body movement from basic static position into a selected dynamic body position. The assumption was that during body movement, specifi c length and surface dimensions would change significantly from the aspect of clothing construction and functionality of a garment model. 3D body scanning of a female test sample was performed in basic static and two defined dynamic positions. 3D body models were processed and measurement points were defined as a starting point for the determination of characteristic body measurements. The protocol for automatic computer measurement was defined for every dynamic body position by the systematic set of activities based on determined measurement points. The verification of developed protocols was performed by automatic determination of defined measurements on the test sample and by comparing the results with the conventional manual measurement.

  16. Target Selection Recommendations Based on Impact of Deep Brain Stimulation Surgeries on Nonmotor Symptoms of Parkinson′s Disease

    Directory of Open Access Journals (Sweden)

    Xiao-Hong Wang

    2015-01-01

    Full Text Available 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 internus (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.

  17. Renal targeting of captopril selectively enhances the intrarenal over the systemic effects of ACE inhibition in rats

    Science.gov (United States)

    Haverdings, R Folgert G; Haas, Marijke; Navis, Gerjan; van Loenen-Weemaes, Anne-miek; Meijer, Dirk K F; de Zeeuw, Dick; Moolenaar, Frits

    2002-01-01

    In previous studies on the renal targeting of the ACE inhibitor captopril, we demonstrated that a 6 fold increased concentration of this drug could be obtained in the kidney after conjugation to the low-molecular-weight protein lysozyme. In this study, we investigated in unrestrained rats whether systemic administration of captopril–lysozyme also results in an enhanced effect on renal parameters, relative to the systemic effects. Renal effects: intravenous infusion of captopril–lysozyme for 6 h resulted in a more pronounced increment of renal blood flow (31±2% vs 17±4% at 0.5 mg kg−1 6h−1, Pcaptopril as a free drug. In correspondence with these findings, renal ACE inhibition was potentiated approximately 5 fold (−50±4% vs −22±3% at 1 mg kg−1 6 h−1, Pcaptopril did not affect blood pressure in dosages up to 5 mg kg−1 6 h−1. This effect coincided with a less pronounced inhibition of the pressor response to intravenously administered angiotensin I (−12±3% vs −66±5% at 1 mg kg−1 6 h−1, Pcaptopril. An experiment of continued intravenous administration of captopril–lysozyme for 7 days in nephrotic syndrome demonstrated that the conjugate is also active in renal disease: the antiproteinuric response was substantially augmented (−67±5% vs −15±7% at 4 mg kg−1 24 h−1, Pcaptopril–lysozyme conjugate leads to more selective renal ACE inhibition and enhanced renal effects as well as less systemic effects compared to captopril itself. PMID:12163343

  18. 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

  19. Automatic control systems engineering

    International Nuclear Information System (INIS)

    Shin, Yun Gi

    2004-01-01

    This book gives descriptions of automatic control for electrical electronics, which indicates history of automatic control, Laplace transform, block diagram and signal flow diagram, electrometer, linearization of system, space of situation, state space analysis of electric system, sensor, hydro controlling system, stability, time response of linear dynamic system, conception of root locus, procedure to draw root locus, frequency response, and design of control system.

  20. Neural Bases of Automaticity

    Science.gov (United States)

    Servant, Mathieu; Cassey, Peter; Woodman, Geoffrey F.; Logan, Gordon D.

    2018-01-01

    Automaticity allows us to perform tasks in a fast, efficient, and effortless manner after sufficient practice. Theories of automaticity propose that across practice processing transitions from being controlled by working memory to being controlled by long-term memory retrieval. Recent event-related potential (ERP) studies have sought to test this…

  1. Focusing Automatic Code Inspections

    NARCIS (Netherlands)

    Boogerd, C.J.

    2010-01-01

    Automatic Code Inspection tools help developers in early detection of defects in software. A well-known drawback of many automatic inspection approaches is that they yield too many warnings and require a clearer focus. In this thesis, we provide such focus by proposing two methods to prioritize

  2. Automatic differentiation of functions

    International Nuclear Information System (INIS)

    Douglas, S.R.

    1990-06-01

    Automatic differentiation is a method of computing derivatives of functions to any order in any number of variables. The functions must be expressible as combinations of elementary functions. When evaluated at specific numerical points, the derivatives have no truncation error and are automatically found. The method is illustrated by simple examples. Source code in FORTRAN is provided

  3. AUTOMATIC INTRAVENOUS DRIP CONTROLLER*

    African Journals Online (AJOL)

    Both the nursing staff shortage and the need for precise control in the administration of dangerous drugs intra- venously have led to the development of various devices to achieve an automatic system. The continuous automatic control of the drip rate eliminates errors due to any physical effect such as movement of the ...

  4. 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...

  5. 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

  6. Using an in Silico Approach to Teach 3D Pharmacodynamics of the Drug-Target Interaction Process Focusing on Selective COX2 Inhibition by Celecoxib

    Science.gov (United States)

    Tavares, Maurício T.; Primi, Marina C.; Silva, Nuno A. T. F.; Carvalho, Camila F.; Cunha, Micael R.; Parise-Filho, Roberto

    2017-01-01

    Teaching the molecular aspects of drug-target interactions and selectivity is not always an easy task. In this context, the use of alternative and engaging approaches could help pharmacy and chemistry students better understand this important topic of medicinal chemistry. Herein a 4 h practical exercise that uses freely available software as a…

  7. The Long-Term Effectiveness of a Selective, Personality-Targeted Prevention Program in Reducing Alcohol Use and Related Harms: A Cluster Randomized Controlled Trial

    Science.gov (United States)

    Newton, Nicola C.; Conrod, Patricia J.; Slade, Tim; Carragher, Natacha; Champion, Katrina E.; Barrett, Emma L.; Kelly, Erin V.; Nair, Natasha K.; Stapinski, Lexine; Teesson, Maree

    2016-01-01

    Background: This study investigated the long-term effectiveness of Preventure, a selective personality-targeted prevention program, in reducing the uptake of alcohol, harmful use of alcohol, and alcohol-related harms over a 3-year period. Methods: A cluster randomized controlled trial was conducted to assess the effectiveness of Preventure.…

  8. 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.

  9. Efficient Generation of Somatic Cell Nuclear Transfer-Competent Porcine Cells with Mutated Alleles at Multiple Target Loci by Using CRISPR/Cas9 Combined with Targeted Toxin-Based Selection System

    Directory of Open Access Journals (Sweden)

    Masahiro Sato

    2017-12-01

    Full Text Available The recent advancement in genome editing such a CRISPR/Cas9 system has enabled isolation of cells with knocked multiple alleles through a one-step transfection. Somatic cell nuclear transfer (SCNT has been frequently employed as one of the efficient tools for the production of genetically modified (GM animals. To use GM cells as SCNT donor, efficient isolation of transfectants with mutations at multiple target loci is often required. The methods for the isolation of such GM cells largely rely on the use of drug selection-based approach using selectable genes; however, it is often difficult to isolate cells with mutations at multiple target loci. In this study, we used a novel approach for the efficient isolation of porcine cells with at least two target loci mutations by one-step introduction of CRISPR/Cas9-related components. A single guide (sg RNA targeted to GGTA1 gene, involved in the synthesis of cell-surface α-Gal epitope (known as xenogenic antigen, is always a prerequisite. When the transfected cells were reacted with toxin-labeled BS-I-B4 isolectin for 2 h at 37 °C to eliminate α-Gal epitope-expressing cells, the surviving clones lacked α-Gal epitope expression and were highly expected to exhibit induced mutations at another target loci. Analysis of these α-Gal epitope-negative surviving cells demonstrated a 100% occurrence of genome editing at target loci. SCNT using these cells as donors resulted in the production of cloned blastocysts with the genotype similar to that of the donor cells used. Thus, this novel system will be useful for SCNT-mediated acquisition of GM cloned piglets, in which multiple target loci may be mutated.

  10. Target-specific NMR detection of protein–ligand interactions with antibody-relayed {sup 15}N-group selective STD

    Energy Technology Data Exchange (ETDEWEB)

    Hetényi, Anasztázia [University of Szeged, Department of Medical Chemistry (Hungary); Hegedűs, Zsófia [University of Szeged, SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis Department (Hungary); Fajka-Boja, Roberta; Monostori, Éva [Biological Research Center of the Hungarian Academy of Sciences, Lymphocyte Signal Transduction Laboratory, Institute of Genetics (Hungary); Kövér, Katalin E. [University of Debrecen, Department of Inorganic and Analytical Chemistry (Hungary); Martinek, Tamás A., E-mail: martinek@pharm.u-szeged.hu [University of Szeged, SZTE-MTA Lendület Foldamer Research Group, Institute of Pharmaceutical Analysis Department (Hungary)

    2016-12-15

    Fragment-based drug design has been successfully applied to challenging targets where the detection of the weak protein–ligand interactions is a key element. {sup 1}H saturation transfer difference (STD) NMR spectroscopy is a powerful technique for this work but it requires pure homogeneous proteins as targets. Monoclonal antibody (mAb)-relayed {sup 15}N-GS STD spectroscopy has been developed to resolve the problem of protein mixtures and impure proteins. A {sup 15}N-labelled target-specific mAb is selectively irradiated and the saturation is relayed through the target to the ligand. Tests on the anti-Gal-1 mAb/Gal-1/lactose system showed that the approach is experimentally feasible in a reasonable time frame. This method allows detection and identification of binding molecules directly from a protein mixture in a multicomponent system.

  11. 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.

  12. Automatic scanning of emulsion films

    International Nuclear Information System (INIS)

    D'Ambrosio, N.; Mandrioli, G.; Sirrib, G.

    2003-01-01

    The use of nuclear emulsions in recent large neutrino experiments is mostly due to the significant results in the developments of this detection technique. In the emulsion films, trajectories of through-going particles are permanently recorded: thus, the emulsion target can be considered not only as a tracking but also as a storing device. If the data readout is performed by automatic scanning systems interfaced to an acquisition computer equipped with a fast frame grabber, nuclear emulsions can be used as very large target detector and quickly analyzed in particle physics experiments. Techniques for automatic scanning of nuclear emulsions have been developed in the early past. The effort was initiated by Niwa at Nagoya (Japan) in the late 70s. The first large-scale application was the CHORUS experiment; then emulsions have been used to search for T neutrinos in a high track density environment like DONUT. In order to measure with high accuracy and high speed, very strict constraints must be satisfied in terms of mechanical precisions, camera speed, image processing power. Recent improvements in this technique are briefly reported

  13. Automatic Test Systems Aquisition

    National Research Council Canada - National Science Library

    1994-01-01

    We are providing this final memorandum report for your information and use. This report discusses the efforts to achieve commonality in standards among the Military Departments as part of the DoD policy for automatic test systems (ATS...

  14. Dual targeting of topoisomerase IV and gyrase to reduce mutant selection: direct testing of the paradigm by using WCK-1734, a new fluoroquinolone, and ciprofloxacin.

    Science.gov (United States)

    Strahilevitz, Jacob; Hooper, David C

    2005-05-01

    Quinolones that act equally against DNA gyrase and topoisomerase IV are a desirable modality to decrease the selection of resistant strains. We first determined by genetic and biochemical studies in Staphylococcus aureus that the primary target enzyme of WCK-1734, a new quinolone, was DNA gyrase. A single mutation in gyrase, but not topoisomerase IV, caused a two- to fourfold increase in the MIC. Studies with purified topoisomerase IV and gyrase from S. aureus also showed that gyrase was more sensitive than topoisomerase IV to WCK-1734 (50% inhibitory concentration, 1.25 and 2.5 to 5.0 microg/ml, respectively; 50% stimulation of cleavage complex formation, 0.62 and 2.5 to 5.0 microg/ml, respectively). To test the effect of balanced activity of quinolones against the two target enzymes, we measured the frequency of selection of mutants with ciprofloxacin (which targets topoisomerase IV) and WCK-1734 alone and in combination. With the combination of ciprofloxacin and WCK-1734, each at its MIC, the ratio of frequency of mutants selected was significantly lower than that with each drug alone at two times their respective MICs. We further characterized resistant strains selected with the combination of ciprofloxacin and WCK-1734 and found evidence to suggest the existence of novel mutational mechanisms for low-level quinolone resistance. By use of a combination of differentially targeting quinolones, this study provides novel data in direct support of the paradigm for dual targeting of quinolone action and reduced development of resistance.

  15. Automatic requirements traceability

    OpenAIRE

    Andžiulytė, Justė

    2017-01-01

    This paper focuses on automatic requirements traceability and algorithms that automatically find recommendation links for requirements. The main objective of this paper is the evaluation of these algorithms and preparation of the method defining algorithms to be used in different cases. This paper presents and examines probabilistic, vector space and latent semantic indexing models of information retrieval and association rule mining using authors own implementations of these algorithms and o...

  16. Position automatic determination technology

    International Nuclear Information System (INIS)

    1985-10-01

    This book tells of method of position determination and characteristic, control method of position determination and point of design, point of sensor choice for position detector, position determination of digital control system, application of clutch break in high frequency position determination, automation technique of position determination, position determination by electromagnetic clutch and break, air cylinder, cam and solenoid, stop position control of automatic guide vehicle, stacker crane and automatic transfer control.

  17. Empirical Evidence of Target Leverage, Adjustment Costs and Adjustment Speed of Non-Financial Firms in Selected African Countries

    OpenAIRE

    Oyebola Fatima Etudaiye-Muhtar; Oyebola Fatima Etudaiye-Muhtar; Rubi Ahmad

    2015-01-01

    The issue of target leverage for corporate firms in developing countries has received little attention in extant literature, especially countries in Africa. Given the imperfection that exists in African financial markets that may limit firms access to external capital, this study investigates dynamic adjustment towards a target debt ratio. In addition, the study used a dynamic panel data estimation technique to determine adjustment costs and speed of adjustment in non-financial firms in selec...

  18. Automatic feature selection using FS-NEAT

    OpenAIRE

    Ethembabaoglu, A.; Whiteson, S.

    2008-01-01

    This article describes a series of experiments used to analyze the FS-NEAT method on a double pole-balancing domain. The FS-NEAT method is compared with regular NEAT to discern its strengths and weaknesses. Both FS-NEAT and regular NEAT find a policy, implemented in a neural network, to solve the pole-balancing task by use of genetic algorithms. FS-NEAT, contrary to regular NEAT, uses a different starting population. Whereas regular NEAT networks start out with links between all the inputs an...

  19. Automatic Scheme Selection for Toolkit Hex Meshing

    Energy Technology Data Exchange (ETDEWEB)

    TAUTGES,TIMOTHY J.; WHITE,DAVID R.

    1999-09-27

    Current hexahedral mesh generation techniques rely on a set of meshing tools, which when combined with geometry decomposition leads to an adequate mesh generation process. Of these tools, sweeping tends to be the workhorse algorithm, accounting for at least 50% of most meshing applications. Constraints which must be met for a volume to be sweepable are derived, and it is proven that these constraints are necessary but not sufficient conditions for sweepability. This paper also describes a new algorithm for detecting extruded or sweepable geometries. This algorithm, based on these constraints, uses topological and local geometric information, and is more robust than feature recognition-based algorithms. A method for computing sweep dependencies in volume assemblies is also given. The auto sweep detect and sweep grouping algorithms have been used to reduce interactive user time required to generate all-hexahedral meshes by filtering out non-sweepable volumes needing further decomposition and by allowing concurrent meshing of independent sweep groups. Parts of the auto sweep detect algorithm have also been used to identify independent sweep paths, for use in volume-based interval assignment.

  20. Automatic feature selection using FS-NEAT

    NARCIS (Netherlands)

    Ethembabaoglu, A.; Whiteson, S.

    2008-01-01

    This article describes a series of experiments used to analyze the FS-NEAT method on a double pole-balancing domain. The FS-NEAT method is compared with regular NEAT to discern its strengths and weaknesses. Both FS-NEAT and regular NEAT find a policy, implemented in a neural network, to solve the

  1. Limitations of Short Range Mexican Hat Connection for Driving Target Selection in a 2D Neural Field: Activity Suppression and Deviation from Input Stimuli.

    Directory of Open Access Journals (Sweden)

    Geoffrey eMégardon

    2015-10-01

    Full Text Available Dynamic Neural Field models (DNF often use a kernel of connection with short range excitation and long range inhibition. This organization has been suggested as a model for brain structures or for artificial systems involved in winner-take-all processes such as saliency localisation, perceptual decision or target/action selection. A good example of such a DNF is the superior colliculus (SC, a key structure for eye movements. Recent results suggest that the superficial layers of the SC (SCs exhibit relatively short range inhibition with a longer time constant than excitation. The aim of the present study was to further examine the properties of a DNF with such an inhibition pattern in the context of target selection. First we tested the effects of stimulus size and shape on when and where self-maintained clusters of firing neurons appeared, using three variants of the model. In each model variant, small stimuli led to rapid formation of a spiking cluster, a range of medium sizes led to the suppression of any activity on the network and hence to no target selection, while larger sizes led to delayed selection of multiple loci. Second, we tested the model with two stimuli separated by a varying distance. Again single, none, or multiple spiking clusters could occur, depending on distance and relative stimulus strength. For short distances, activity attracted towards the strongest stimulus, reminiscent of well-known behavioural data for saccadic eye movements, while for larger distances repulsion away from the second stimulus occurred. All these properties predicted by the model suggest that the SCs, or any other neural structure thought to implement a short range MH, is an imperfect winner-take-all system. Although those properties call for systematic testing, the discussion gathers neurophysiological and behavioural data suggesting that such properties are indeed present in target selection for saccadic eye movements.

  2. Limitations of short range Mexican hat connection for driving target selection in a 2D neural field: activity suppression and deviation from input stimuli.

    Science.gov (United States)

    Mégardon, Geoffrey; Tandonnet, Christophe; Sumner, Petroc; Guillaume, Alain

    2015-01-01

    Dynamic Neural Field models (DNF) often use a kernel of connection with short range excitation and long range inhibition. This organization has been suggested as a model for brain structures or for artificial systems involved in winner-take-all processes such as saliency localization, perceptual decision or target/action selection. A good example of such a DNF is the superior colliculus (SC), a key structure for eye movements. Recent results suggest that the superficial layers of the SC (SCs) exhibit relatively short range inhibition with a longer time constant than excitation. The aim of the present study was to further examine the properties of a DNF with such an inhibition pattern in the context of target selection. First we tested the effects of stimulus size and shape on when and where self-maintained clusters of firing neurons appeared, using three variants of the model. In each model variant, small stimuli led to rapid formation of a spiking cluster, a range of medium sizes led to the suppression of any activity on the network and hence to no target selection, while larger sizes led to delayed selection of multiple loci. Second, we tested the model with two stimuli separated by a varying distance. Again single, none, or multiple spiking clusters could occur, depending on distance and relative stimulus strength. For short distances, activity attracted toward the strongest stimulus, reminiscent of well-known behavioral data for saccadic eye movements, while for larger distances repulsion away from the second stimulus occurred. All these properties predicted by the model suggest that the SCs, or any other neural structure thought to implement a short range MH, is an imperfect winner-take-all system. Although, those properties call for systematic testing, the discussion gathers neurophysiological and behavioral data suggesting that such properties are indeed present in target selection for saccadic eye movements.

  3. Physio-biochemical parameters: a potential tool for target-selective treatment of haemonchosis in the small ruminants.

    Science.gov (United States)

    Das, Bhupamani; Kumar, Niranjan; Jadav, Mehul M; Solanki, Jayesh B; Rao, T K S

    2017-12-01

    This study aims to evaluate the conjunctiva colour-based FAMACHA score (FS) coupled with a body condition score (BCS), haemogram and stressor hormone level estimation, in identifying post-mortem (PM)/coproscopically proven individuals wanting therapy for economically important gastrointestinal (GI) helminths, Haemonchus contortus, in the small ruminants. The incidence of haemonchosis was significantly (p  0.05). The infected animals of FS 2, 3 and 4 measured 8.2 ± 0.0, 7.5 ± 0.23 and 6.7 ± 0.34 g/dl Hb (r = -0.452, p = 0.01) in goats/9.3 ± 0.8, 8.6 ± 0.5 and 7.6 ± 0.3 g/dl Hb (r = -0.511, p = 0.05) in sheep with 21.2, 19.8 ± 1.8 and 17.8 ± 0.2% PCV (r = -0.369, p = 0.05) in goats/26.7 ± 1.2, 22.2 ± 0.2 and 20.9 ± 0.6% PCV (r = -0.251, p = 0.03) in sheep, respectively. The FS 2, 3 and 4 infected goats/sheep measured 6.1 ± 0, 7.9 ± 1.0 and 9.5 ± 0.9 (p < 0.05)/5.8 ± 2.3, 6.9 ± 1.2 and 7.8 ± 0.2% (p < 0.05) mid-granulocyte [(r = 0.928 (goats)/0.834 (sheep), p < 0.05], while the cortisol level was 15.6, 23 ± 4.5 and 42 ± 2.3 (p = 0.23)/12.1 ± 0, 15.9 ± 1.2 and 24 ± 3.4 (p = 0.29) μg/dl, respectively. The infected ruminants recorded low (p < 0.05) level of Hb/PCV while high level of mid-granulocytes/cortisol. Specificity of FAMACHA test was maximized (100%) when FS = 4 was considered anaemic, but sensitivity was low (35.29% in goats; 25% in sheep). The false negatives was 5.9 (goat)/12.5 (sheep)% when FS ≥ 3 was considered anaemic. The small ruminants with FS ≥ 3, BCS ≤ 2.5, Hb ≤ 7.5 g/dl (goats)/8.6 g/dl (sheep), PCV ≤ 19.8% (goats)/22.2% (sheep) and mid-granulocyte ≥7.9% (goats)/6.9 ± 1.2% (sheep) can be subjected to target-selective treatment for haemonchosis in the field simultaneously maximizing the economic benefit to the farmers.

  4. 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.

  5. Beam Energy Deposition from PS Booster and Production Rates of Selected Medical Radioisotopes in the CERN-MEDICIS Target

    OpenAIRE

    Gonsalves, Basil; Barlow, Roger; Dos Santos Augusto, Ricardo Manuel; Lee, Sangcheol; Stora, Thierry

    2016-01-01

    CERN-MEDICIS uses the scattered (ca. 90%) 1.4 GeV, 2 uA protons delivered by the PS Booster to the ISOLDE target, which would normally end up in the beam dump. After irradiation, the MEDICIS target is transported back to an offline isotope mass separator, where the produced isotopes are mass separated, and are then collected. The required medical radioisotopes are later chemically separated in the class A laboratory. The radioisotopes are transported to partner hospitals for processing and pr...

  6. Application of virtual screening and molecular dynamics for the analysis of selectivity of inhibitors of HU proteins targeted to the DNA-recognition site

    Science.gov (United States)

    Talyzina, A. A.; Agapova, Yu. K.; Podshivalov, D. D.; Timofeev, V. I.; Sidorov-Biryukov, D. D.; Rakitina, T. V.

    2017-11-01

    DNA-Binding HU proteins are essential for the maintenance of genomic DNA supercoiling and compaction in prokaryotic cells and are promising pharmacological targets for the design of new antibacterial agents. The virtual screening for low-molecular-weight compounds capable of specifically interacting with the DNA-recognition loop of the HU protein from the mycoplasma Spiroplasma melliferum was performed. The ability of the initially selected ligands to form stable complexes with the protein target was assessed by molecular dynamics simulation. One compound, which forms an unstable complex, was eliminated by means of a combination of computational methods, resulting in a decrease in the number of compounds that will pass to the experimental test phase. This approach can be used to solve a wide range of problems related to the search for and validation of low-molecular-weight inhibitors specific for a particular protein target.

  7. K-Targeted Metabolomic Analysis Extends Chemical Subtraction to DESIGNER Extracts: Selective Depletion of Extracts of Hops (Humulus lupulus)⊥

    Science.gov (United States)

    2015-01-01

    This study introduces a flexible and compound targeted approach to Deplete and Enrich Select Ingredients to Generate Normalized Extract Resources, generating DESIGNER extracts, by means of chemical subtraction or augmentation of metabolites. Targeting metabolites based on their liquid–liquid partition coefficients (K values), K targeting uses countercurrent separation methodology to remove single or multiple compounds from a chemically complex mixture, according to the following equation: DESIGNER extract = total extract ± target compound(s). Expanding the scope of the recently reported depletion of extracts by immunoaffinity or solid phase liquid chromatography, the present approach allows a more flexible, single- or multi-targeted removal of constituents from complex extracts such as botanicals. Chemical subtraction enables both chemical and biological characterization, including detection of synergism/antagonism by both the subtracted targets and the remaining metabolite mixture, as well as definition of the residual complexity of all fractions. The feasibility of the DESIGNER concept is shown by K-targeted subtraction of four bioactive prenylated phenols, isoxanthohumol (1), 8-prenylnaringenin (2), 6-prenylnaringenin (3), and xanthohumol (4), from a standardized hops (Humulus lupulus L.) extract using specific solvent systems. Conversely, adding K-targeted isolates allows enrichment of the original extract and hence provides an augmented DESIGNER material. Multiple countercurrent separation steps were used to purify each of the four compounds, and four DESIGNER extracts with varying depletions were prepared. The DESIGNER approach innovates the characterization of chemically complex extracts through integration of enabling technologies such as countercurrent separation, K-by-bioactivity, the residual complexity concepts, as well as quantitative analysis by 1H NMR, LC-MS, and HiFSA-based NMR fingerprinting. PMID:25437744

  8. 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.

  9. Tumor targeting efficiency of bare nanoparticles does not mean the efficacy of loaded anticancer drugs: importance of radionuclide imaging for optimization of highly selective tumor targeting polymeric nanoparticles with or without drug.

    Science.gov (United States)

    Lee, Beom Suk; Park, Kyeongsoon; Park, Sangjin; Kim, Gui Chul; Kim, Hyo Jung; Lee, Sangjoo; Kil, Heeseup; Oh, Seung Jun; Chi, Daeyoon; Kim, Kwangmeyung; Choi, Kuiwon; Kwon, Ick Chan; Kim, Sang Yoon

    2010-10-15

    The better understanding of polymeric nanoparticles as a drug delivery carrier is a decisive factor to get more efficient therapeutic response in vivo. Here, we report the non-invasive imaging of bare polymeric nanoparticles and drug-loaded polymeric nanoparticles to evaluate biodistribution in tumor bearing mice. To make nano-sized drug delivery carrier, glycol chitosan was modified with different degrees of hydrophobic N-acetyl histidine (NAcHis-GC-1, -2, and -3). The biodistribution of polymeric nanoparticles and drug was confirmed by using gamma camera with (131)I-labeled NAcHis-GC and (131)I-labeled doxorubicin (DOX) and by using in vivo live animal imaging with near-infrared fluorescence Cy5.5-labeled NAcHis-GC. Among bare nanoparticles, NAcHis-GC3 (7.8% NAcHis content) showed much higher tumor targeting efficiency than NAcHis-GC1 (3.3% NAcHis content) and NAcHis-GC2 (6.8% NAcHis content). In contrast, for drug-loaded nanoparticles, DOX-NAcHis-GC1 displayed two-fold higher tumor targeting property than DOX-NAcHis-GC3. These data imply that the biodistribution and tumor targeting efficiency between bare and drug-loaded nanoparticles may be greatly different. Therapeutic responses for NAcHis-GC nanoparticles after drug loading were also evaluated. In xenograft animal model, we could find out that DOX-NAcHis-GC1 with higher tumor targeting of DOX has more excellent therapeutic effect than DOX-NAcHis-GC3 and free DOX. These results mean that the hydrophobic core stability might be a critical factor for tumor targeting efficiency of nanoparticles. The present study indicates that by using molecular imaging, we can select more appropriate nanoparticles with the highest tumor targeting properties, leading to exerting more excellent therapeutic results in cancer therapy. Copyright © 2010 Elsevier B.V. All rights reserved.

  10. Impact of Novel LDL-C Assessment on the Utility of Secondary Non-HDL-C and ApoB Targets in Selected Worldwide Dyslipidemia Guidelines.

    Science.gov (United States)

    Sathiyakumar, Vasanth; Park, Jihwan; Quispe, Renato; Elshazly, Mohamed B; Michos, Erin D; Banach, Maciej; Toth, Peter P; Whelton, Seamus P; Blumenthal, Roger S; Jones, Steven R; Martin, Seth S

    2018-03-05

    Background -Selected dyslipidemia guidelines recommend non-high-density lipoprotein-cholesterol (non-HDL-C) and apolipoprotein B (apoB) as secondary targets to the primary target of low-density lipoprotein-cholesterol (LDL-C). We examined, after considering two LDL-C estimates that differ in accuracy: (1) how frequently non-HDL-C guideline targets could change management; and (2) utility of apoB targets after meeting LDL-C and non-HDL-C targets. Methods -We analyzed 2,518 adults representative of the U.S. population from the 2011-2012 National Health and Nutrition Examination Survey and 126,092 patients from the Very Large Database of Lipids study with apoB. We identified all individuals as well as those with high-risk clinical features including coronary disease, diabetes, and metabolic syndrome who met very high- and high-risk guideline targets of LDL-CC F ) and a novel, more accurate method (LDL-C N ). Next, we examined those not meeting non-HDL-C (C and non-HDL-C targets (CC F C≥100 mg/dL, and 7-8% had apoB≥80 mg/dL. Among those with LDL-C F C≥130 mg/dL and 2-3% had apoB≥100 mg/dL. In comparison, among those with LDL-C N C and apoB values above guideline targets. Similar trends were upheld among those with high-risk clinical features: ~0-3% of individuals with LDL-C N C≥100 mg/dL or apoB≥80 mg/dL compared to 13-38% and 9-25%, respectively, in those with LDL-C F C F or LDL-C N CC F or LDL-C N CC, guideline-suggested non-HDL-C targets could alter management in only a small fraction of individuals, including those with coronary disease and other high-risk clinical features. Furthermore, current guideline-suggested apoB targets provide modest utility after meeting cholesterol targets. Clinical Trial Registration -URL: https://clinicaltrials.gov Unique Identifier: NCT01698489.

  11. Application of a body condition score index for targeted selective treatment in adult Merino sheep--A modelling study.

    Science.gov (United States)

    Cornelius, M P; Jacobson, C; Besier, R B

    2015-11-30

    This study aimed to establish whether sheep flock production losses due to nematode (worm) infections are typically greater in mature sheep selected for anthelmintic treatment at random compared to sheep selected for treatment based on low (poorer) body condition score (BCS). The study also examined the proportion of sheep in flocks that could be left untreated before production losses became evident, and projected worm egg pasture contamination. Sheep were monitored at two experimental sites in Western Australia (Mediterranean climate). Sheep were stratified for BCS, liveweight and faecal worm egg count (WEC) and allocated into treatment groups (treated or untreated), with equal numbers for each. Liveweight, BCS and WEC measurements were taken on 6 occasions at Farm A and 10 occasions at Farm B. Comparisons of sheep production (liveweight and BCS change) and pasture contamination potential (WEC) were conducted by generating "virtual flocks" of varying proportions sheep untreated (10%, 20%, 30%, 40%, and 50% untreated). For the comparison of the selection mode of sheep for treatment, the untreated sheep were either selected at random, or as the highest BCS animals at the commencement of observations. Univariate general linear models with least square difference post-hoc tests were used to examine differences between flocks for liveweight, BCS and WEC, and regression analysis was used to examine relationships between BCS and WEC, and liveweight and WEC. No difference in body weights was observed between flocks with varying proportions of ewes notionally left untreated at Farm B, and until more than 30% were left untreated at Farm A. There was no difference in BCS between flocks with varying proportions of ewes left untreated at either site. At no point were there differences in cumulative liveweight change or BCS between selection methods (BCS versus random) where the same proportion of sheep in virtual flocks were left untreated, suggesting that effort committed to

  12. Automatic text summarization

    CERN Document Server

    Torres Moreno, Juan Manuel

    2014-01-01

    This new textbook examines the motivations and the different algorithms for automatic document summarization (ADS). We performed a recent state of the art. The book shows the main problems of ADS, difficulties and the solutions provided by the community. It presents recent advances in ADS, as well as current applications and trends. The approaches are statistical, linguistic and symbolic. Several exemples are included in order to clarify the theoretical concepts.  The books currently available in the area of Automatic Document Summarization are not recent. Powerful algorithms have been develop

  13. Automatic Ultrasound Scanning

    DEFF Research Database (Denmark)

    Moshavegh, Ramin

    on the scanners, and to improve the computer-aided diagnosis (CAD) in ultrasound by introducing new quantitative measures. Thus, four major issues concerning automation of the medical ultrasound are addressed in this PhD project. They touch upon gain adjustments in ultrasound, automatic synthetic aperture image...... on the user adjustments on the scanner interface to optimize the scan settings. This explains the huge interest in the subject of this PhD project entitled “AUTOMATIC ULTRASOUND SCANNING”. The key goals of the project have been to develop automated techniques to minimize the unnecessary settings...

  14. Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.

    Science.gov (United States)

    Lai, Hsiao-Lei; Wang, Q Tian

    2013-01-01

    Polycomb Group (PcG) proteins are epigenetic repressors of gene expression. The Drosophila Additional sex combs (Asx) gene and its mammalian homologs exhibit PcG function in genetic assays; however, the mechanism by which Asx family proteins mediate gene repression is not well understood. ASXL2, one of three mammalian homologs for Asx, is highly expressed in the mammalian heart and is required for the maintenance of cardiac function. We have previously shown that Asxl2 deficiency results in a reduction in the bulk level of histone H3 lysine 27 trimethylation (H3K27me3), a repressive mark generated by the Polycomb Repressive Complex 2 (PRC2). Here we identify several ASXL2 target genes in the heart and investigate the mechanism by which ASXL2 facilitates their repression. We show that the Asxl2-deficient heart is defective in converting H3K27me2 to H3K27me3 and in removing ubiquitin from mono-ubiquitinated histone H2A. ASXL2 and PRC2 interact in the adult heart and co-localize to target promoters. ASXL2 is required for the binding of PRC2 and for the enrichment of H3K27me3 at target promoters. These results add a new perspective to our understanding of the mechanisms that regulate PcG activity and gene repression.

  15. Additional sex combs-like 2 is required for polycomb repressive complex 2 binding at select targets.

    Directory of Open Access Journals (Sweden)

    Hsiao-Lei Lai

    Full Text Available Polycomb Group (PcG proteins are epigenetic repressors of gene expression. The Drosophila Additional sex combs (Asx gene and its mammalian homologs exhibit PcG function in genetic assays; however, the mechanism by which Asx family proteins mediate gene repression is not well understood. ASXL2, one of three mammalian homologs for Asx, is highly expressed in the mammalian heart and is required for the maintenance of cardiac function. We have previously shown that Asxl2 deficiency results in a reduction in the bulk level of histone H3 lysine 27 trimethylation (H3K27me3, a repressive mark generated by the Polycomb Repressive Complex 2 (PRC2. Here we identify several ASXL2 target genes in the heart and investigate the mechanism by which ASXL2 facilitates their repression. We show that the Asxl2-deficient heart is defective in converting H3K27me2 to H3K27me3 and in removing ubiquitin from mono-ubiquitinated histone H2A. ASXL2 and PRC2 interact in the adult heart and co-localize to target promoters. ASXL2 is required for the binding of PRC2 and for the enrichment of H3K27me3 at target promoters. These results add a new perspective to our understanding of the mechanisms that regulate PcG activity and gene repression.

  16. 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. Copyright © 2011 Elsevier B.V. All rights reserved.

  17. The role of natural selection in shaping genetic variation in a promising Chagas disease drug target: Trypanosoma cruzi trans-sialidase.

    Science.gov (United States)

    Gallant, Joseph P; Lima-Cordón, Raquel Asunción; Justi, Silvia A; Monroy, Maria Carlota; Viola, Toni; Stevens, Lori

    2018-04-21

    Rational drug design creates innovative therapeutics based on knowledge of the biological target to provide more effective and responsible therapeutics. Chagas disease, endemic throughout Latin America, is caused by Trypanosoma cruzi, a protozoan parasite. Current therapeutics are problematic with widespread calls for new approaches. Researchers are using rational drug design for Chagas disease and one target receiving considerable attention is the T. cruzi trans-sialidase protein (TcTS). In T. cruzi, trans-sialidase catalyzes the transfer of sialic acid from a mammalian host to coat the parasite surface membrane and avoid immuno-detection. However, the role of TcTS in pathology variance among and within genetic variants of the parasite is not well understood despite numerous studies. Previous studies reported the crystalline structure of TcTS and the TS protein structure in other trypanosomes where the enzyme is often inactive. However, no study has examined the role of natural selection in genetic variation in TcTS. To understand the role of natural selection in TcTS DNA sequence and protein variation, we examined a 471 bp portion of the TcTS gene from 48 T. cruzi samples isolated from insect vectors. Because there may be multiple parasite genotypes infecting one insect and there are multiple copies of TcTS per parasite genome, all 48 sequences had multiple polymorphic bases. To resolve these polymorphisms, we examined cloned sequences from two insect vectors. The data are analyzed to understand the role of natural selection in shaping genetic variation in TcTS and interpreted in light of the possible role of TcTS as a drug target. The analysis highlights negative or purifying selection on three amino acids previously shown to be important in TcTS transfer activity. One amino acid in particular, Tyr342, is a strong candidate for a drug target because it is under negative selection and amino acid substitutions inactivate TcTS transfer activity. Chagas disease

  18. A DVH-guided IMRT optimization algorithm for automatic treatment planning and adaptive radiotherapy replanning

    International Nuclear Information System (INIS)

    Zarepisheh, Masoud; Li, Nan; Long, Troy; Romeijn, H. Edwin; Tian, Zhen; Jia, Xun; Jiang, Steve B.

    2014-01-01

    Purpose: To develop a novel algorithm that incorporates prior treatment knowledge into intensity modulated radiation therapy optimization to facilitate automatic treatment planning and adaptive radiotherapy (ART) replanning. Methods: The algorithm automatically creates a treatment plan guided by the DVH curves of a reference plan that contains information on the clinician-approved dose-volume trade-offs among different targets/organs and among different portions of a DVH curve for an organ. In ART, the reference plan is the initial plan for the same patient, while for automatic treatment planning the reference plan is selected from a library of clinically approved and delivered plans of previously treated patients with similar medical conditions and geometry. The proposed algorithm employs a voxel-based optimization model and navigates the large voxel-based Pareto surface. The voxel weights are iteratively adjusted to approach a plan that is similar to the reference plan in terms of the DVHs. If the reference plan is feasible but not Pareto optimal, the algorithm generates a Pareto optimal plan with the DVHs better than the reference ones. If the reference plan is too restricting for the new geometry, the algorithm generates a Pareto plan with DVHs close to the reference ones. In both cases, the new plans have similar DVH trade-offs as the reference plans. Results: The algorithm was tested using three patient cases and found to be able to automatically adjust the voxel-weighting factors in order to generate a Pareto plan with similar DVH trade-offs as the reference plan. The algorithm has also been implemented on a GPU for high efficiency. Conclusions: A novel prior-knowledge-based optimization algorithm has been developed that automatically adjust the voxel weights and generate a clinical optimal plan at high efficiency. It is found that the new algorithm can significantly improve the plan quality and planning efficiency in ART replanning and automatic treatment

  19. 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...

  20. Selecting targets for the diagnosis of Schistosoma mansoni infection: An integrative approach using multi-omic and immunoinformatics data.

    Directory of Open Access Journals (Sweden)

    Gardenia B F Carvalho

    Full Text Available In order to effectively control and monitor schistosomiasis, new diagnostic methods are essential. Taking advantage of computational approaches provided by immunoinformatics and considering the availability of Schistosoma mansoni predicted proteome information, candidate antigens of schistosomiasis were selected and used in immunodiagnosis tests based on Enzime-linked Immunosorbent Assay (ELISA. The computational selection strategy was based on signal peptide prediction; low similarity to human proteins; B- and T-cell epitope prediction; location and expression in different parasite life stages within definitive host. Results of the above-mentioned analysis were parsed to extract meaningful biological information and loaded into a relational database developed to integrate them. In the end, seven proteins were selected and one B-cell linear epitope from each one of them was selected using B-cell epitope score and the presence of intrinsically disordered regions (IDRs. These predicted epitopes generated synthetic peptides that were used in ELISA assays to validate the rational strategy of in silico selection. ELISA was performed using sera from residents of areas of low endemicity for S. mansoni infection and also from healthy donors (HD, not living in an endemic area for schistosomiasis. Discrimination of negative (NEG and positive (INF individuals from endemic areas was performed using parasitological and molecular methods. All infected individuals were treated with praziquantel, and serum samples were obtained from them 30 and 180 days post-treatment (30DPT and 180DPT. Results revealed higher IgG levels in INF group than in HD and NEG groups when peptides 1, 3, 4, 5 and 7 were used. Moreover, using peptide 5, ELISA achieved the best performance, since it could discriminate between individuals living in an endemic area that were actively infected from those that were not (NEG, 30DPT, 180DPT groups. Our experimental results also indicate that

  1. Automatic coding method of the ACR Code

    International Nuclear Information System (INIS)

    Park, Kwi Ae; Ihm, Jong Sool; Ahn, Woo Hyun; Baik, Seung Kook; Choi, Han Yong; Kim, Bong Gi

    1993-01-01

    The authors developed a computer program for automatic coding of ACR(American College of Radiology) code. The automatic coding of the ACR code is essential for computerization of the data in the department of radiology. This program was written in foxbase language and has been used for automatic coding of diagnosis in the Department of Radiology, Wallace Memorial Baptist since May 1992. The ACR dictionary files consisted of 11 files, one for the organ code and the others for the pathology code. The organ code was obtained by typing organ name or code number itself among the upper and lower level codes of the selected one that were simultaneous displayed on the screen. According to the first number of the selected organ code, the corresponding pathology code file was chosen automatically. By the similar fashion of organ code selection, the proper pathologic dode was obtained. An example of obtained ACR code is '131.3661'. This procedure was reproducible regardless of the number of fields of data. Because this program was written in 'User's Defined Function' from, decoding of the stored ACR code was achieved by this same program and incorporation of this program into program in to another data processing was possible. This program had merits of simple operation, accurate and detail coding, and easy adjustment for another program. Therefore, this program can be used for automation of routine work in the department of radiology

  2. Automatic creation of simulation configuration

    International Nuclear Information System (INIS)

    Oudot, G.; Poizat, F.

    1993-01-01

    SIPA, which stands for 'Simulator for Post Accident', includes: 1) a sophisticated software oriented workshop SWORD (which stands for 'Software Workshop Oriented towards Research and Development') designed in the ADA language including integrated CAD system and software tools for automatic generation of simulation software and man-machine interface in order to operate run-time simulation; 2) a 'simulator structure' based on hardware equipment and software for supervision and communications; 3) simulation configuration generated by SWORD, operated under the control of the 'simulator structure' and run on a target computer. SWORD has already been used to generate two simulation configurations (French 900 MW and 1300 MW nuclear power plants), which are now fully operational on the SIPA training simulator. (Z.S.) 1 ref

  3. 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.

  4. Automatic inference of indexing rules for MEDLINE.

    Science.gov (United States)

    Névéol, Aurélie; Shooshan, Sonya E; Claveau, Vincent

    2008-11-19

    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. 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. 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. We expect the sets of ILP rules obtained in this experiment to be integrated into MTI.

  5. Asteroseismology of OB stars with hundreds of single snapshot spectra (and a few time-series of selected targets)

    Science.gov (United States)

    Simón-Díaz, S.

    2015-01-01

    Imagine we could do asteroseismology of large samples of OB-type stars by using just one spectrum per target. That would be great! But this is probably a crazy and stupid idea. Or maybe not. Maybe we have the possibility to open a new window to investigate stellar oscillations in massive stars that has been in front of us for many years, but has not attracted very much our attention: the characterization and understanding of the so-called macroturbulent broadening in OB-type stars.

  6. Metallogenic geologic prerequisites of sandstone-type uranium deposits and target area selection. Taking Erlian and Ordos basins as examples

    International Nuclear Information System (INIS)

    Chen Fazheng

    2002-01-01

    Sandstone-type uranium deposit is the main target of recent uranium prospecting and exploration. According to the metallogenic characteristics, sandstone-type uranium deposits are divided into three groups: paleo-channel type, interlayer oxidation zone type and phreatic interlayer oxidation type. The author makes an analysis on the geologic prerequisites of the three types of uranium deposits, the similarities and difference, and preliminarily summarizes genetic models of different types of uranium deposits. Finally, taking Erlian and Ordos basins as examples, the author makes an evaluation and a strategic analysis on the uranium metallogenic prospect of the above two basins

  7. Reactor component automatic grapple

    International Nuclear Information System (INIS)

    Greenaway, P.R.

    1982-01-01

    A grapple for handling nuclear reactor components in a medium such as liquid sodium which, upon proper seating and alignment of the grapple with the component as sensed by a mechanical logic integral to the grapple, automatically seizes the component. The mechanical logic system also precludes seizure in the absence of proper seating and alignment. (author)

  8. Automatic Commercial Permit Sets

    Energy Technology Data Exchange (ETDEWEB)

    Grana, Paul [Folsom Labs, Inc., San Francisco, CA (United States)

    2017-12-21

    Final report for Folsom Labs’ Solar Permit Generator project, which has successfully completed, resulting in the development and commercialization of a software toolkit within the cloud-based HelioScope software environment that enables solar engineers to automatically generate and manage draft documents for permit submission.

  9. Automatic Complexity Analysis

    DEFF Research Database (Denmark)

    Rosendahl, Mads

    1989-01-01

    One way to analyse programs is to to derive expressions for their computational behaviour. A time bound function (or worst-case complexity) gives an upper bound for the computation time as a function of the size of input. We describe a system to derive such time bounds automatically using abstrac...

  10. Cell penetrating synthetic antimicrobial peptides (SAMPs) exhibiting potent and selective killing of mycobacterium by targeting its DNA.

    Science.gov (United States)

    Sharma, Aashish; Pohane, Amol Arunrao; Bansal, Sandhya; Bajaj, Avinash; Jain, Vikas; Srivastava, Aasheesh

    2015-02-23

    Naturally occurring antimicrobial peptides (AMPs) are powerful defence tools to tackle pathogenic microbes. However, limited natural production and high synthetic costs in addition to poor selectivity limit large-scale use of AMPs in clinical settings. Here, we present a series of synthetic AMPs (SAMPs) that exhibit highly selective and potent killing of Mycobacterium (minimum inhibitory concentration <20 μg mL(-1)) over E. coli or mammalian cells. These SAMPs are active against rapidly multiplying as well as growth saturated Mycobacterium cultures. These SAMPs are not membrane-lytic in nature, and are readily internalized by Mycobacterium and mammalian cells; whereas in E. coli, the lipopolysaccharide layer inhibits their cellular uptake, and hence, their antibacterial action. Upon internalization, these SAMPs interact with the unprotected genomic DNA of mycobacteria, and impede DNA-dependent processes, leading to bacterial cell death. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

    Meslin, Camille; Monestier, Olivier; Di Pasquale, Elisa; Pascal, Géraldine; Persani, Luca; Fabre, Stéphane

    2013-01-01

    Bone Morphogenetic Protein 15 (BMP15) is a TGFβ-like oocyte-derived growth factor involved in ovarian folliculogenesis as a critical regulator of many granulosa cell processes. Alterations of the BMP15 gene have been found associated with different ovarian phenotypic effects depending on the species, from sterility to increased prolificacy in sheep, slight subfertility in mouse or associated with primary ovarian insufficiency (POI) in women. To investigate the evolving role of BMP15, a phylogenetic analysis of this particular TGFβ family member was performed. A maximum likelihood phylogenetic tree of several TGFβ/BMP family members expressed by the ovary showed that BMP15 has a very strong divergence and a rapid evolution compared to others. Moreover, among 24 mammalian species, we detected signals of positive selection in the hominidae clade corresponding to F146, L189 and Y235 residues in human BMP15. The biological importance of these residues was tested functionally after site directed-mutagenesis in a COV434 cells luciferase assay. By replacing the positively selected amino acid either by alanine or the most represented residue in other studied species, only L189A, Y235A and Y235C mutants showed a significant increase of BMP15 signaling when compared to wild type. Additionally, the Y235C mutant was more potent than wild type in inhibiting progesterone secretion of ovine granulosa cells in primary culture. Interestingly, the Y235C mutation was previously identified in association with POI in women. In conclusion, this study evidences that the BMP15 gene has evolved faster than other members of the TGFß family and was submitted to a positive selection pressure in the hominidae clade. Some residues under positive selection are of great importance for the normal function of the protein and thus for female fertility. Y235 represents a critical residue in the determination of BMP15 biological activity, thus indirectly confirming its role in the onset of POI in

  12. Small and Dim Target Detection via Lateral Inhibition Filtering and Artificial Bee Colony Based Selective Visual Attention

    Science.gov (United States)

    Duan, Haibin; Deng, Yimin; Wang, Xiaohua; Xu, Chunfang

    2013-01-01

    This paper proposed a novel bionic selective visual attention mechanism to quickly select regions that contain salient objects to reduce calculations. Firstly, lateral inhibition filtering, inspired by the limulus’ ommateum, is applied to filter low-frequency noises. After the filtering operation, we use Artificial Bee Colony (ABC) algorithm based selective visual attention mechanism to obtain the interested object to carry through the following recognition operation. In order to eliminate the camera motion influence, this paper adopted ABC algorithm, a new optimization method inspired by swarm intelligence, to calculate the motion salience map to integrate with conventional visual attention. To prove the feasibility and effectiveness of our method, several experiments were conducted. First the filtering results of lateral inhibition filter were shown to illustrate its noise reducing effect, then we applied the ABC algorithm to obtain the motion features of the image sequence. The ABC algorithm is proved to be more robust and effective through the comparison between ABC algorithm and popular Particle Swarm Optimization (PSO) algorithm. Except for the above results, we also compared the classic visual attention mechanism and our ABC algorithm based visual attention mechanism, and the experimental results of which further verified the effectiveness of our method. PMID:23991033

  13. A Parallel Sensing Technique for Automatic Bilayer Lipid Membrane Arrays Monitoring

    Directory of Open Access Journals (Sweden)

    Michele ROSSI

    2012-03-01

    Full Text Available Ion channels are transmembrane proteins responsible of cell signaling and a large part of pharmaceutical compounds are interacting with them. In-vitro testing of ion channels is a promising technique for high throughput screening (HTS in drug discovery and personalized medicine. Automated tests of single ion channels embedded in artificial bilayer lipid membranes (BLM is gaining attention over patch clamp technique due to its characteristic of performing parallel tests on selected sets of channels or multiple pharmaceutical targets. However, BLM arrays formation is a critical process based on manual and time-consuming techniques. In this paper, an automatic liquid dispensing system for BLM formation monitored in real-time by using low-noise current amplifiers is presented. As proof of this approach, concurrent formation of BLMs is shown. Additionally, single ion channel recordings on an automatically formed BLM is presented and discussed.

  14. Mitochondrially targeted ZFNs for selective degradation of pathogenic mitochondrial genomes bearing large-scale deletions or point mutations

    Science.gov (United States)

    Gammage, Payam A; Rorbach, Joanna; Vincent, Anna I; Rebar, Edward J; Minczuk, Michal

    2014-01-01

    We designed and engineered mitochondrially targeted obligate heterodimeric zinc finger nucleases (mtZFNs) for site-specific elimination of pathogenic human mitochondrial DNA (mtDNA). We used mtZFNs to target and cleave mtDNA harbouring the m.8993T>G point mutation associated with neuropathy, ataxia, retinitis pigmentosa (NARP) and the “common deletion” (CD), a 4977-bp repeat-flanked deletion associated with adult-onset chronic progressive external ophthalmoplegia and, less frequently, Kearns-Sayre and Pearson's marrow pancreas syndromes. Expression of mtZFNs led to a reduction in mutant mtDNA haplotype load, and subsequent repopulation of wild-type mtDNA restored mitochondrial respiratory function in a CD cybrid cell model. This study constitutes proof-of-principle that, through heteroplasmy manipulation, delivery of site-specific nuclease activity to mitochondria can alleviate a severe biochemical phenotype in primary mitochondrial disease arising from deleted mtDNA species. PMID:24567072

  15. High-resolution profiling of NMD targets in yeast reveals translational fidelity as a basis for substrate selection.

    Science.gov (United States)

    Celik, Alper; Baker, Richard; He, Feng; Jacobson, Allan

    2017-05-01

    Nonsense-mediated mRNA decay (NMD) plays an important role in eukaryotic gene expression, yet the scope and the defining features of NMD-targeted transcripts remain elusive. To address these issues, we reevaluated the genome-wide expression of annotated transcripts in yeast cells harboring deletions of the UPF1 , UPF2 , or UPF3 genes. Our new RNA-seq analyses confirm previous results of microarray studies, but also uncover hundreds of new NMD-regulated transcripts that had escaped previous detection, including many intron-containing pre-mRNAs and several noncoding RNAs. The vast majority of NMD-regulated transcripts are normal-looking protein-coding mRNAs. Our bioinformatics analyses reveal that this set of NMD-regulated transcripts generally have lower translational efficiency and higher ratios of out-of-frame translation. NMD-regulated transcripts also have lower average codon optimality scores and higher transition probability to nonoptimal codons. Collectively, our results generate a comprehensive catalog of yeast NMD substrates and yield new insights into the mechanisms by which these transcripts are targeted by NMD. © 2017 Celik et al.; Published by Cold Spring Harbor Laboratory Press for the RNA Society.

  16. Toward a mechanistic understanding of vulnerability to hook-and-line fishing: Boldness as the basic target of angling-induced selection.

    Science.gov (United States)

    Klefoth, Thomas; Skov, Christian; Kuparinen, Anna; Arlinghaus, Robert

    2017-12-01

    In passively operated fishing gear, boldness-related behaviors should fundamentally affect the vulnerability of individual fish and thus be under fisheries selection. To test this hypothesis, we used juvenile common-garden reared carp ( Cyprinus carpio ) within a narrow size range to investigate the mechanistic basis of behavioral selection caused by angling. We focused on one key personality trait (i.e., boldness), measured in groups within ponds, two morphological traits (body shape and head shape), and one life-history trait (juvenile growth capacity) and studied mean standardized selection gradients caused by angling. Carp behavior was highly repeatable within ponds. In the short term, over seven days of fishing, total length, not boldness, was the main predictor of angling vulnerability. However, after 20 days of fishing, boldness turned out to be the main trait under selection, followed by juvenile growth rate, while morphological traits were only weakly related to angling vulnerability. In addition, we found juvenile growth rate to be moderately correlated with boldness. Hence, direct selection on boldness will also induce indirect selection on juvenile growth and vice versa, but given that the two traits are not perfectly correlated, independent evolution of both traits is also possible. Our study is among the first to mechanistically reveal that energy-acquisition-related behaviors, and not growth rate per se, are key factors determining the probability of capture, and hence, behavioral traits appear to be the prime targets of angling selection. We predict an evolutionary response toward increased shyness in intensively angling-exploited fish stocks, possibly causing the emergence of a timidity syndrome.

  17. An automatic taxonomy of galaxy morphology using unsupervised machine learning

    Science.gov (United States)

    Hocking, Alex; Geach, James E.; Sun, Yi; Davey, Neil

    2018-01-01

    We present an unsupervised machine learning technique that automatically segments and labels galaxies in astronomical imaging surveys using only pixel data. Distinct from previous unsupervised machine learning approaches used in astronomy we use no pre-selection or pre-filtering of target galaxy type to identify galaxies that are similar. We demonstrate the technique on the Hubble Space Telescope (HST) Frontier Fields. By training the algorithm using galaxies from one field (Abell 2744) and applying the result to another (MACS 0416.1-2403), we show how the algorithm can cleanly separate early and late type galaxies without any form of pre-directed training for what an 'early' or 'late' type galaxy is. We then apply the technique to the HST Cosmic Assembly Near-infrared Deep Extragalactic Legacy Survey (CANDELS) fields, creating a catalogue of approximately 60 000 classifications. We show how the automatic classification groups galaxies of similar morphological (and photometric) type and make the classifications public via a catalogue, a visual catalogue and galaxy similarity search. We compare the CANDELS machine-based classifications to human-classifications from the Galaxy Zoo: CANDELS project. Although there is not a direct mapping between Galaxy Zoo and our hierarchical labelling, we demonstrate a good level of concordance between human and machine classifications. Finally, we show how the technique can be used to identify rarer objects and present lensed galaxy candidates from the CANDELS imaging.

  18. Testing of Auxotrophic Selection Markers for Use in the Moss Physcomitrella Provides New Insights into the Mechanisms of Targeted Recombination

    Directory of Open Access Journals (Sweden)

    Mikael Ulfstedt