WorldWideScience

Sample records for ground target identification

  1. Convolutional Models for Landmine Identification with Ground Penetrating Radar

    NARCIS (Netherlands)

    Roth, F.

    2005-01-01

    This thesis presents new developments in the area of target identification with ground penetrating radar (GPR) intended for the identification of plastic and metal cased antipersonnel (AP) landmines from a single measured GPR return signal, called A-scan. The target identification is formulated as a

  2. Finding the Enemy: Using 3-D Laser Radar (LADAR) Imaging for Real Time Combat Identification of Ground Targets in an Obscured Environment

    Science.gov (United States)

    2010-04-01

    Algorithms”, p. 197. 23 Ibid, p. 197. 24 http://encyclopedia2.thefreedictionary.com/Bayesian+theory, p. 1. 25 Abdallah, Mahmoud A., Tayib I. Samu , and...Bibliography Abdallah, Mahmoud A., Tayib I. Samu , and William A. Grissom. “Automatic Target Identification Using Neural Networks.” SPIE Vol

  3. Ground-based observations of the beta Cephei CoRoT main target HD 180642: abundance analysis and mode identification

    CERN Document Server

    Briquet, M; Morel, T; Aerts, C; De Cat, P; Mathias, P; Lefever, K; Miglio, A; Poretti, E; Martin-Ruiz, S; Paparo, M; Rainer, M; Carrier, F; Gutiérrez-Soto, J; Valtier, J C; Benko, J M; Bognár, Z; Niemczura, E; Amado, P J; Suárez, J C; Moya, A; Rodriguez-Lopez, C; Garrido, R

    2009-01-01

    The known beta Cephei star HD 180642 was observed by the CoRoT satellite in 2007. From the very high-precision light curve, its pulsation frequency spectrum could be derived for the first time (Degroote and collaborators). In this paper, we obtain additional constraints for forthcoming asteroseismic modeling of the target. Our results are based on both extensive ground-based multicolour photometry and high-resolution spectroscopy. We determine T_eff = 24 500+-1000 K and log g = 3.45+-0.15 dex from spectroscopy. The derived chemical abundances are consistent with those for B stars in the solar neighbourhood, except for a mild nitrogen excess. A metallicity Z = 0.0099+-0.0016 is obtained. Three modes are detected in photometry. The degree l is unambiguously identified for two of them: l = 0 and l = 3 for the frequencies 5.48694 1/d and 0.30818 1/d, respectively. The radial mode is non-linear and highly dominant with an amplitude in the U-filter about 15 times larger than the strongest of the other modes. For th...

  4. Nondestructive Testing and Target Identification

    Science.gov (United States)

    2016-12-21

    AFRL-AFOSR-VA-TR-2016-0371 Nondestructive Testing and Target Identification David Colton UNIVERSITY OF DELAWARE Final Report 12/20/2016 DISTRIBUTION...PROJECT NUMBER 5e.  TASK NUMBER 5f.  WORK UNIT NUMBER 7.  PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) UNIVERSITY OF DELAWARE 220 HULLIHEN HALL NEWARK...8/98) Prescribed by ANSI Std . Z39.18 Page 1 of 1FORM SF 298 12/21/2016https://livelink.ebs.afrl.af.mil/livelink/llisapi.dll AFOSR Grant FA9550-13-1

  5. Section 10: Ground Water - Waste Characteristics & Targets

    Science.gov (United States)

    HRS Training. The waste characteristics factor category in the ground water pathway is made up of two components: the toxicity/mobility of the most hazardous substance associated with the site and the hazardous waste quantity at the site.

  6. Open Targets: a platform for therapeutic target identification and validation

    Science.gov (United States)

    Koscielny, Gautier; An, Peter; Carvalho-Silva, Denise; Cham, Jennifer A.; Fumis, Luca; Gasparyan, Rippa; Hasan, Samiul; Karamanis, Nikiforos; Maguire, Michael; Papa, Eliseo; Pierleoni, Andrea; Pignatelli, Miguel; Platt, Theo; Rowland, Francis; Wankar, Priyanka; Bento, A. Patrícia; Burdett, Tony; Fabregat, Antonio; Forbes, Simon; Gaulton, Anna; Gonzalez, Cristina Yenyxe; Hermjakob, Henning; Hersey, Anne; Jupe, Steven; Kafkas, Şenay; Keays, Maria; Leroy, Catherine; Lopez, Francisco-Javier; Magarinos, Maria Paula; Malone, James; McEntyre, Johanna; Munoz-Pomer Fuentes, Alfonso; O'Donovan, Claire; Papatheodorou, Irene; Parkinson, Helen; Palka, Barbara; Paschall, Justin; Petryszak, Robert; Pratanwanich, Naruemon; Sarntivijal, Sirarat; Saunders, Gary; Sidiropoulos, Konstantinos; Smith, Thomas; Sondka, Zbyslaw; Stegle, Oliver; Tang, Y. Amy; Turner, Edward; Vaughan, Brendan; Vrousgou, Olga; Watkins, Xavier; Martin, Maria-Jesus; Sanseau, Philippe; Vamathevan, Jessica; Birney, Ewan; Barrett, Jeffrey; Dunham, Ian

    2017-01-01

    We have designed and developed a data integration and visualization platform that provides evidence about the association of known and potential drug targets with diseases. The platform is designed to support identification and prioritization of biological targets for follow-up. Each drug target is linked to a disease using integrated genome-wide data from a broad range of data sources. The platform provides either a target-centric workflow to identify diseases that may be associated with a specific target, or a disease-centric workflow to identify targets that may be associated with a specific disease. Users can easily transition between these target- and disease-centric workflows. The Open Targets Validation Platform is accessible at https://www.targetvalidation.org. PMID:27899665

  7. Experimental identification of microRNA targets

    DEFF Research Database (Denmark)

    Ørom, Ulf Andersson; Lund, Anders H

    2009-01-01

    microRNAs are small RNAs that regulate protein synthesis post-transcriptionally. Animal microRNAs recognize their targets by incomplete base pairing to sequence motifs most often present in the 3' untranslated region of their target mRNAs. This partial complementarity vastly expands the repertoire...... of potential targets and constitutes a problem for computational target prediction. Although computational analyses have shed light on important aspects of microRNA target recognition, several questions remain regarding how microRNAs can recognize and regulate their targets. Forward experimental approaches...... allow for an unbiased study of microRNA target recognition and may unveil novel, rare or uncommon target binding patterns. In this review we focus on animal microRNAs and the experimental approaches that have been described for identification of their targets....

  8. Modeling and analysis of ground target radiation cross section

    Institute of Scientific and Technical Information of China (English)

    SHI Xiang; LOU GuoWei; LI XingGuo

    2008-01-01

    Based on the analysis of the passive millimeter wave (MMW) radiometer detection, the ground target radiation cross section is modeled as the new token for the target MMW radiant characteristics. Its ap-plication and actual testing are discussed and analyzed. The essence of passive MMW stealth is target radiation cross section reduction.

  9. Detection and identification of human targets in radar data

    Science.gov (United States)

    Gürbüz, Sevgi Z.; Melvin, William L.; Williams, Douglas B.

    2007-04-01

    Radar offers unique advantages over other sensors, such as visual or seismic sensors, for human target detection. Many situations, especially military applications, prevent the placement of video cameras or implantment seismic sensors in the area being observed, because of security or other threats. However, radar can operate far away from potential targets, and functions during daytime as well as nighttime, in virtually all weather conditions. In this paper, we examine the problem of human target detection and identification using single-channel, airborne, synthetic aperture radar (SAR). Human targets are differentiated from other detected slow-moving targets by analyzing the spectrogram of each potential target. Human spectrograms are unique, and can be used not just to identify targets as human, but also to determine features about the human target being observed, such as size, gender, action, and speed. A 12-point human model, together with kinematic equations of motion for each body part, is used to calculate the expected target return and spectrogram. A MATLAB simulation environment is developed including ground clutter, human and non-human targets for the testing of spectrogram-based detection and identification algorithms. Simulations show that spectrograms have some ability to detect and identify human targets in low noise. An example gender discrimination system correctly detected 83.97% of males and 91.11% of females. The problems and limitations of spectrogram-based methods in high clutter environments are discussed. The SNR loss inherent to spectrogram-based methods is quantified. An alternate detection and identification method that will be used as a basis for future work is proposed.

  10. Synchronous identification of friendly targets

    Science.gov (United States)

    Telle, John M.; Roger, Stutz A.

    1998-01-01

    A synchronous communication targeting system for use in battle. The present invention includes a transceiver having a stabilizing oscillator, a synchronous amplifier and an omnidirectional receiver, all in electrical communication with each other. A remotely located beacon is attached to a blackbody radiation source and has an amplitude modulator in electrical communication with a optical source. The beacon's amplitude modulator is set so that the optical source transmits radiation frequency at approximately the same or lower amplitude than that of the blackbody radiation source to which the beacon is attached. The receiver from the transceiver is adapted to receive frequencies approximately at or below blackbody radiation signals and sends such signals to the synchronous amplifier. The synchronous amplifier then rectifies and amplifies those signals which correspond to the predetermined frequency to therefore identify whether the blackbody radiation source is friendly or not.

  11. MOONLIGHT I. IDENTIFICATION OF STATIONARY HUMAN TARGETS

    Science.gov (United States)

    subjects. The first experiment was conducted under no-moon illumination and the second, using the same subjects, was conducted under full moon . The...2) Directly related to size of target being observed, (3) Directly related to height of the observer’s eyes above the ground under full - moon conditions

  12. Ground-based observations of Kepler asteroseismic targets

    DEFF Research Database (Denmark)

    Uyttterhoeven , K.; Karoff, Christoffer

    2010-01-01

    We present the ground-based activities within the different working groups of the Kepler Asteroseismic Science Consortium (KASC). The activities aim at the systematic characterization of the 5000+ KASC targets, and at the collection of ground-based follow-up time-series data of selected promising...

  13. Outdoor Synthetic Aperture Acoustic Ground Target Measurements

    Science.gov (United States)

    2010-04-19

    1341 (2003). [11] C. A. Dimarzio, T. Shi, F. J. Blonigen et al., “ Laser -Induced Acoustic Landmine Detection,” The Journal Of The Acoustical Society...High Frequency A/S Coupling For Ap Buried Landmine Detection Using Laser Doppler Vibrometers,” Proc. SPIE 5415(1), 35-41 (2004). [16] Bishop, S... Dolphin Echolocation Clicks For Target Discrimination,” The Journal Of The Acoustical Society Of America 124(1), 657-666 (2008). [20] Y. Nakamura

  14. Equivalence of the Symbol Grounding and Quantum System Identification Problems

    Directory of Open Access Journals (Sweden)

    Chris Fields

    2014-02-01

    Full Text Available The symbol grounding problem is the problem of specifying a semantics for the representations employed by a physical symbol system in a way that is neither circular nor regressive. The quantum system identification problem is the problem of relating observational outcomes to specific collections of physical degrees of freedom, i.e., to specific Hilbert spaces. It is shown that with reasonable physical assumptions these problems are equivalent. As the quantum system identification problem is demonstrably unsolvable by finite means, the symbol grounding problem is similarly unsolvable.

  15. Ground-target detection system for digital video database

    Science.gov (United States)

    Liang, Yiqing; Huang, Jeffrey R.; Wolf, Wayne H.; Liu, Bede

    1998-07-01

    As more and more visual information is available on video, information indexing and retrieval of digital video data is becoming important. A digital video database embedded with visual information processing using image analysis and image understanding techniques such as automated target detection, classification, and identification can provide query results of higher quality. We address in this paper a robust digital video database system within which a target detection module is implemented and applied onto the keyframe images extracted by our digital library system. The tasks and application scenarios under consideration involve indexing video with information about detection and verification of artificial objects that exist in video scenes. Based on the scenario that the video sequences are acquired by an onboard camera mounted on Predator unmanned aircraft, we demonstrate how an incoming video stream is structured into different levels -- video program level, scene level, shot level, and object level, based on the analysis of video contents using global imagery information. We then consider that the keyframe representation is most appropriate for video processing and it holds the property that can be used as the input for our detection module. As a result, video processing becomes feasible in terms of decreased computational resources spent and increased confidence in the (detection) decisions reached. The architecture we proposed can respond to the query of whether artificial structures and suspected combat vehicles are detected. The architecture for ground detection takes advantage of the image understanding paradigm and it involves different methods to locate and identify the artificial object rather than nature background such as tree, grass, and cloud. Edge detection, morphological transformation, line and parallel line detection using Hough transform applied on key frame images at video shot level are introduced in our detection module. This function can

  16. Camouflage, detection and identification of moving targets

    Science.gov (United States)

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

    2013-01-01

    Nearly all research on camouflage has investigated its effectiveness for concealing stationary objects. However, animals have to move, and patterns that only work when the subject is static will heavily constrain behaviour. We investigated the effects of different camouflages on the three stages of predation—detection, identification and capture—in a computer-based task with humans. An initial experiment tested seven camouflage strategies on static stimuli. In line with previous literature, background-matching and disruptive patterns were found to be most successful. Experiment 2 showed that if stimuli move, an isolated moving object on a stationary background cannot avoid detection or capture regardless of the type of camouflage. Experiment 3 used an identification task and showed that while camouflage is unable to slow detection or capture, camouflaged targets are harder to identify than uncamouflaged targets when similar background objects are present. The specific details of the camouflage patterns have little impact on this effect. If one has to move, camouflage cannot impede detection; but if one is surrounded by similar targets (e.g. other animals in a herd, or moving background distractors), then camouflage can slow identification. Despite previous assumptions, motion does not entirely ‘break’ camouflage. PMID:23486439

  17. Research on target accuracy for ground-based lidar

    Science.gov (United States)

    Zhu, Ling; Shi, Ruoming

    2009-05-01

    In ground based Lidar system, the targets are used in the process of registration, georeferencing for point cloud, and also can be used as check points. Generally, the accuracy of capturing the flat target center is influenced by scanning range and scanning angle. In this research, the experiments are designed to extract accuracy index of the target center with 0-90°scan angles and 100-195 meter scan ranges using a Leica HDS3000 laser scanner. The data of the experiments are listed in detail and the related results are analyzed.

  18. Image-based air target identification

    Science.gov (United States)

    Glais, Thierry; Ayoun, Andre

    1994-09-01

    This paper presents the main results obtained through a study on aircraft identification and attitude estimation conducted by Thomson TRT Defense for the French Ministry of Defense/Direction Generale de l'Armement/Direction des Constructions Aeronautiques. The purpose of this study was automatic assistance to aircraft identification. Indeed, modern fight airplanes are equipped with optronic systems capable of detecting and tracking enemy aircraft. In order to react quickly, the pilot must know at least the target type and possibly its identity. Recognition of the target type and attitude is obtained by matching the observed image with patterns belonging to a database. Two matching algorithms, which have been tested, are presented. The first one, based on the contour Fourier transform, needs the complete target silhouette extraction. The second one, belonging to the class of prediction and verification algorithms, compares the individual parts of the target to the database and is able to recognize the target, even when it is partially occluded or ill-segmented due to the lack of contrast between the target and its environment. An original feature of the algorithm stays in a validation process which increases the reliability of transmitted answers. In case of low confidence, no answer is provided. In addition, successive answers are consolidated. This strategy is interesting especially for image sequences where the tracked airplane achieves attitude evolution or even simply flies over various backgrounds. The main output of this study is the parametric analysis of various factors which influence performance such as contrast, background complexity, distance, attitude and type. The evaluation method, largely based on image synthesis (including image sequences), allows fine interpretation of statistical results. Misclassification errors occur when resolution is not sufficient or when complex backgrounds cause erroneous segmentation. Best results are obtained when the

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

    Science.gov (United States)

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

    2014-11-01

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

  20. Application of Road Information in Ground Moving Target Tracking

    Institute of Scientific and Technical Information of China (English)

    Zhen Xinyan; Zhao Wei

    2007-01-01

    A new algorithm is developed to achieve accurate state estimation in ground moving target tracking by means of using road information. It is an adaptive variable structure interacting multiple model estimator with dynamic models modification (DMM VS-IMM for short). Firstly, road information is employed to modify the target dynamic models used by filter, including modification of state transition matrix and process noise. Secondly, road information is applied to update the model set of a VS-IMM estimator. Predicted state estimation and road information are used to locate the target in the road network on which the model set is updated and finally IMM filtering is implemented. As compared with traditional methods, the accuracy of state estimation is improved for target moving not only on a single road, but also through an intersection. Monte Carlo simulation demonstrates the efficiency and robustness of the proposed algorithm with moderate computational loads.

  1. Nanorobot architecture for medical target identification

    Science.gov (United States)

    Cavalcanti, Adriano; Shirinzadeh, Bijan; Freitas, Robert A., Jr.; Hogg, Tad

    2008-01-01

    This work has an innovative approach for the development of nanorobots with sensors for medicine. The nanorobots operate in a virtual environment comparing random, thermal and chemical control techniques. The nanorobot architecture model has nanobioelectronics as the basis for manufacturing integrated system devices with embedded nanobiosensors and actuators, which facilitates its application for medical target identification and drug delivery. The nanorobot interaction with the described workspace shows how time actuation is improved based on sensor capabilities. Therefore, our work addresses the control and the architecture design for developing practical molecular machines. Advances in nanotechnology are enabling manufacturing nanosensors and actuators through nanobioelectronics and biologically inspired devices. Analysis of integrated system modeling is one important aspect for supporting nanotechnology in the fast development towards one of the most challenging new fields of science: molecular machines. The use of 3D simulation can provide interactive tools for addressing nanorobot choices on sensing, hardware architecture design, manufacturing approaches, and control methodology investigation.

  2. Nanorobot architecture for medical target identification

    Energy Technology Data Exchange (ETDEWEB)

    Cavalcanti, Adriano [CAN Center for Automation in Nanobiotech, Melbourne VIC 3168 (Australia); Shirinzadeh, Bijan [Robotics and Mechatronics Research Laboratory, Department of Mechanical Engineering, Monash University, Clayton, Melbourne VIC 3800 (Australia); Freita, Robert A Jr [Institute for Molecular Manufacturing, Pilot Hill, CA 95664 (United States); Hogg, Tad [Hewlett-Packard Laboratories, Palo Alto, CA 94304 (United States)

    2008-01-09

    This work has an innovative approach for the development of nanorobots with sensors for medicine. The nanorobots operate in a virtual environment comparing random, thermal and chemical control techniques. The nanorobot architecture model has nanobioelectronics as the basis for manufacturing integrated system devices with embedded nanobiosensors and actuators, which facilitates its application for medical target identification and drug delivery. The nanorobot interaction with the described workspace shows how time actuation is improved based on sensor capabilities. Therefore, our work addresses the control and the architecture design for developing practical molecular machines. Advances in nanotechnology are enabling manufacturing nanosensors and actuators through nanobioelectronics and biologically inspired devices. Analysis of integrated system modeling is one important aspect for supporting nanotechnology in the fast development towards one of the most challenging new fields of science: molecular machines. The use of 3D simulation can provide interactive tools for addressing nanorobot choices on sensing, hardware architecture design, manufacturing approaches, and control methodology investigation.

  3. BIOLOGICAL NANOROBOT ARCHITECTURE FOR MEDICAL TARGET IDENTIFICATION

    Directory of Open Access Journals (Sweden)

    S. Paul and Dipti*

    2012-07-01

    Full Text Available This work has an innovative approach for the development of biological nanorobots with sensors for medicine. The biological nanorobots operate in a virtual environment based on random, thermal and chemical control techniques. The biological nanorobot architecture model has biological nano bioelectronics as the basis for manufacturing integrated system devices with embedded biological nano biosensors and actuators, which facilitates its application for medical target identification and drug delivery. The biological nanorobot interaction with the described workspace shows how these biological nanorobots detect the target area and supply the drug. Therefore, our work addresses the control and the architecture design for developing practical molecular machines. Advances in nanotechnology are enabling manufacturing nanosensors and actuators through nano bioelectronics and biologically inspired devices. Analysis of integrated system modeling is one important aspect for supporting nanotechnology in the fast development towards one of the most challenging new fields of science: molecular machines. The use of 3D simulation can provide interactive tools for addressing nanorobot choices on sensing, hardware architecture design, manufacturing approaches, and control methodology investigation.

  4. THE METHOD of computation images matching with the standard AS A METHOD FOR IDENTIFICATION OF MOVING Ground OBJECTS

    Directory of Open Access Journals (Sweden)

    B. V. Kazbekov

    2014-01-01

    Full Text Available The article focuses on the identification of moving ground targets on board unmanned aerial vehicle. The possibility of realization of algorithm for identification of objects in real-time by comparing the image of the object under consideration and a set of reference images of the objects of the classes are considered. The merit of the developed modification and the results of the experiments are given.

  5. Ground-based observations of Kepler asteroseismic targets

    CERN Document Server

    Uytterhoeven, K; Southworth, J; Randall, S; Ostensen, R; Molenda-Zakowicz, J; Marconi, M; Kurtz, D W; Kiss, L; Gutierrez-Soto, J; Frandsen, S; De Cat, P; Bruntt, H; Briquet, M; Zhang, X B; Telting, J H; Steslicki, M; Ripepi, V; Pigulski, A; Paparo, M; Oreiro, R; Choong, Ngeow Chow; Niemczura, E; Nemec, J; Narwid, A; Mathias, P; Martin-Ruiz, S; Lehman, H; Kopacki, G; Karoff, C; Jackiewicz, J; Henden, A A; Handler, G; Grigachene, A; Green, E M; Garrido, R; Machado, L Fox; Debosscher, J; Creevey, O L; Catanzaro, G; Bognar, Z; Biazzo, K; Bernabei, S

    2010-01-01

    We present the ground-based activities within the different working groups of the Kepler Asteroseismic Science Consortium (KASC). The activities aim at the systematic characterization of the 5000+ KASC targets, and at the collection of ground-based follow-up time-series data of selected promising Kepler pulsators. So far, 35 different instruments at 30 telescopes on 22 different observatories in 12 countries are in use, and a total of more than 530 observing nights has been awarded. (Based on observations made with the Isaac Newton Telescope, William Herschel Telescope, Nordic Optical Telescope, Telescopio Nazionale Galileo, Mercator Telescope (La Palma, Spain), and IAC-80 (Tenerife, Spain). Also based on observations taken at the observatories of Sierra Nevada, San Pedro Martir, Vienna, Xinglong, Apache Point, Lulin, Tautenburg, Loiano, Serra la Nave, Asiago, McDonald, Skinakas, Pic du Midi, Mauna Kea, Steward Observatory, Bialkow Observatory of the Wroclaw University, Piszkesteto Mountain Station, Observato...

  6. Identification of SUMO target proteins by quantitative proteomics

    DEFF Research Database (Denmark)

    Andersen, Jens S; Matic, Ivan; Vertegaal, Alfred C O

    2009-01-01

    The identification of target proteins for small ubiquitin-like modifiers (SUMOs) is a critical step towards a detailed understanding of the cellular functions of SUMOs. Substrate protein identification for SUMOs is hampered by the low abundance of SUMO targets, the finding that only a small fract...

  7. Passive synthetic aperture radar imaging of ground moving targets

    Science.gov (United States)

    Wacks, Steven; Yazici, Birsen

    2012-05-01

    In this paper we present a method for imaging ground moving targets using passive synthetic aperture radar. A passive radar imaging system uses small, mobile receivers that do not radiate any energy. For these reasons, passive imaging systems result in signicant cost, manufacturing, and stealth advantages. The received signals are obtained by multiple airborne receivers collecting scattered waves due to illuminating sources of opportunity such as commercial television, radio, and cell phone towers. We describe a novel forward model and a corresponding ltered-backprojection type image reconstruction method combined with entropy optimization. Our method determines the location and velocity of multiple targets moving at dierent velocities. Furthermore, it can accommodate arbitrary imaging geometries. we present numerical simulations to verify the imaging method.

  8. Identification of rainy periods from ground based microwave radiometry

    Directory of Open Access Journals (Sweden)

    Ada Vittoria Bosisio

    2012-03-01

    Full Text Available In this paper the authors present the results of a study aiming at detecting rainy data in measurements collected by a dual band ground-based radiometer. The proposed criterion is based on the ratio of the brightness temperatures observed in the 20-30 GHz band without need of any ancillary information. A major result obtained from the probability density of the ratio computed over one month of data is the identification of threshold values between clear sky, cloudy sky and rainy sky, respectively. A linear fit performed by using radiometric data and concurrent rain gauge measurements shows a correlation coefficient equal to 0.56 between the temperature ratio and the observed precipitation.

  9. State estimators for tracking sharply-maneuvering ground targets

    Science.gov (United States)

    Visina, Radu S.; Bar-Shalom, Yaakov; Willett, Peter

    2017-05-01

    This paper presents an algorithm, based on the Interacting Multiple Model Estimator, that can be used to track the state of kinematic point targets, moving in two dimensions, that are capable of making sharp heading maneuvers over short periods of time, such as certain ground vehicles moving in an open field. The targets are capable of up to 60 °/s turn rates, while polar measurements are received at 1 Hz. We introduce the Non-Zero Mean, White Noise Turn-Rate IMM (IMM-WNTR) that consists of 3 modes based on a White Noise Turn Rate (WNTR) kinematic model that contains additive, white, Gaussian turn rate process noises. Two of the modes are considered maneuvering modes, and they have opposite (left/right), non-zero mean turn rate input noise. The need for non-zero mean turn rate process noise is explained, and Monte Carlo simulations compare this novel design to the traditional (single-mode) White Noise Acceleration Kalman Filter (WNA KF) and the two-mode White Noise Acceleration/Nearly-Coordinated Turn Rate IMM (IMM-CT). Results show that the IMM-WNTR filter achieves better accuracy and real-time consistency between expected error and actual error as compared to the (single-mode) WNA KF and the IMM-CT in all simulated scenarios, making it a very accurate state estimator for targets with sharp coordinated turn capability in 2D.

  10. System Identification and Automatic Mass Balancing of Ground-Based Three-Axis Spacecraft Simulator

    Science.gov (United States)

    2006-08-01

    System Identification and Automatic Mass Balancing of Ground-Based Three-Axis Spacecraft Simulator Jae-Jun Kim∗ and Brij N. Agrawal † Department of...TITLE AND SUBTITLE System Identification and Automatic Mass Balancing of Ground-Based Three-Axis Spacecraft Simulator 5a. CONTRACT NUMBER 5b...and Dynamics, Vol. 20, No. 4, July-August 1997, pp. 625-632. 6Schwartz, J. L. and Hall, C. D., “ System Identification of a Spherical Air-Bearing

  11. [Thalidomide teratogenicity and its direct target identification].

    Science.gov (United States)

    Ito, Takumi; Ando, Hideki; Handa, Hiroshi

    2015-01-01

    Half a century ago, thalidomide was developed as a sedative drug and was wildly used over 40 countries. However the drug has serious birth defects such as amelia and phocomelia. Now thalidomide is regarded as a clinically effective drug and used for the treatment of multiple myeloma under strict controls. The direct target of thalidomide had been a long-standing question. We identified cereblon as a primary direct target protein for thalidomide teratogenicity using new affinity bead technology in 2010. In this review, we introduce an overview of thalidomide teratogenicity, a story about how we identified cereblon, and recent advances in cereblon studies.

  12. Accurate Target Identification Using Multi-look Fusion of Low Quality Target Signatures

    Science.gov (United States)

    2008-12-01

    qualité, ce qui pourrait avoir des conséquences importantes pour les applications pratiques. D’une part, l’apparition de technologies de capteurs et...identification performance and this is not adequate for many target identification applications . Furthermore, in order for the single-look procedure to...obtenues qu’avec un un seul capteur . Toutefois, force est de constater que le rendement de l’identification correcte d’objectifs par l’approche

  13. Double-layered target and identification method of individual target correlated with evaporation residues

    Energy Technology Data Exchange (ETDEWEB)

    Kaji, D., E-mail: daiya@riken.jp; Morimoto, K.

    2015-08-21

    A double-layered target system and an identification method (target ID) for individual targets mounted on a rotating wheel using correlation with evaporation residues were newly developed for the study of superheavy elements (SHE). The target system can be used in three modes: conventional single-layered mode, double-layered mode, and energy-degrader mode. The target ID method can be utilized for masking a target, measuring an excitation function without changing the beam energy from the accelerator, and searching for SHE nuclides using multiple targets during a single irradiation.

  14. Progress in miRNA target prediction and identification

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    Recently, the identification of miRNA targets has received much attention. The strategies to determine miRNA targets include bioinformatic prediction and experimental assays. The bioinformatic prediction methods are mainly based on the confirmed rules of interaction between miRNAs and their targets, and are carried out by programs, such as miRanda, TargetScan, TargetScanS, RNAhybrid, DIANA-microT, PicTar, RNA22 and FindTar, which follow well-known principles. The experimental assays to find miRNA targets employ immunoprecipitation of AGO proteins to identify interacting mRNAs, or the analysis of mRNA or protein levels to identify genes which can be regulated by miRNAs. The improvement of current bioinformatic and experimental assays and the development of novel assays will enable greater efficiency in the identification of miRNA targets and thus facilitate miRNA research. This paper describes progress in the prediction and identification of miRNA targets.

  15. Electromagnetic modelling of Ground Penetrating Radar responses to complex targets

    Science.gov (United States)

    Pajewski, Lara; Giannopoulos, Antonis

    2014-05-01

    defined through a constant real value, or else its frequency-dispersion properties can be taken into account by incorporating into the model Debye approximations. The electromagnetic source can be represented as a simple line of current (in the case of two-dimensional models), a Hertzian dipole, a bow tie antenna, or else, the realistic description of a commercial antenna can be included in the model [2]. Preliminary results for some of the proposed cells are presented, obtained by using GprMax [3], a freeware tool which solves Maxwell's equations by using a second order in space and time Finite-Difference Time-Domain algorithm. B-Scans and A-Scans are calculated at 1.5 GHz, for the total electric field and for the field back-scattered by targets embedded in the cells. A detailed description of the structures, together with the relevant numerical results obtained to date, are available for the scientific community on the website of COST Action TU1208, www.GPRadar.eu. Research groups working on the development of electromagnetic forward- and inverse-scattering techniques, as well as on imaging methods, might test and compare the accuracy and applicability of their approaches on the proposed set of scenarios. The aim of this initiative is not that of identifying the best methods, but more properly to indicate the range of reliability of each approach, highlighting its advantages and drawbacks. In the future, the realisation of the proposed concrete cells and the acquisition of GPR experimental data would allow a very effective benchmark for forward and inverse scattering methods. References [1] R. Yelf, A. Ward, "Nine steps to concrete wisdom." Proc. 13th International Conference on Ground Penetrating Radar, Lecce, Italy, 21-25 June 2010, pp. 1-8. [2] C. Warren, A. Giannopoulos, "Creating FDTD models of commercial GPR antennas using Taguchi's optimisation method." Geophysics (2011), 76, article ID G37. [3] A. Giannopoulos, "Modelling ground penetrating radar by GPRMAX

  16. Strategies for target identification of antimicrobial natural products.

    Science.gov (United States)

    Farha, Maya A; Brown, Eric D

    2016-05-04

    Covering: 2000 to 2015Despite a pervasive decline in natural product research at many pharmaceutical companies over the last two decades, natural products have undeniably been a prolific and unsurpassed source for new lead antibacterial compounds. Due to their inherent complexity, natural extracts face several hurdles in high-throughout discovery programs, including target identification. Target identification and validation is a crucial process for advancing hits through the discovery pipeline, but has remained a major bottleneck. In the case of natural products, extremely low yields and limited compound supply further impede the process. Here, we review the wealth of target identification strategies that have been proposed and implemented for the characterization of novel antibacterials. Traditionally, these have included genomic and biochemical-based approaches, which, in recent years, have been improved with modern-day technology and better honed for natural product discovery. Further, we discuss the more recent innovative approaches for uncovering the target of new antibacterial natural products, which have resulted from modern advances in chemical biology tools. Finally, we present unique screening platforms implemented to streamline the process of target identification. The different innovative methods to respond to the challenge of characterizing the mode of action for antibacterial natural products have cumulatively built useful frameworks that may advocate a renovated interest in natural product drug discovery programs.

  17. Vibrating Ground Target Detection and Feature Extraction of One-stationary Bistatic Frequency-modulated Continuous-wave Synthetic Aperture Radar

    Directory of Open Access Journals (Sweden)

    Liang Ying

    2015-12-01

    Full Text Available One of the unique characteristics of a ground target is its micro-motion, which can be used for target classification and identification. In this study, methods for vibrating ground target detection and feature extraction of the one-stationary bistatic frequency-modulated continuous-wave Synthetic Aperture Radar (SAR are studied. The Displaced Phase Center Antenna (DPCA technique is adopted to suppress the ground clutter, allowing the ground-vibrating targets to be detected. Analysis of the received signal indicates that the DPCA processing results in a slow time-varying envelope, known as the Slow Time Envelope (STE. The STE has a direct effect on the micro-Doppler time-frequency curve, which therefore cannot be obtained unbroken. Furthermore, vibrating features are extracted by utilizing their relationship with the STE term. Finally, some simulations are provided to validate the theoretical derivation and effectiveness of the proposed extraction method.

  18. Identification of Littoral Targets with a Laser Range Profiler

    NARCIS (Netherlands)

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

    2007-01-01

    Naval operations in the littoral have to deal with threats at short range in cluttered environments with both neutral and hostile targets. On board naval vessels there is a need for fast identification, which is possible with a laser range profiler. Additionally, in a coast-surveillance scenario a

  19. Parameter Estimation of a Ground Moving Target Using Image Sharpness Optimization.

    Science.gov (United States)

    Yu, Jing; Li, Yaan

    2016-06-30

    Motion parameter estimation of a ground moving target is an important issue in synthetic aperture radar ground moving target indication (SAR-GMTI) which has significant applications for civilian and military. The SAR image of a moving target may be displaced and defocused due to the radial and along-track velocity components, respectively. The sharpness cost function presents a measure of the degree of focus of the image. In this work, a new ground moving target parameter estimation algorithm based on the sharpness optimization criterion is proposed. The relationships between the quadratic phase errors and the target's velocity components are derived. Using two-dimensional searching of the sharpness cost function, we can obtain the velocity components of the target and the focused target image simultaneously. The proposed moving target parameter estimation method and image sharpness metrics are analyzed in detail. Finally, numerical results illustrate the effective and superior velocity estimation performance of the proposed method when compared to existing algorithms.

  20. Novel identification strategy for ground coffee adulteration based on UPLC-HRMS oligosaccharide profiling.

    Science.gov (United States)

    Cai, Tie; Ting, Hu; Jin-Lan, Zhang

    2016-01-01

    Coffee is one of the most common and most valuable beverages. According to International Coffee Organization (ICO) reports, the adulteration of coffee for financial reasons is regarded as the most serious threat to the sustainable development of the coffee market. In this work, a novel strategy for adulteration identification in ground coffee was developed based on UPLC-HRMS oligosaccharide profiling. Along with integrated statistical analysis, 17 oligosaccharide composition were identified as markers for the identification of soybeans and rice in ground coffee. This strategy, validated by manual mixtures, optimized both the reliability and authority of adulteration identification. Rice and soybean adulterants present in ground coffee in amounts as low as 5% were identified and evaluated. Some commercial ground coffees were also successfully tested using this strategy.

  1. Identification of Naegleria fowleri in warm ground water aquifers.

    Science.gov (United States)

    Laseke, Ian; Korte, Jill; Lamendella, Regina; Kaneshiro, Edna S; Marciano-Cabral, Francine; Oerther, Daniel B

    2010-01-01

    The free-living amoeba Naegleria fowleri was identified as the etiological agent of primary amoebic meningoencephalitis that caused the deaths of two children in Peoria, Arizona, in autumn of 2002. It was suspected that the source of N. fowleri was the domestic water supply, which originates from ground water sources. In this study, ground water from the greater Phoenix Metropolitan area was tested for the presence of N. fowleri using a nested polymerase chain reaction approach. Phylogenetic analyses of 16S rRNA sequences of bacterial populations in the ground water were performed to examine the potential link between the presence of N. fowleri and bacterial groups inhabiting water wells. The results showed the presence of N. fowleri in five out of six wells sampled and in 26.6% of all ground water samples tested. Phylogenetic analyses showed that beta- and gamma-proteobacteria were the dominant bacterial populations present in the ground water. Bacterial community analyses revealed a very diverse community structure in ground water samples testing positive for N. fowleri.

  2. Identification of Potential Fishing Grounds Using Geospatial Technique

    Science.gov (United States)

    Abdullah, Muhammad

    2016-07-01

    Fishery resources surveys using actual sampling and data collection methods require extensive ship time and sampling time. Informative data from satellite plays a vital role in fisheries application. Satellite Remote Sensing techniques can be used to detect fish aggregation just like visual fish identification ultimately these techniques can be used to predict the potential fishing zones by measuring the parameters which affect the distribution of fishes. Remote sensing is a time saving technique to locate fishery resources along the coast. Pakistan has a continental shelf area of 50,270 km2 and coastline length of 1,120 km. The total maritime zone of Pakistan is over 30 percent of the land area. Fishery plays an important role in the national economy. The marine fisheries sector is the main component, contributing about 57 percent in terms of production. Fishery is the most important economic activity in the villages and towns along the coast, and in most of the coastal villages and settlements it is the sole source of employment and income generation. Fishing by fishermen is done on the sole basis of repeated experiments and collection of information from other fishermen. Often they are in doubt about the location of potential fishing zones. This leads to waste of time and money, adversely affecting fishermen incomes and over or under-exploitation of fishing zones. The main purpose of this study was to map potential fishing grounds by identifying various environmental parameters which impact fish aggregation along the Pakistan coastline. The primary reason of this study is the fact that the fishing communities of Pakistan's coastal regions are extremely poor and lack knowledge of the modern tools and techniques that may be incorporated to enhance their yield and thus, improve their livelihood. Using geospatial techniques in order to accurately map the potential fishing zones based on sea surface temperature (SST) and chlorophyll -a content, in conjunction with

  3. Ground Target Overflight and Orbital Maneuvering via Atmospheric Maneuvers

    Science.gov (United States)

    2014-03-27

    al., 2002:228-230). Prior to the commencement of any research into aeroassisted maneuvers, a firm foundation in the understanding of atmospheric...cosine term is used for prograde orbits while the negative term is used for retrograde orbits. The r(1), r(2), and r(3) terms rerpresent the 1st... retrograde ) only target longitude crossings which occur in the same hemisphere as the 44 target are possible to overfly without changing the inclination

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

    Science.gov (United States)

    Amadieu, Jean-Louis; Fraysse, Vincent

    1996-06-01

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

  5. Network output controllability-based method for drug target identification.

    Science.gov (United States)

    Wu, Lin; Shen, Yichao; Li, Min; Wu, Fang-Xiang

    2015-03-01

    Biomolecules do not perform their functions alone, but interactively with one another to form so called biomolecular networks. It is well known that a complex disease stems from the malfunctions of corresponding biomolecular networks. Therefore, one of important tasks is to identify drug targets from biomolecular networks. In this study, the drug target identification is formulated as a problem of finding steering nodes in biomolecular networks while the concept of network output controllability is applied to the problem of drug target identification. By applying control signals to these steering nodes, the biomolecular networks are expected to be transited from one state to another. A graph-theoretic algorithm has been proposed to find a minimum set of steering nodes in biomolecular networks which can be a potential set of drug targets. Application results of the method to real biomolecular networks show that identified potential drug targets are in agreement with existing research results. This indicates that the method can generate testable predictions and provide insights into experimental design of drug discovery.

  6. Artificial ground motion compatible with specified peak velocity and target spectrum

    Institute of Scientific and Technical Information of China (English)

    ZHAO Feng-xin; ZHANG Yu-shan

    2006-01-01

    In this paper, a method, which synthesizes the artificial ground motion compatible with the specified peak velocity as well as the target acceleration response spectrum, was proposed. In this method, firstly, an initial acceleration time history a(0)g (t), which satisfies the prescribed peak ground acceleration, the target spectral acceleration ST(ω,ζ ), and the specified intensity envelope, is generated by the traditional method that generates the response-spectrum-compatible artificial ground motion by modifying the Fourier amplitude spectrum in the frequency domain; secondly, a(0)g (t) is further modulated by superimposing narrow-band time histories upon it in the time domain to make its peak velocity, approach the target peak ground velocity, and at the same time to improve its fitting precision to the target spectrum. Numerical examples show that this algorithm boasts high calculation precisions.

  7. TF Target Mapper: a BLAST search tool for the identification of Transcription Factor target genes

    NARCIS (Netherlands)

    Horsman, S.; Moorhouse, M.J.; Jager, V.C.L. de; Spek, P. van der; Grosveld, F.; Strouboulis, J.; Katsantoni, E.Z.

    2006-01-01

    BACKGROUND: In the current era of high throughput genomics a major challenge is the genome-wide identification of target genes for specific transcription factors. Chromatin immunoprecipitation (ChIP) allows the isolation of in vivo binding sites of transcription factors and provides a powerful tool

  8. STARR: shortwave-targeted agile Raman robot for the detection and identification of emplaced explosives

    Science.gov (United States)

    Gomer, Nathaniel R.; Gardner, Charles W.

    2014-05-01

    In order to combat the threat of emplaced explosives (land mines, etc.), ChemImage Sensor Systems (CISS) has developed a multi-sensor, robot mounted sensor capable of identification and confirmation of potential threats. The system, known as STARR (Shortwave-infrared Targeted Agile Raman Robot), utilizes shortwave infrared spectroscopy for the identification of potential threats, combined with a visible short-range standoff Raman hyperspectral imaging (HSI) system for material confirmation. The entire system is mounted onto a Talon UGV (Unmanned Ground Vehicle), giving the sensor an increased area search rate and reducing the risk of injury to the operator. The Raman HSI system utilizes a fiber array spectral translator (FAST) for the acquisition of high quality Raman chemical images, allowing for increased sensitivity and improved specificity. An overview of the design and operation of the system will be presented, along with initial detection results of the fusion sensor.

  9. SCENARIO AND TARGET SIMULATION FOR A GROUND BASED MULTIFUNCTION PHASED ARRAY RADAR

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    This paper describes a scenario and target simulation which operates in non real-time to provide full closed-loop operation of the ground based multifunction phased array radar simulation system in support of ballistic missile defence experiments against countermeasure.By simulating the target scattering signature and dynamical signature,this scenario and target simulation provide re- alistic scenario source to evaluate the system performance of multifunction phased array radar,and the key algorithms verification and validation such as target tracking,multi-target imaging and target recognition.

  10. Genesis Concentrator Target Particle Contamination Mapping and Material Identification

    Science.gov (United States)

    Calaway, Michael J.; Rodriquez, M. C.; Allton, J. H.

    2007-01-01

    The majority of surface particles were found to be Genesis science team as well as ultra-pure water megasonic cleaning by the JSC team [4]. Removal of organic contamination from target materials is also being investigated by the science team with the use of UV-ozone cleaning devices at JSC and Open University [5]. In preparation for solar wind oxygen analyses at UCLA and Open University [1, 2], surface particle contamination on three Genesis concentrator targets was closely examined to evaluate cleaning strategies. Two silicon carbide (Genesis sample # 60001 and 60003) and one chemical vapor deposited (CVD) 13C concentrator target (60002) were imaged and mosaic mapped with optical microscopes. The resulting full target mosaic images and particle feature maps were subsequently compared with non-flight, but flight-like, concentrator targets and sample return capsule (SRC) materials. Contamination found on the flown concentrator acceleration grid was further examined using a scanning electron microscope (SEM). Energy dispersive X-ray spectroscopy (EDS) for particle identification was subsequently compared with the optical images from the flown targets. Figure 1 show that all three targets imaged in this report are fully intact and do not show any signs of material fractures. However, previous ellipsometry results and overview imaging of both flown SiC targets show a solar wind irradiation gradient from the center focal point to the outer edge [3]. In addition, due to the hard landing, each target has experienced varying degrees of impacts, scratches, and particle debris from the spacecraft and Utah impact site.

  11. Screening Technologies for Target Identification in Pancreatic Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Michl, Patrick, E-mail: michlp@med.uni-marburg.de; Ripka, Stefanie; Gress, Thomas; Buchholz, Malte [Department of Gastroenterology and Endocrinology, University Hospital, Philipps-University Marburg, Baldinger Strasse, D-35043 Marburg (Germany)

    2010-12-29

    Pancreatic cancer exhibits an extraordinarily high level of resistance to almost any kind of systemic therapy evaluated in clinical trials so far. Therefore, the identification of novel therapeutic targets is urgently required. High-throughput screens have emerged as an important tool to identify putative targets for diagnosis and therapy in an unbiased manner. More than a decade ago, microarray technology was introduced to identify differentially expressed genes in pancreatic cancer as compared to normal pancreas, chronic pancreatitis and other cancer types located in close proximity to the pancreas. In addition, proteomic screens have facilitated the identification of differentially secreted proteins in body fluids of pancreatic cancer patients, serving as possible biomarkers. Recently, RNA interference-based loss-of-function screens have been used to identify functionally relevant genes, whose knock-down has impact on pancreatic cancer cell viability, thereby representing potential new targets for therapeutic intervention. This review summarizes recent results of transcriptional, proteomic and functional screens in pancreatic cancer and discusses potentials and limitations of the respective technologies as well as their impact on future therapeutic developments.

  12. Identification of Fungal Colonies on Ground Control and Flight Veggie Plant Pillows

    Science.gov (United States)

    Scotten, Jessica E.; Hummerick, Mary E.; Khodadad, Christina L.; Spencer, Lashelle E.; Massa, Gioia D.

    2017-01-01

    The Veggie system focuses on growing fresh produce that can be harvested and consumed by astronauts. The microbial colonies in each Veggie experiment are evaluated to determine the safety level of the produce and then differences between flight and ground samples. The identifications of the microbial species can detail risks or benefits to astronaut and plant health. Each Veggie ground or flight experiment includes six plants grown from seeds that are glued into wicks in Teflon pillows filled with clay arcillite and fertilizer. Fungal colonies were isolated from seed wicks, growth media, and lettuce (cv. 'Outredgeous') roots grown in VEG-01B pillows on ISS and in corresponding ground control pillows grown in controlled growth chambers. The colonies were sorted by morphology and identified using MicroSeq(TM) 500 16s rDNA Bacterial Identification System and BIOLOG GEN III MicroPlate(TM). Health risks for each fungal identification were then assessed using literature sources. The goal was to identify all the colonies isolated from flight and ground control VEG-01B plants, roots, and rooting medium and compare the resulting identifications.

  13. Identification of cellular targets of a series of boron heterocycles using TIPA II-A sensitive target identification platform.

    Science.gov (United States)

    Ward, Matthew S; Silva, Isba; Martinez, Walfre; Jefferson, Jameka; Rahman, Shakila; Garcia, Jeanie M; Kanichar, Divya; Roppiyakuda, Lance; Kosmowska, Ewa; Faust, Michelle A; Tran, Kim P; Chow, Felicia; Buglo, Elena; Zhou, Feimeng; Groziak, Michael P; Xu, H Howard

    2016-08-01

    One of the hurdles in the discovery of antibiotics is the difficulty of linking antibacterial compounds to their cellular targets. Our laboratory has employed a genome-wide approach of over-expressing essential genes in order to identify cellular targets of antibacterial inhibitors. Our objective in this project was to develop and validate a more sensitive disk diffusion based platform of target identification (Target Identification Platform for Antibacterials version 2; TIPA II) using a collection of cell clones in an Escherichia coli mutant (AS19) host with increased outer membrane permeability. Five known antibiotics/inhibitors and 28 boron heterocycles were tested by TIPA II assay, in conjunction with the original assay TIPA. The TIPA II was more sensitive than TIPA because eight boron heterocycles previously found to be inactive to AG1 cells in TIPA assays exhibited activity to AS19 cells. For 15 boron heterocycles, resistant colonies were observed within the zones of inhibition only on the inducing plates in TIPA II assays. DNA sequencing confirmed that resistant clones harbor plasmids with fabI gene as insert, indicating that these boron heterocycles all target enoyl ACP reductase. Additionally, cell-based assays and dose response curved obtained indicated that for two boron heterocycle inhibitors, the fabI cell clone in AG1 (wild-type) host cells exhibited at least 11 fold more resistance under induced conditions than under non-induced conditions. Moreover, TIPA II also identified cellular targets of known antibacterial inhibitors triclosan, phosphomycin, trimethoprim, diazaborine and thiolactomycin, further validating the utility of the new system.

  14. Identification of novel Notch target genes in T cell leukaemia

    Directory of Open Access Journals (Sweden)

    Warrander Fiona

    2009-06-01

    Full Text Available Abstract Background Dysregulated Notch signalling is believed to play an important role in the development and maintenance of T cell leukaemia. At a cellular level, Notch signalling promotes proliferation and inhibits apoptosis of T cell acute lymphoblastic leukaemia (T-ALL cells. In this study we aimed to identify novel transcriptional targets of Notch signalling in the T-ALL cell line, Jurkat. Results RNA was prepared from Jurkat cells retrovirally transduced with an empty vector (GFP-alone or vectors containing constitutively active forms of Notch (N1ΔE or N3ΔE, and used for Affymetrix microarray analysis. A subset of genes found to be regulated by Notch was chosen for real-time PCR validation and in some cases, validation at the protein level, using several Notch-transduced T-ALL and non-T-ALL leukaemic cell lines. As expected, several known transcriptional target of Notch, such as HES1 and Deltex, were found to be overexpressed in Notch-transduced cells, however, many novel transcriptional targets of Notch signalling were identified using this approach. These included the T cell costimulatory molecule CD28, the anti-apoptotic protein GIMAP5, and inhibitor of DNA binding 1 (1D1. Conclusion The identification of such downstream Notch target genes provides insights into the mechanisms of Notch function in T cell leukaemia, and may help identify novel therapeutic targets in this disease.

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

    Directory of Open Access Journals (Sweden)

    Zheng Shi-chao

    2013-12-01

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

  16. miRNAs target databases: developmental methods and target identification techniques with functional annotations.

    Science.gov (United States)

    Singh, Nagendra Kumar

    2017-06-01

    the need of more intelligent computational improvement for the miRNA target identification, their functional annotations and datasbase development.

  17. IFPTarget: A Customized Virtual Target Identification Method Based on Protein-Ligand Interaction Fingerprinting Analyses.

    Science.gov (United States)

    Li, Guo-Bo; Yu, Zhu-Jun; Liu, Sha; Huang, Lu-Yi; Yang, Ling-Ling; Lohans, Christopher T; Yang, Sheng-Yong

    2017-07-24

    Small-molecule target identification is an important and challenging task for chemical biology and drug discovery. Structure-based virtual target identification has been widely used, which infers and prioritizes potential protein targets for the molecule of interest (MOI) principally via a scoring function. However, current "universal" scoring functions may not always accurately identify targets to which the MOI binds from the retrieved target database, in part due to a lack of consideration of the important binding features for an individual target. Here, we present IFPTarget, a customized virtual target identification method, which uses an interaction fingerprinting (IFP) method for target-specific interaction analyses and a comprehensive index (Cvalue) for target ranking. Evaluation results indicate that the IFP method enables substantially improved binding pose prediction, and Cvalue has an excellent performance in target ranking for the test set. When applied to screen against our established target library that contains 11,863 protein structures covering 2842 unique targets, IFPTarget could retrieve known targets within the top-ranked list and identified new potential targets for chemically diverse drugs. IFPTarget prediction led to the identification of the metallo-β-lactamase VIM-2 as a target for quercetin as validated by enzymatic inhibition assays. This study provides a new in silico target identification tool and will aid future efforts to develop new target-customized methods for target identification.

  18. RADAR HRR PROFILING FOR GROUND MOVING TARGET USING PHASE-CODED AND HOPPED-FREQUENCY WAVEFORMS

    Institute of Scientific and Technical Information of China (English)

    Li Yan; Wang Changming

    2007-01-01

    To obtain the radar High Range Resolution (HRR) profile of the slowly moving ground target in strong clutter background, the Phase-Coded Hopped-Frequency (PCHF) waveform is proposed. By multiple-bursts coherent processing, the HRR profile synthesis, target velocity compensation and clutter compression can be accomplished simultaneously. The new waveform is shown to have good ability to suppress ground clutter and good Electronic Counter-CounterMeasures (ECCM) ability as well. The clutter compression performance of the proposed method is verified by the numerical results.

  19. Identification of therapeutic targets in a model of neuropathic pain

    Directory of Open Access Journals (Sweden)

    Hemalatha B Raju

    2014-05-01

    Full Text Available Neuropathic pain (NP is caused by damage to the nervous system, resulting in dysfunction and aberrant pain. The cellular functions (e.g. peripheral neuron spinal cord innervation, neuronal excitability associated with NP often develop over time and are likely associated with gene expression changes. Gene expression studies on the cells involved in NP (e.g. sensory dorsal root ganglion neurons are publically available; the mining of these studies may enable the identification of novel targets and the subsequent development of therapies that are essential for improving quality of life for the millions of individuals suffering with NP. Here we analyzed a publically available microarray dataset (GSE30165 in order to identify new RNAs (e.g. messenger RNA isoforms and non-coding RNAs underlying NP. GSE30165 profiled gene expression in dorsal root ganglion neurons (DRG and in sciatic nerve (SN after resection, a NP model. Gene ontological analysis shows enrichment for sensory and neuronal processes. Protein network analysis demonstrates DRG upregulated genes typical to an injury and NP response. Of the top changing genes, 34% and 36% are associated with more than one protein coding isoform in the dorsal root ganglia (DRG and sciatic nerve (SN respectively. The majority of genes are receptor and enzymes. We identified fifteen long non-coding RNAs (lncRNAs targeting these genes in LNCipedia.org, an online comprehensive lncRNA database. These RNAs represent new therapeutic targets for preventing NP development and this approach demonstrates the feasibility of data reanalysis for their identification.

  20. Low velocity target detection based on time-frequency image for high frequency ground wave radar

    Institute of Scientific and Technical Information of China (English)

    YAN Songhua; WU Shicai; WEN Biyang

    2007-01-01

    The Doppler spectral broadening resulted from non-stationary movement of target and radio-frequency interference will decrease the veracity of target detection by high frequency ground wave(HEGW)radar.By displaying the change of signal energy on two dimensional time-frequency images based on time-frequency analysis,a new mathematical morphology method to distinguish target from nonlinear time-frequency curves is presented.The analyzed results from the measured data verify that with this new method the target can be detected correctly from wide Doppler spectrum.

  1. Parameter Estimation of a Ground Moving Target Using Image Sharpness Optimization

    Directory of Open Access Journals (Sweden)

    Jing Yu

    2016-06-01

    Full Text Available Motion parameter estimation of a ground moving target is an important issue in synthetic aperture radar ground moving target indication (SAR-GMTI which has significant applications for civilian and military. The SAR image of a moving target may be displaced and defocused due to the radial and along-track velocity components, respectively. The sharpness cost function presents a measure of the degree of focus of the image. In this work, a new ground moving target parameter estimation algorithm based on the sharpness optimization criterion is proposed. The relationships between the quadratic phase errors and the target’s velocity components are derived. Using two-dimensional searching of the sharpness cost function, we can obtain the velocity components of the target and the focused target image simultaneously. The proposed moving target parameter estimation method and image sharpness metrics are analyzed in detail. Finally, numerical results illustrate the effective and superior velocity estimation performance of the proposed method when compared to existing algorithms.

  2. Ground moving target signal model and power calculation in forward scattering micro radar

    Institute of Scientific and Technical Information of China (English)

    LONG Teng; HU Cheng; MIKHAIL Cherniakov

    2009-01-01

    Forward scattering micro radar is used for situation awareness;its operational range is relatively short because of the battery power and local horizon,the free space propagation model is not appropriate.The ground moving targets,such as humans,cars and tanks,have only comparable size with the transmitted signal wavelength;the point target model and the linear change of observation angle are not applicable.In this paper,the signal model of ground moving target is developed based on the case of forward scattering micro radar,considering the two-ray propagation model and area target model,and nonlinear change of observation angle as well as high order phase error.Furthermore,the analytical form of the received power from moving target has been obtained.Using the simulated forward scattering radar cross section,the received power of theoretical calculation is near to that of measured data.In addition,the simulated signal model of ground moving target is perfectly matched with the experimented data.All these results show the correctness of analytical calculation completely.

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

    Science.gov (United States)

    Xu, Jia; Huang, Zuzhen; Yan, Liang; Zhou, Xu; Zhang, Furu; Long, Teng

    2016-10-12

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

  4. Ground moving target geo-location from monocular camera mounted on a micro air vehicle

    Science.gov (United States)

    Guo, Li; Ang, Haisong; Zheng, Xiangming

    2011-08-01

    The usual approaches to unmanned air vehicle(UAV)-to-ground target geo-location impose some severe constraints to the system, such as stationary objects, accurate geo-reference terrain database, or ground plane assumption. Micro air vehicle(MAV) works with characteristics including low altitude flight, limited payload and onboard sensors' low accuracy. According to these characteristics, a method is developed to determine the location of ground moving target which imaged from the air using monocular camera equipped on MAV. This method eliminates the requirements for terrain database (elevation maps) and altimeters that can provide MAV's and target's altitude. Instead, the proposed method only requires MAV flight status provided by its inherent onboard navigation system which includes inertial measurement unit(IMU) and global position system(GPS). The key is to get accurate information on the altitude of the ground moving target. First, Optical flow method extracts background static feature points. Setting a local region around the target in the current image, The features which are on the same plane with the target in this region are extracted, and are retained as aided features. Then, inverse-velocity method calculates the location of these points by integrated with aircraft status. The altitude of object, which is calculated by using position information of these aided features, combining with aircraft status and image coordinates, geo-locate the target. Meanwhile, a framework with Bayesian estimator is employed to eliminate noise caused by camera, IMU and GPS. Firstly, an extended Kalman filter(EKF) provides a simultaneous localization and mapping solution for the estimation of aircraft states and aided features location which defines the moving target local environment. Secondly, an unscented transformation(UT) method determines the estimated mean and covariance of target location from aircraft states and aided features location, and then exports them for the

  5. Special Operations Forces and Elusive Enemy Ground Targets: Lessons from Vietnam and the Persian Gulf War

    Science.gov (United States)

    2001-01-01

    Enemy Ground Targets team members to fire their weapons as they were lifted from the forest floor . 4 9 Moving through and searching the jungle...MACVSOG headquarters, and as bartenders and waitresses at MACVSOG compounds, where they 61Prados, Blood Road, p. 274. Yearly totals for SHINING BRASS

  6. Genome-wide identification of direct HBx genomic targets

    KAUST Repository

    Guerrieri, Francesca

    2017-02-17

    Background The Hepatitis B Virus (HBV) HBx regulatory protein is required for HBV replication and involved in HBV-related carcinogenesis. HBx interacts with chromatin modifying enzymes and transcription factors to modulate histone post-translational modifications and to regulate viral cccDNA transcription and cellular gene expression. Aiming to identify genes and non-coding RNAs (ncRNAs) directly targeted by HBx, we performed a chromatin immunoprecipitation sequencing (ChIP-Seq) to analyse HBV recruitment on host cell chromatin in cells replicating HBV. Results ChIP-Seq high throughput sequencing of HBx-bound fragments was used to obtain a high-resolution, unbiased, mapping of HBx binding sites across the genome in HBV replicating cells. Protein-coding genes and ncRNAs involved in cell metabolism, chromatin dynamics and cancer were enriched among HBx targets together with genes/ncRNAs known to modulate HBV replication. The direct transcriptional activation of genes/miRNAs that potentiate endocytosis (Ras-related in brain (RAB) GTPase family) and autophagy (autophagy related (ATG) genes, beclin-1, miR-33a) and the transcriptional repression of microRNAs (miR-138, miR-224, miR-576, miR-596) that directly target the HBV pgRNA and would inhibit HBV replication, contribute to HBx-mediated increase of HBV replication. Conclusions Our ChIP-Seq analysis of HBx genome wide chromatin recruitment defined the repertoire of genes and ncRNAs directly targeted by HBx and led to the identification of new mechanisms by which HBx positively regulates cccDNA transcription and HBV replication.

  7. High-speed ground moving target detection research using triangular modulation FMCW

    Institute of Scientific and Technical Information of China (English)

    Yi LIANG; Long ZHANG; Mengdao XING; Zheng BAO

    2009-01-01

    The frequency modulated continuous wave (FMCW) radar has the characteristics of low probability of interception, good hidden property and the ability to counter anti-radiation missiles. This paper proposes a new method for high-speed ground moving target detection (GMTD) using triangular modulation FMCW. According to the characteristic of the opposite range shift induced by the upslope and downslope modulation FMCW, the upslope and downslope are imaged, respectively. After compensation of continuous motion of the platform and time difference between upslope and downslope signals for imaging, the moving target can be detected through displaced phase center antenna (DPCA) technology.When the moving target is detected, the moving target image is extracted, and correlation processing is used to obtain the range shift, which can be used to estimate the target radial velocity, and further to find the real position of the target. The effectiveness of this method is verified by the result of computer simulation.

  8. Instrumented borehole drilling for interface identification in intricate weathered granite ground engineering

    Institute of Scientific and Technical Information of China (English)

    Zhuoying Tan; Meifeng Cai; Z.Q. Yue; L.G.Tham; C.F.Lee

    2007-01-01

    The successful application in drilling for HK simple weathered granite foundation has revealed its further use in instrumented drilling system as a ground investigation tool in the detection of other lithology formations, geohazards, underground water, and boundary of orebody. To expand the further use and test the accuracy in identification of formation, an R-20 rotary-hydraulic drill rig was instrumented with a digital drilling process monitoring system (DPM) for drilling in an intricate decomposed granite site.In this test ground, the boreholes revealed that the weathered granite alternately changes between moderate and strong. The qualitative and quantitative analysis of the penetrating parameters, indicates the effective thrust force, rotary speed, flushing pressure, penetrating rate, and displacement of the bit fluctuate at ground interfaces. It shows that the parameters get a good response with the change of rock strength at the interfaces, which can reveal the change of the intricate granite formation. Besides, a variable-slope method has been established, for identification of dominative and subsidiary interfaces in the granite site. The result from a t-test shows that the confidence of the instrumented drilling system in identification of the geotechnical interfaces is up to 99%.

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

    Directory of Open Access Journals (Sweden)

    Jia Xu

    2016-10-01

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

  10. Ground target localization algorithm for semi-active laser terminal correction projectile

    Directory of Open Access Journals (Sweden)

    Xing-long Li

    2016-06-01

    Full Text Available A target localization algorithm, which uses the measurement information from onboard GPS and onboard laser detector to acquire the target position, is proposed to obtain the accurate position of ground target in real time in the trajectory correction process of semi-active laser terminal correction projectile. A target localization model is established according to projectile position, attitude and line-of-sight angle. The effects of measurement errors of projectile position, attitude and line-of-sight angle on localization accuracy at different quadrant elevation angles are analyzed through Monte-Carlo simulation. The simulation results show that the measurement error of line-of-sight angle has the largest influence on the localization accuracy. The localization accuracy decreases with the increase in quadrant elevation angle. However, the maximum localization accuracy is less than 7 m. The proposed algorithm meets the accuracy and real-time requirements of target localization.

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

    Science.gov (United States)

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

    2016-07-19

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

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

    Directory of Open Access Journals (Sweden)

    Sungho Kim

    2016-07-01

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

  13. Estimation of detection threshold in multiple ship target situations with HF ground wave radar

    Institute of Scientific and Technical Information of China (English)

    Li Hongbo; Shen Yiying; Liu Yongtan

    2007-01-01

    A credible method of calculating the detection threshold is presented for the multiple target situations,which appear frequently in the lower Doppler velocity region during the surveillance of sea with HF ground wave radar. This method defines a whole-peak-outlier elimination (WPOE) criterion, which is based on in-peak-samples correlation of each target echo spectra, to trim off the target signals and abnormal disturbances with great amplitude from the complex spectra. Therefore, cleaned background noise samples are obtained to improve the accuracy and reliability of noise level estimation. When the background noise is nonhomogeneous, the detection samples are limited and often occupied heavily with outliers. In this case, the problem that the detection threshold is overvalued can be solved. In applications on experimental data, it is verified that this method can reduce the miss alarm rate of signal detection effectively in multiple target situations as well as make the adaptability of the detector better.

  14. Integrated Guidance and Control of Homing Missiles Against Ground Fixed Targets

    Institute of Scientific and Technical Information of China (English)

    Hou Mingzhe; Duan Guangren

    2008-01-01

    This paper presents a scheme of integrated guidance and autopilot design for homing missiles against ground fixed targets. An in- tegrated guidance and control model in the pitch plane is formulated and further changed into a normal form by nonlinear coordinate transformation. By adopting the sliding mode control approach, an adaptive nonlinear control law of the system is designed so that the missile can hit the target accurately with a desired impact attitude angle. The stability analysis of the closed-loop system is also con- ducted. The numerical simulation has confirmed the usefulness of the proposed design scheme.

  15. Air-to-Ground Target Acquisition Source Book: A Review of the Literature

    Science.gov (United States)

    1974-09-30

    its backgrotnid. Middleton (1936) studied the applicability of the C.I.E. metric to that of colored point sources. Konchmieder ( 1924 ) thought that...igated in two studieu per- formed by Rusia , Snyder, and GreeninE, (965u) and Rusis, Snyder, Greening, and Rawlingg (1965b), which repreosent exp erionto...acquisition of ground targets by observers in low-leve: high-speed aircraft. Sandia Laboratory, Albuquerque, New Mexico , SC-TM-66-54, February 1966

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

    Science.gov (United States)

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

    2008-09-01

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

  17. An in silico target identification using Boolean network attractors: Avoiding pathological phenotypes.

    Science.gov (United States)

    Poret, Arnaud; Boissel, Jean-Pierre

    2014-12-01

    Target identification aims at identifying biomolecules whose function should be therapeutically altered to cure the considered pathology. An algorithm for in silico target identification using Boolean network attractors is proposed. It assumes that attractors correspond to phenotypes produced by the modeled biological network. It identifies target combinations which allow disturbed networks to avoid attractors associated with pathological phenotypes. The algorithm is tested on a Boolean model of the mammalian cell cycle and its applications are illustrated on a Boolean model of Fanconi anemia. Results show that the algorithm returns target combinations able to remove attractors associated with pathological phenotypes and then succeeds in performing the proposed in silico target identification. However, as with any in silico evidence, there is a bridge to cross between theory and practice. Nevertheless, it is expected that the algorithm is of interest for target identification.

  18. PBIT: pipeline builder for identification of drug targets for infectious diseases.

    Science.gov (United States)

    Shende, Gauri; Haldankar, Harshala; Barai, Ram Shankar; Bharmal, Mohammed Husain; Shetty, Vinit; Idicula-Thomas, Susan

    2016-12-30

    PBIT (Pipeline Builder for Identification of drug Targets) is an online webserver that has been developed for screening of microbial proteomes for critical features of human drug targets such as being non-homologous to human proteome as well as the human gut microbiota, essential for the pathogen's survival, participation in pathogen-specific pathways etc. The tool has been validated by analyzing 57 putative targets of Candida albicans documented in literature. PBIT integrates various in silico approaches known for drug target identification and will facilitate high-throughput prediction of drug targets for infectious diseases, including multi-pathogenic infections.

  19. Experimental identification of microRNA-140 targets by silencing and overexpressing miR-140

    DEFF Research Database (Denmark)

    Nicolas, Francisco Esteban; Pais, Helio; Schwach, Frank

    2008-01-01

    MicroRNAs (miRNAs) are short noncoding RNA molecules regulating the expression of mRNAs. Target identification of miRNAs is computationally difficult due to the relatively low homology between miRNAs and their targets. We present here an experimental approach to target identification where the ca...... on the presence of the seed sequence. Interestingly, none of these were predicted by the published target prediction methods we used. One of the potential target mRNAs, Cxcl12, was experimentally validated by Northern blot analysis and a luciferase reporter assay....

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

    Science.gov (United States)

    2009-03-01

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

  1. Theoretical Grounds of Identification of the Essence of the Enterprise Development Efficiency Category

    Directory of Open Access Journals (Sweden)

    Adzhavenko Maryna M.

    2014-02-01

    Full Text Available Modern economic conditions put a new problem in front of scientists, namely: capability of an enterprise to survive in the unfavourable external environment. This problem is a system and complex one and its solution is within the plane of management of capital, personnel, development, efficiency, etc. The article marks out that efficiency is a corner stone of the modern economic science, which justifies studies of the gnoseological essence of the efficiency category. The main goal of the article lies in the study of scientific and theoretical grounds of formation of the enterprise development efficiency under modern conditions of the changing internal and external environments. The other goals of the article are identification of the essence of the development efficiency category, deepening the theoretical foundation of assessment of efficiency of enterprise development in the modern economic science. The article conducts an ontological analysis of the essence and goals of the enterprise development efficiency notion, studies evolution of scientific approaches and systemises theoretical provisions of the specified category and their assessment in the economic science. In the result of the study the article identifies a new vector of theoretical grounds and dominating logic of formation of the methodology of assessment of efficiency of enterprises under conditions of innovation development of the state, namely: it underlines principles of systemacy, complexity, self-organisation, significance of human capital as an important factor of increase of efficiency and development. Development of methodological grounds of assessment of efficiency of enterprise innovation development is a prospective direction of further studies.

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

    Science.gov (United States)

    2014-03-27

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

  3. Person re-identification across aerial and ground-based cameras by deep feature fusion

    Science.gov (United States)

    Schumann, Arne; Metzler, Jürgen

    2017-05-01

    Person re-identification is the task of correctly matching visual appearances of the same person in image or video data while distinguishing appearances of different persons. The traditional setup for re-identification is a network of fixed cameras. However, in recent years mobile aerial cameras mounted on unmanned aerial vehicles (UAV) have become increasingly useful for security and surveillance tasks. Aerial data has many characteristics different from typical camera network data. Thus, re-identification approaches designed for a camera network scenario can be expected to suffer a drop in accuracy when applied to aerial data. In this work, we investigate the suitability of features, which were shown to give robust results for re- identification in camera networks, for the task of re-identifying persons between a camera network and a mobile aerial camera. Specifically, we apply hand-crafted region covariance features and features extracted by convolu- tional neural networks which were learned on separate data. We evaluate their suitability for this new and as yet unexplored scenario. We investigate common fusion methods to combine the hand-crafted and learned features and propose our own deep fusion approach which is already applied during training of the deep network. We evaluate features and fusion methods on our own dataset. The dataset consists of fourteen people moving through a scene recorded by four fixed ground-based cameras and one mobile camera mounted on a small UAV. We discuss strengths and weaknesses of the features in the new scenario and show that our fusion approach successfully leverages the strengths of each feature and outperforms all single features significantly.

  4. Identification of air and sea-surface targets with a laser range profiler

    NARCIS (Netherlands)

    Heuvel, J.C. van den; Schoemaker, R.M.; Schleijpen, H.M.A.

    2009-01-01

    Current coastal operations have to deal with threats at short range in complex environments with both neutral and hostile targets. There is a need for fast identification, which is possible with a laser range profiler. A number of field trials have been conducted to validate the concept of identific

  5. A new disaster victim identification management strategy targeting "near identification-threshold" cases: Experiences from the Boxing Day tsunami.

    Science.gov (United States)

    Wright, Kirsty; Mundorff, Amy; Chaseling, Janet; Forrest, Alexander; Maguire, Christopher; Crane, Denis I

    2015-05-01

    The international disaster victim identification (DVI) response to the Boxing Day tsunami, led by the Royal Thai Police in Phuket, Thailand, was one of the largest and most complex in DVI history. Referred to as the Thai Tsunami Victim Identification operation, the group comprised a multi-national, multi-agency, and multi-disciplinary team. The traditional DVI approach proved successful in identifying a large number of victims quickly. However, the team struggled to identify certain victims due to incomplete or poor quality ante-mortem and post-mortem data. In response to these challenges, a new 'near-threshold' DVI management strategy was implemented to target presumptive identifications and improve operational efficiency. The strategy was implemented by the DNA Team, therefore DNA kinship matches that just failed to reach the reporting threshold of 99.9% were prioritized, however the same approach could be taken by targeting, for example, cases with partial fingerprint matches. The presumptive DNA identifications were progressively filtered through the Investigation, Dental and Fingerprint Teams to add additional information necessary to either strengthen or conclusively exclude the identification. Over a five-month period 111 victims from ten countries were identified using this targeted approach. The new identifications comprised 87 adults, 24 children and included 97 Thai locals. New data from the Fingerprint Team established nearly 60% of the total near-threshold identifications and the combined DNA/Physical method was responsible for over 30%. Implementing the new strategy, targeting near-threshold cases, had positive management implications. The process initiated additional ante-mortem information collections, and established a much-needed, distinct "end-point" for unresolved cases. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  6. Seismic Target Classification Using a Wavelet Packet Manifold in Unattended Ground Sensors Systems

    Directory of Open Access Journals (Sweden)

    Enliang Song

    2013-07-01

    Full Text Available One of the most challenging problems in target classification is the extraction of a robust feature, which can effectively represent a specific type of targets. The use of seismic signals in unattended ground sensor (UGS systems makes this problem more complicated, because the seismic target signal is non-stationary, geology-dependent and with high-dimensional feature space. This paper proposes a new feature extraction algorithm, called wavelet packet manifold (WPM, by addressing the neighborhood preserving embedding (NPE algorithm of manifold learning on the wavelet packet node energy (WPNE of seismic signals. By combining non-stationary information and low-dimensional manifold information, WPM provides a more robust representation for seismic target classification. By using a K nearest neighbors classifier on the WPM signature, the algorithm of wavelet packet manifold classification (WPMC is proposed. Experimental results show that the proposed WPMC can not only reduce feature dimensionality, but also improve the classification accuracy up to 95.03%. Moreover, compared with state-of-the-art methods, WPMC is more suitable for UGS in terms of recognition ratio and computational complexity.

  7. Application of star identification using pattern matching to space ground systems at GSFC

    Science.gov (United States)

    Fink, D.; Shoup, D.

    1994-01-01

    This paper reports the application of pattern recognition techniques for star identification based on those proposed by Van Bezooijen to space ground systems for near-real-time attitude determination. A prototype was developed using these algorithms, which was used to assess the suitability of these techniques for support of the X-Ray Timing Explorer (XTE), Submillimeter Wave Astronomy Satellite (SWAS), and the Solar and Heliospheric Observatory (SOHO) missions. Experience with the prototype was used to refine specifications for the operational system. Different geometry tests appropriate to the mission requirements of XTE, SWAS, and SOHO were adopted. The applications of these techniques to upcoming mission support of XTE, SWAS, and SOHO are discussed.

  8. Target Identification for CNS Diseases by Transcriptional Profiling

    OpenAIRE

    Altar, C. Anthony; Vawter, Marquis P.; Ginsberg, Stephen D.

    2008-01-01

    Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human postmortem brain, animal models, and cell culture studies. Analysis of isolated human neurons implicates targets for Alzheimer’s disease and the cognitive decline associated with normal aging and mild ...

  9. The gamma Dor CoRoT target HD49434. I-Results from the ground-based campaign

    CERN Document Server

    Uytterhoeven, K; Poretti, E; Rainer, M; Martin-Ruiz, S; Rodríguez, E; Amado, P J; LeContel, D; Jankov, S; Niemczura, E; Pollard, K; Brunsden, E; Paparo, M; Costa, V; Valtier, J -C; Garrido, R; Marin, A J; Suárez, J C; Kilmartin, P H; Chapellier, E; Rodriguez-Lopez, C; Aceituno, F J; Casanova, V; Rolland, A; Olivares, I

    2008-01-01

    Context: We present the results of an extensive ground-based photometric and spectroscopic campaign on the gamma Dor CoRoT target HD49434. This campaign was preparatory to the CoRoT satellite observations, which took place from October 2007 to March 2008. Results: The frequency analysis clearly shows the presence of four frequencies in the 0.2-1.7 c/d interval, as well as six frequencies in the 5-12 c/d domain. The low frequencies are typical for gamma Dor variables while the high frequencies are common for delta Sct pulsators. We propose the frequency 2.666 c/d as a possible rotational frequency. All modes, for which an identification was possible, seem to be high-degree modes (3 <= l <= 8). We did not find evidence for a possible binary nature of HD49434. The element abundances we derived are consistent with the values obtained in previous analyses. Conclusions: We classify the gamma Dor star HD49434 as a hybrid pulsator, which pulsates simultaneously in p- and g-modes. This finding makes HD49434 an e...

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

    NARCIS (Netherlands)

    Zaugg, S.; Saporta, G.; van Loon, E.; Schmaljohann, H.; Liechti, F.

    2008-01-01

    Bird identification with radar is important for bird migration research, environmental impact assessments (e.g. wind farms), aircraft security and radar meteorology. In a study on bird migration, radar signals from birds, insects and ground clutter were recorded. Signals from birds show a typical

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

    NARCIS (Netherlands)

    Zaugg, S.; Saporta, G.; van Loon, E.; Schmaljohann, H.; Liechti, F.

    2008-01-01

    Bird identification with radar is important for bird migration research, environmental impact assessments (e.g. wind farms), aircraft security and radar meteorology. In a study on bird migration, radar signals from birds, insects and ground clutter were recorded. Signals from birds show a typical pa

  12. Passive Synthetic Aperture Hitchhiker Imaging of Ground Moving Targets - Part 2: Performance Analysis.

    Science.gov (United States)

    Wacks, Steven; Yazici, Birsen

    2014-07-08

    In Part 1 of this work, we present a passive synthetic aperture imaging and velocity estimation method for ground moving targets using a network of passive receivers. The method involves inversion of a Radon transform type forward model via a novel filtered backprojection approach combined with entropy optimization. The method is applicable to noncooperative transmitters of opportunity where the transmitter locations and transmitted waveforms are unknown. Furthermore, it can image multiple targets moving at different velocities in arbitrary imaging geometries. In this paper, we present a detailed analysis of the performance of our method. First the resolution analysis in position and velocity spaces is presented. The analysis identifies several factors that contribute positively or negativity towards position and velocity resolution. Next, we present a novel theory to analyze and predict smearing artifacts in position images due to error in velocity estimation of moving targets. Specifically, we show that small errors in the velocity estimation result in small positioning errors. We present extensive numerical simulations to demonstrate the theoretical results. While our primary interest lies in radar, the theory, methods and algorithms introduced in our work are also applicable to passive acoustic, seismic, and microwave imaging.

  13. Detection of Ground Moving Targets for Two-Channel Spaceborne SAR-ATI

    Directory of Open Access Journals (Sweden)

    Diannong Liang

    2010-01-01

    Full Text Available Many present spaceborne synthetic aperture radar (SAR systems are constrained to only two channels for ground moving target indication (GMTI. Along-track interferometry (ATI technique is currently exploited to detect slowly moving targets and measure their radial velocity and azimuth real position. In this paper, based on the joint probability density function (PDF of interferogram's phase and amplitude and the two hypotheses “clutter” and “clutter plus signal”, several constant false alarm rate (CFAR detection criteria are analyzed for their capabilities and limitations under low signal-to-clutter ratio (SCR and low clutter-to-noise ratio (CNR conditions. The CFAR detectors include one-step CFAR detector with interferometric phase, two-step CFAR detectors, and two-dimensional (2D CFAR detector. The likelihood ratio test (LRT based on the Neyman-Pearson (NP criterion is exploited as an upper bound for the performance of the other CFAR detectors. Performance analyses demonstrate the superiority of the 2D CFAR techniques to detect dim slowly moving targets for spaceborne system.

  14. Tackling the vascular heterogeneity issue in tumors : identification of novel targets for tumor therapy

    NARCIS (Netherlands)

    Roodink, I.

    2009-01-01

    This thesis focuses on the identification of novel vascular targeting agents directed against tumor endothelium and the expression patterns of their targets in (clinical) tumor samples. Tumors obtain their blood supply by the formation of new vessels and/or by the incorporation, and possibly

  15. Identification of Thioredoxin Target Disulfides Using Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2014-01-01

    extracts is described. The procedure utilizes the isotope-coded affinity tag (ICAT) reagents containing a thiol reactive iodoacetamide group and a biotin affinity tag to target peptides containing reduced cysteine residues. The identification of substrates for Trx and the extent of target disulfide...

  16. Tackling the vascular heterogeneity issue in tumors : identification of novel targets for tumor therapy

    NARCIS (Netherlands)

    Roodink, I.

    2009-01-01

    This thesis focuses on the identification of novel vascular targeting agents directed against tumor endothelium and the expression patterns of their targets in (clinical) tumor samples. Tumors obtain their blood supply by the formation of new vessels and/or by the incorporation, and possibly subsequ

  17. Unsupervised learning in persistent sensing for target recognition by wireless ad hoc networks of ground-based sensors

    Science.gov (United States)

    Hortos, William S.

    2008-04-01

    In previous work by the author, effective persistent and pervasive sensing for recognition and tracking of battlefield targets were seen to be achieved, using intelligent algorithms implemented by distributed mobile agents over a composite system of unmanned aerial vehicles (UAVs) for persistence and a wireless network of unattended ground sensors for pervasive coverage of the mission environment. While simulated performance results for the supervised algorithms of the composite system are shown to provide satisfactory target recognition over relatively brief periods of system operation, this performance can degrade by as much as 50% as target dynamics in the environment evolve beyond the period of system operation in which the training data are representative. To overcome this limitation, this paper applies the distributed approach using mobile agents to the network of ground-based wireless sensors alone, without the UAV subsystem, to provide persistent as well as pervasive sensing for target recognition and tracking. The supervised algorithms used in the earlier work are supplanted by unsupervised routines, including competitive-learning neural networks (CLNNs) and new versions of support vector machines (SVMs) for characterization of an unknown target environment. To capture the same physical phenomena from battlefield targets as the composite system, the suite of ground-based sensors can be expanded to include imaging and video capabilities. The spatial density of deployed sensor nodes is increased to allow more precise ground-based location and tracking of detected targets by active nodes. The "swarm" mobile agents enabling WSN intelligence are organized in a three processing stages: detection, recognition and sustained tracking of ground targets. Features formed from the compressed sensor data are down-selected according to an information-theoretic algorithm that reduces redundancy within the feature set, reducing the dimension of samples used in the target

  18. Aircraft target identification based on 2D ISAR images using multiresolution analysis wavelet

    Science.gov (United States)

    Fu, Qiang; Xiao, Huaitie; Hu, Xiangjiang

    2001-09-01

    The formation of 2D ISAR images for radar target identification hold much promise for additional distinguish- ability between targets. Since an image contains important information is a wide range of scales, and this information is often independent from one scale to another, wavelet analysis provides a method of identifying the spatial frequency content of an image and the local regions within the image where those spatial frequencies exist. In this paper, a multiresolution analysis wavelet method based on 2D ISAR images was proposed for use in aircraft radar target identification under the wide band high range resolution radar background. The proposed method was performed in three steps; first, radar backscatter signals were processed in the form of 2D ISAR images, then, Mallat's wavelet algorithm was used in the decomposition of images, finally, a three layer perceptron neural net was used as classifier. The result of experiments demonstrated that the feasibility of using multiresolution analysis wavelet for target identification.

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

    Energy Technology Data Exchange (ETDEWEB)

    Doerry, Armin Walter

    2010-09-01

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

  20. Ground target detection based on discrete cosine transform and Rényi entropy for imaging ladar

    Science.gov (United States)

    Xu, Yuannan; Chen, Weili; Li, Junwei; Dong, Yanbing

    2016-01-01

    The discrete cosine transform (DCT) due to its excellent properties that the images can be represented in spatial/spatial-frequency domains, has been applied in sequence data analysis and image fusion. For intensity and range images of ladar, through the DCT using one dimension window, the statistical property of Rényi entropy for images is studied. We also analyzed the change of Rényi entropy's statistical property in the ladar intensity and range images when the man-made objects appear. From this foundation, a novel method for generating saliency map based on DCT and Rényi entropy is proposed. After that, ground target detection is completed when the saliency map is segmented using a simple and convenient threshold method. For the ladar intensity and range images, experimental results show the proposed method can effectively detect the military vehicles from complex earth background with low false alarm.

  1. Target identification of natural products and bioactive compounds using affinity-based probes.

    Science.gov (United States)

    Pan, Sijun; Zhang, Hailong; Wang, Chenyu; Yao, Samantha C L; Yao, Shao Q

    2016-05-04

    Covering: 2010 to 2014.Advances in isolation, synthesis and screening strategies have made many bioactive substances available. However, in most cases their putative biological targets remain unknown. Herein, we highlight recent advances in target identification of natural products and bioactive compounds by using affinity-based probes. Aided by photoaffinity labelling, this strategy can capture potential cellular targets (on and off) of a natural product or bioactive compound in live cells directly, even when the compound-target interaction is reversible with moderate affinity. The knowledge of these targets may help uncover molecular pathways and new therapeutics for currently untreatable diseases. In this highlight, we will introduce the development of various photoactivatable groups, their synthesis and applications in target identification of natural products and bioactive compounds, with a focus on work done in recent years and from our laboratory. We will further discuss the strengths and weaknesses of each group and the outlooks for this novel proteome-wide profiling strategy.

  2. Identification of potential glucocorticoid receptor therapeutic targets in multiple myeloma.

    Science.gov (United States)

    Thomas, Alexandra L; Coarfa, Cristian; Qian, Jun; Wilkerson, Joseph J; Rajapakshe, Kimal; Krett, Nancy L; Gunaratne, Preethi H; Rosen, Steven T

    2015-01-01

    Glucocorticoids (GC) are a cornerstone of combination therapies for multiple myeloma. However, patients ultimately develop resistance to GCs frequently based on decreased glucocorticoid receptor (GR) expression. An understanding of the direct targets of GC actions, which induce cell death, is expected to culminate in potential therapeutic strategies for inducing cell death by regulating downstream targets in the absence of a functional GR. The specific goal of our research is to identify primary GR targets that contribute to GC-induced cell death, with the ultimate goal of developing novel therapeutics around these targets that can be used to overcome resistance to GCs in the absence of GR. Using the MM.1S glucocorticoid-sensitive human myeloma cell line, we began with the broad platform of gene expression profiling to identify glucocorticoid-regulated genes further refined by combination treatment with phosphatidylinositol-3'-kinase inhibition (PI3Ki). To further refine the search to distinguish direct and indirect targets of GR that respond to the combination GC and PI3Ki treatment of MM.1S cells, we integrated 1) gene expression profiles of combination GC treatment with PI3Ki, which induces synergistic cell death; 2) negative correlation between genes inhibited by combination treatment in MM.1S cells and genes over-expressed in myeloma patients to establish clinical relevance and 3) GR chromatin immunoprecipitation with massively parallel sequencing (ChIP-Seq) in myeloma cells to identify global chromatin binding for the glucocorticoid receptor (GR). Using established bioinformatics platforms, we have integrated these data sets to identify a subset of candidate genes that may form the basis for a comprehensive picture of glucocorticoid actions in multiple myeloma. As a proof of principle, we have verified two targets, namely RRM2 and BCL2L1, as primary functional targets of GR involved in GC-induced cell death.

  3. Genome-wide identification of KANADI1 target genes.

    Directory of Open Access Journals (Sweden)

    Paz Merelo

    Full Text Available Plant organ development and polarity establishment is mediated by the action of several transcription factors. Among these, the KANADI (KAN subclade of the GARP protein family plays important roles in polarity-associated processes during embryo, shoot and root patterning. In this study, we have identified a set of potential direct target genes of KAN1 through a combination of chromatin immunoprecipitation/DNA sequencing (ChIP-Seq and genome-wide transcriptional profiling using tiling arrays. Target genes are over-represented for genes involved in the regulation of organ development as well as in the response to auxin. KAN1 affects directly the expression of several genes previously shown to be important in the establishment of polarity during lateral organ and vascular tissue development. We also show that KAN1 controls through its target genes auxin effects on organ development at different levels: transport and its regulation, and signaling. In addition, KAN1 regulates genes involved in the response to abscisic acid, jasmonic acid, brassinosteroids, ethylene, cytokinins and gibberellins. The role of KAN1 in organ polarity is antagonized by HD-ZIPIII transcription factors, including REVOLUTA (REV. A comparison of their target genes reveals that the REV/KAN1 module acts in organ patterning through opposite regulation of shared targets. Evidence of mutual repression between closely related family members is also shown.

  4. Molecular Methods for Identification of Clostridium tetani by Targeting Neurotoxin.

    Science.gov (United States)

    Nagoba, Basavraj; Dharne, Mahesh; Gohil, Kushal N

    2017-01-01

    Tetanus is a potentially fatal muscle spasm disease. It is an important public health problem, especially in rural/tribal areas of developing countries. Tetanus toxin, a neurotoxin (tetanospasmin ), is the most important virulence factor that plays a key role in the pathogenicity of tetanus . Confirmation of virulence by confirming the production of tetanospasmin by infecting species forms the most important part in the diagnosis of tetanus . Various molecular methods have been devised for confirmation of diagnosis by targeting different genes. The most common molecular methods are tetanospasmin producing (TetX) gene-targeted methods using TetX-specific primers. Here, we describe various molecular methods targeting TetX gene such as polymerase chain reaction, pulsed-field gel electrophoresis, Southern blotting, loop-mediated isothermal amplification assay, etc. to confirm the virulence of Cl. tetani.

  5. Drug target identification using side-effect similarity

    DEFF Research Database (Denmark)

    Campillos, Monica; Kuhn, Michael; Gavin, Anne-Claude

    2008-01-01

    Targets for drugs have so far been predicted on the basis of molecular or cellular features, for example, by exploiting similarity in chemical structure or in activity across cell lines. We used phenotypic side-effect similarities to infer whether two drugs share a target. Applied to 746 marketed...... drugs, a network of 1018 side effect-driven drug-drug relations became apparent, 261 of which are formed by chemically dissimilar drugs from different therapeutic indications. We experimentally tested 20 of these unexpected drug-drug relations and validated 13 implied drug-target relations by in vitro...... binding assays, of which 11 reveal inhibition constants equal to less than 10 micromolar. Nine of these were tested and confirmed in cell assays, documenting the feasibility of using phenotypic information to infer molecular interactions and hinting at new uses of marketed drugs....

  6. Divergent synthesis and identification of the cellular targets of deoxyelephantopins

    Science.gov (United States)

    Lagoutte, Roman; Serba, Christelle; Abegg, Daniel; Hoch, Dominic G.; Adibekian, Alexander; Winssinger, Nicolas

    2016-08-01

    Herbal extracts containing sesquiterpene lactones have been extensively used in traditional medicine and are known to be rich in α,β-unsaturated functionalities that can covalently engage target proteins. Here we report synthetic methodologies to access analogues of deoxyelephantopin, a sesquiterpene lactone with anticancer properties. Using alkyne-tagged cellular probes and quantitative proteomics analysis, we identified several cellular targets of deoxyelephantopin. We further demonstrate that deoxyelephantopin antagonizes PPARγ activity in situ via covalent engagement of a cysteine residue in the zinc-finger motif of this nuclear receptor.

  7. Ground-based integrated path coherent differential absorption lidar measurement of CO2: foothill target return

    Directory of Open Access Journals (Sweden)

    S. Ishii

    2013-05-01

    Full Text Available The National Institute of Information and Communications Technology (NICT has made a great deal of effort to develop a coherent 2 μm differential absorption and wind lidar (Co2DiaWiL for measuring CO2 and wind speed. First, coherent Integrated Path Differential Absorption (IPDA lidar experiments were conducted using the Co2DiaWiL and a foothill target (tree and ground surface located about 7.12 km south of NICT on 11, 27, and 28 December 2010. The detection sensitivity of a 2 μm IPDA lidar was examined in detail using the CO2 concentration measured by the foothill reflection. The precisions of CO2 measurements for the foothill target and 900, 4500 and 27 000 shot pairs were 6.5, 2.8, and 1.2%, respectively. The results indicated that a coherent IPDA lidar with a laser operating at a high pulse repetition frequency of a few tens of KHz is necessary for XCO2 (column-averaged dry air mixing ratio of CO2 measurement with a precision of 1–2 ppm in order to observe temporal and spatial variations in the CO2. Statistical comparisons indicated that, although a small amount of in situ data and the fact that they were not co-located with the foothill target made comparison difficult, the CO2 volume mixing ratio obtained by the Co2DiaWiL measurements for the foothill target and atmospheric returns was about −5 ppm lower than the 5 min running averages of the in situ sensor. Not only actual difference of sensing volume or the natural variability of CO2 but also the fluctuations of temperature could cause this difference. The statistical results indicated that there were no biases between the foothill target and atmospheric return measurements. The 2 μm coherent IPDA lidar can detect the CO2 volume mixing ratio change of 3% in the 5 min signal integration. In order to detect the position of the foothill target, to measure a range with a high SNR (signal-to-noise ratio, and to reduce uncertainty due to the presence of aerosols and clouds, it is

  8. Fixation-related potentials : Foveal versus parafoveal target identification

    NARCIS (Netherlands)

    Brouwer, A.M.; Brinkhuis, M.A.B.; Reuderink, B.; Hogervorst, M.A.; Erp, J.B.F. van

    2014-01-01

    The P300 event-related potential (ERP) can be used to infer whether an observer is looking at a target or not. Common practice in P300 BCIs and experiments is that observers are asked to fixate their eyes while stimuli are presented. First studies have shown that it is also possible to distinguish

  9. Identification of novel targets in prostate cancer progression

    NARCIS (Netherlands)

    Ghotra, Veerander Paul Singh

    2013-01-01

    We have developed novel fluorescence bio-imaging based automated models to screen for novel candidate targets involved in prostate cancer metastasis. Utilizing these models and adopting a functional genomics based approach; we identified SYK as a novel regulator of prostate cancer progression. We al

  10. Combinatorial approaches for the identification of brain drug delivery targets.

    Science.gov (United States)

    Stutz, Charles C; Zhang, Xiaobin; Shusta, Eric V

    2014-01-01

    The blood-brain barrier (BBB) represents a large obstacle for the treatment of central nervous system diseases. Targeting endogenous nutrient transporters that transcytose the BBB is one promising approach to selectively and noninvasively deliver a drug payload to the brain. The main limitations of the currently employed transcytosing receptors are their ubiquitous expression in the peripheral vasculature and the inherent low levels of transcytosis mediated by such systems. In this review, approaches designed to increase the repertoire of transcytosing receptors which can be targeted for the purpose of drug delivery are discussed. In particular, combinatorial protein libraries can be screened on BBB cells in vitro or in vivo to isolate targeting peptides or antibodies that can trigger transcytosis. Once these targeting reagents are discovered, the cognate BBB transcytosis system can be identified using techniques such as expression cloning or immunoprecipitation coupled with mass spectrometry. Continued technological advances in BBB genomics and proteomics, membrane protein manipulation, and in vitro BBB technology promise to further advance the capability to identify and optimize peptides and antibodies capable of mediating drug transport across the BBB.

  11. Target identification for CNS diseases by transcriptional profiling.

    Science.gov (United States)

    Altar, C Anthony; Vawter, Marquis P; Ginsberg, Stephen D

    2009-01-01

    Gene expression changes in neuropsychiatric and neurodegenerative disorders, and gene responses to therapeutic drugs, provide new ways to identify central nervous system (CNS) targets for drug discovery. This review summarizes gene and pathway targets replicated in expression profiling of human postmortem brain, animal models, and cell culture studies. Analysis of isolated human neurons implicates targets for Alzheimer's disease and the cognitive decline associated with normal aging and mild cognitive impairment. In addition to tau, amyloid-beta precursor protein, and amyloid-beta peptides (Abeta), these targets include all three high-affinity neurotrophin receptors and the fibroblast growth factor (FGF) system, synapse markers, glutamate receptors (GluRs) and transporters, and dopamine (DA) receptors, particularly the D2 subtype. Gene-based candidates for Parkinson's disease (PD) include the ubiquitin-proteosome system, scavengers of reactive oxygen species, brain-derived neurotrophic factor (BDNF), its receptor, TrkB, and downstream target early growth response 1, Nurr-1, and signaling through protein kinase C and RAS pathways. Increasing variability and decreases in brain mRNA production from middle age to old age suggest that cognitive impairments during normal aging may be addressed by drugs that restore antioxidant, DNA repair, and synaptic functions including those of DA to levels of younger adults. Studies in schizophrenia identify robust decreases in genes for GABA function, including glutamic acid decarboxylase, HINT1, glutamate transport and GluRs, BDNF and TrkB, numerous 14-3-3 protein family members, and decreases in genes for CNS synaptic and metabolic functions, particularly glycolysis and ATP generation. Many of these metabolic genes are increased by insulin and muscarinic agonism, both of which are therapeutic in psychosis. Differential genomic signals are relatively sparse in bipolar disorder, but include deficiencies in the expression of 14

  12. PDTD: a web-accessible protein database for drug target identification

    Directory of Open Access Journals (Sweden)

    Gao Zhenting

    2008-02-01

    Full Text Available Abstract Background Target identification is important for modern drug discovery. With the advances in the development of molecular docking, potential binding proteins may be discovered by docking a small molecule to a repository of proteins with three-dimensional (3D structures. To complete this task, a reverse docking program and a drug target database with 3D structures are necessary. To this end, we have developed a web server tool, TarFisDock (Target Fishing Docking http://www.dddc.ac.cn/tarfisdock, which has been used widely by others. Recently, we have constructed a protein target database, Potential Drug Target Database (PDTD, and have integrated PDTD with TarFisDock. This combination aims to assist target identification and validation. Description PDTD is a web-accessible protein database for in silico target identification. It currently contains >1100 protein entries with 3D structures presented in the Protein Data Bank. The data are extracted from the literatures and several online databases such as TTD, DrugBank and Thomson Pharma. The database covers diverse information of >830 known or potential drug targets, including protein and active sites structures in both PDB and mol2 formats, related diseases, biological functions as well as associated regulating (signaling pathways. Each target is categorized by both nosology and biochemical function. PDTD supports keyword search function, such as PDB ID, target name, and disease name. Data set generated by PDTD can be viewed with the plug-in of molecular visualization tools and also can be downloaded freely. Remarkably, PDTD is specially designed for target identification. In conjunction with TarFisDock, PDTD can be used to identify binding proteins for small molecules. The results can be downloaded in the form of mol2 file with the binding pose of the probe compound and a list of potential binding targets according to their ranking scores. Conclusion PDTD serves as a comprehensive and

  13. Assembly and clustering of natural antibiotics guides target identification.

    Science.gov (United States)

    Johnston, Chad W; Skinnider, Michael A; Dejong, Chris A; Rees, Philip N; Chen, Gregory M; Walker, Chelsea G; French, Shawn; Brown, Eric D; Bérdy, János; Liu, Dennis Y; Magarvey, Nathan A

    2016-04-01

    Antibiotics are essential for numerous medical procedures, including the treatment of bacterial infections, but their widespread use has led to the accumulation of resistance, prompting calls for the discovery of antibacterial agents with new targets. A majority of clinically approved antibacterial scaffolds are derived from microbial natural products, but these valuable molecules are not well annotated or organized, limiting the efficacy of modern informatic analyses. Here, we provide a comprehensive resource defining the targets, chemical origins and families of the natural antibacterial collective through a retrobiosynthetic algorithm. From this we also detail the directed mining of biosynthetic scaffolds and resistance determinants to reveal structures with a high likelihood of having previously unknown modes of action. Implementing this pipeline led to investigations of the telomycin family of natural products from Streptomyces canus, revealing that these bactericidal molecules possess a new antibacterial mode of action dependent on the bacterial phospholipid cardiolipin.

  14. Neural Network Target Identification System for False Alarm Reduction

    Science.gov (United States)

    Ye, David; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

    2009-01-01

    A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feed forward back propagation neural network (NN) is then trained to classify each feature vector and remove false positives. This paper discusses the test of the system performance and parameter optimizations process which adapts the system to various targets and datasets. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar image dataset.

  15. Neural Network Target Identification System for False Alarm Reduction

    Science.gov (United States)

    Ye, David; Edens, Weston; Lu, Thomas T.; Chao, Tien-Hsin

    2009-01-01

    A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feed forward back propagation neural network (NN) is then trained to classify each feature vector and remove false positives. This paper discusses the test of the system performance and parameter optimizations process which adapts the system to various targets and datasets. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar image dataset.

  16. Lineup identification accuracy: The effects of alcohol, target presence, confidence ratings, and response time

    Directory of Open Access Journals (Sweden)

    Wendy Kneller

    2016-01-01

    Full Text Available Despite the intoxication of many eyewitnesses at crime scenes, only four published studies to date have investigated the effects of alcohol intoxication on eyewitness identification performance. While one found intoxication significantly increased false identification rates from target absent showups, three found no such effect using the more traditional lineup procedure. The present study sought to further explore the effects of alcohol intoxication on identification performance and examine whether accurate decisions from intoxicated witnesses could be postdicted by confidence and response times. One hundred and twenty participants engaged in a study examining the effects of intoxication (control, placebo, and mild intoxication and target presence on identification performance. Participants viewed a simultaneous lineup one week after watching a mock crime video of a man attempting to steal cars. Ethanol intoxication (0.6 ml/kg was found to make no significant difference to identification accuracy and such identifications from intoxicated individuals were made no less confidently or slowly than those from sober witnesses. These results are discussed with respect to the previous research examining intoxicated witness identification accuracy and the misconceptions the criminal justice system holds about the accuracy of such witnesses.

  17. Identification of Conserved Cotton MicroRNAs and Their Targets

    Institute of Scientific and Technical Information of China (English)

    ZHANG Bao-hong; WANG Qing-lian

    2008-01-01

    @@ No study has been performed on identifying microRNAs (miRNAs) and their targets in cotton although cotton is one of the most important fiber and economic crops around the world.In this study,we found 30 potential cotton miRNAs using a comparative genomic approach based on genomic survey sequence analysis and miRNA secondary structure.These cotton miRNAs belong to 22 miRNA families.Expressed sequence tag (EST) analysis indicated that the predicted miRNAs were expressed in cotton plants.

  18. Determination of the effect of brand and product identification on consumer palatability ratings of ground beef patties.

    Science.gov (United States)

    Wilfong, A K; McKillip, K V; Gonzalez, J M; Houser, T A; Unruh, J A; Boyle, E A E; O'Quinn, T G

    2016-11-01

    The objective of this study was to determine the effect of brand and product identification on consumer palatability ratings of ground beef patties. Six treatments were used in the study: 90/10 Certified Angus Beef (CAB) ground sirloin, 90/10 ground beef, 80/20 CAB ground chuck, 80/20 ground chuck, 80/20 ground beef, and 73/27 CAB ground beef. Ground beef was processed into 151.2-g patties using a patty former with 2 consecutively formed patties assigned to blind consumer testing and the following 2 assigned to informed testing. Following cooking to 74°C, patties were cut into quarters and served to consumers. Consumers ( = 112) evaluated samples in 2 rounds for tenderness, juiciness, flavor liking, texture liking, and overall liking. Each trait was also rated as either acceptable or unacceptable. In the first round of testing, samples were blind evaluated, with no information about the treatments provided to consumers, but in the second round, product type and brand were disclosed prior to sample evaluation. Additionally, texture profile and shear force analyses were performed on patties from each treatment. Few differences were observed for palatability traits during blind consumer testing; however, during informed testing, 90/10 CAB ground sirloin was rated greatest ( brand disclosure. Increased ( branded product that received increased ( brand and product information, few consumers find differences in eating quality among ground beef treatments; however, when consumers are aware of the brand, fat level, and subprimal blend prior to sampling, these factors have a large impact on consumer eating satisfaction.

  19. Target identification for stereotactic thalamotomy using diffusion tractography.

    Directory of Open Access Journals (Sweden)

    Zsigmond Tamás Kincses

    Full Text Available BACKGROUND: Stereotactic targets for thalamotomy are usually derived from population-based coordinates. Individual anatomy is used only to scale the coordinates based on the location of some internal guide points. While on conventional MR imaging the thalamic nuclei are indistinguishable, recently it has become possible to identify individual thalamic nuclei using different connectivity profiles, as defined by MR diffusion tractography. METHODOLOGY AND PRINCIPAL FINDINGS: Here we investigated the inter-individual variation of the location of target nuclei for thalamotomy: the putative ventralis oralis posterior (Vop and the ventral intermedius (Vim nucleus as defined by probabilistic tractography. We showed that the mean inter-individual distance of the peak Vop location is 7.33 mm and 7.42 mm for Vim. The mean overlap between individual Vop nuclei was 40.2% and it was 31.8% for Vim nuclei. As a proof of concept, we also present a patient who underwent Vop thalamotomy for untreatable tremor caused by traumatic brain injury and another patient who underwent Vim thalamotomy for essential tremor. The probabilistic tractography indicated that the successful tremor control was achieved with lesions in the Vop and Vim respectively. CONCLUSIONS: Our data call attention to the need for a better appreciation of the individual anatomy when planning stereotactic functional neurosurgery.

  20. Identification of novel androgen receptor target genes in prostate cancer

    Directory of Open Access Journals (Sweden)

    Gerald William L

    2007-06-01

    Full Text Available Abstract Background The androgen receptor (AR plays critical roles in both androgen-dependent and castrate-resistant prostate cancer (PCa. However, little is known about AR target genes that mediate the receptor's roles in disease progression. Results Using Chromatin Immunoprecipitation (ChIP Display, we discovered 19 novel loci occupied by the AR in castrate resistant C4-2B PCa cells. Only four of the 19 AR-occupied regions were within 10-kb 5'-flanking regulatory sequences. Three were located up to 4-kb 3' of the nearest gene, eight were intragenic and four were in gene deserts. Whereas the AR occupied the same loci in C4-2B (castrate resistant and LNCaP (androgen-dependent PCa cells, differences between the two cell lines were observed in the response of nearby genes to androgens. Among the genes strongly stimulated by DHT in C4-2B cells – D-dopachrome tautomerase (DDT, Protein kinase C delta (PRKCD, Glutathione S- transferase theta 2 (GSTT2, Transient receptor potential cation channel subfamily V member 3 (TRPV3, and Pyrroline-5-carboxylate reductase 1 (PYCR1 – most were less strongly or hardly stimulated in LNCaP cells. Another AR target gene, ornithine aminotransferase (OAT, was AR-stimulated in a ligand-independent manner, since it was repressed by AR siRNA knockdown, but not stimulated by DHT. We also present evidence for in vivo AR-mediated regulation of several genes identified by ChIP Display. For example, PRKCD and PYCR1, which may contribute to PCa cell growth and survival, are expressed in PCa biopsies from primary tumors before and after ablation and in metastatic lesions in a manner consistent with AR-mediated stimulation. Conclusion AR genomic occupancy is similar between LNCaP and C4-2B cells and is not biased towards 5' gene flanking sequences. The AR transcriptionally regulates less than half the genes nearby AR-occupied regions, usually but not always, in a ligand-dependent manner. Most are stimulated and a few are

  1. Learning representations for improved target identification, scene classification, and information fusion

    Science.gov (United States)

    Flenner, Arjuna; Culp, Michael; McGee, Ryan; Flenner, Jennifer; Garcia-Cardona, Cristina

    2015-05-01

    Object representation is fundamental to Automated Target Recognition (ATR). Many ATR approaches choose a basis, such as a wavelet or Fourier basis, to represent the target. Recently, advancements in Image and Signal processing have shown that object recognition can be improved if, rather than a assuming a basis, a database of training examples is used to learn a representation. We discuss learning representations using Non-parametric Bayesian topic models, and demonstrate how to integrate information from other sources to improve ATR. We apply the method to EO and IR information integration for vehicle target identification and show that the learned representation of the joint EO and IR information improves target identification by 4%. Furthermore, we demonstrate that we can integrate text and imagery data to direct the representation for mission specific tasks and improve performance by 8%. Finally, we illustrate integrating graphical models into representation learning to improve performance by 2%.

  2. Identification of targetable FGFR gene fusions in diverse cancers.

    Science.gov (United States)

    Wu, Yi-Mi; Su, Fengyun; Kalyana-Sundaram, Shanker; Khazanov, Nickolay; Ateeq, Bushra; Cao, Xuhong; Lonigro, Robert J; Vats, Pankaj; Wang, Rui; Lin, Su-Fang; Cheng, Ann-Joy; Kunju, Lakshmi P; Siddiqui, Javed; Tomlins, Scott A; Wyngaard, Peter; Sadis, Seth; Roychowdhury, Sameek; Hussain, Maha H; Feng, Felix Y; Zalupski, Mark M; Talpaz, Moshe; Pienta, Kenneth J; Rhodes, Daniel R; Robinson, Dan R; Chinnaiyan, Arul M

    2013-06-01

    Through a prospective clinical sequencing program for advanced cancers, four index cases were identified which harbor gene rearrangements of FGFR2, including patients with cholangiocarcinoma, breast cancer, and prostate cancer. After extending our assessment of FGFR rearrangements across multiple tumor cohorts, we identified additional FGFR fusions with intact kinase domains in lung squamous cell cancer, bladder cancer, thyroid cancer, oral cancer, glioblastoma, and head and neck squamous cell cancer. All FGFR fusion partners tested exhibit oligomerization capability, suggesting a shared mode of kinase activation. Overexpression of FGFR fusion proteins induced cell proliferation. Two bladder cancer cell lines that harbor FGFR3 fusion proteins exhibited enhanced susceptibility to pharmacologic inhibition in vitro and in vivo. Because of the combinatorial possibilities of FGFR family fusion to a variety of oligomerization partners, clinical sequencing efforts, which incorporate transcriptome analysis for gene fusions, are poised to identify rare, targetable FGFR fusions across diverse cancer types.

  3. Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish

    Directory of Open Access Journals (Sweden)

    Xingang Wang

    2013-09-01

    Hedgehog (Hh signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot, consistent with their being direct targets of Gli2a.

  4. Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish.

    Science.gov (United States)

    Wang, Xingang; Zhao, Zhonghua; Muller, Julius; Iyu, Audrey; Khng, Alexis Jiaying; Guccione, Ernesto; Ruan, Yijun; Ingham, Philip W

    2013-01-01

    Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performed chromatin immunoprecipitation sequencing (ChIP-seq) of whole embryo extracts. Samples were significantly enriched for 192 genomic regions, some of which are associated with four known Hh target genes, ptch1, ptch2, gli1 and olig2. Sequence analysis of these regions reveals a high level of conservation of Gli-binding sites from fish to mammals in some, but not all, cases. Expression analysis of other transcription units that are closely associated with peaks identified several putative targets not previously implicated as Hh targets, including myl10, hnmt, lrp4, efemp2, fras1, quo, and lamc1. Each of these genes shows loss of, or reduced expression in, embryos homozygous for an antimorphic allele of gli2a, you-too (yot), consistent with their being direct targets of Gli2a.

  5. Nonsearching Doppler parameter and velocity estimation method for synthetic aperture radar ground moving target imaging

    Science.gov (United States)

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

    2016-07-01

    For synthetic aperture radar (SAR), ground moving target (GMT) imaging necessitates the compensation of the additional azimuth modulation contributed by the unknown movement of the GMT. That is to say, it is necessary to estimate the Doppler parameters of the GMT without a priori knowledge of the GMT's motion parameters. This paper presents a Doppler parameter and velocity estimation method to refocus the GMT from its smeared response in SAR image. The main idea of this method is that an azimuth reference function is constructed to do the correlation integral with the azimuth signal of the GMT. And in general, the Doppler parameters of the presumed azimuth reference function are different from those of the GMT's azimuth signal since the velocity parameters of the GMT are unknown. Therefore, the correlation operation referred to here is actually mismatched, and the processing result of is shifted and defocused. The shifted and defocused result is utilized to get the real Doppler parameters and the velocity parameters of the GMT. One advantage of this method is that it is a nonsearching method. Another advantage is that both the Doppler centroid and the Doppler frequency rate of the GMT can be simultaneously estimated according to the relationships between the Doppler parameters and the smeared response of the GMT. In addition, the velocity of the GMT can also be obtained based on the estimated Doppler parameters. Numerical simulations and experimental data processing verify the validity of the method proposed.

  6. Targeted inactivation and identification of targets of the Gli2a transcription factor in the zebrafish

    OpenAIRE

    2013-01-01

    Summary Hedgehog (Hh) signaling is mediated by the Gli transcription factors and, in the zebrafish, plays an important role in patterning both the neural tube and myotome. Using a null allele of the gli2a gene induced by targeted mutagenesis, we show that Gli2a is completely dispensable in the fish but acts redundantly with Gli1 to regulate expression of known Hh targets, such as ptch2, prdm1a and eng2a, in the myotome and neural tube. To identify novel targets of Hh signaling, we performe...

  7. Advances in identification and validation of protein targets of natural products without chemical modification.

    Science.gov (United States)

    Chang, J; Kim, Y; Kwon, H J

    2016-05-04

    Covering: up to February 2016Identification of the target proteins of natural products is pivotal to understanding the mechanisms of action to develop natural products for use as molecular probes and potential therapeutic drugs. Affinity chromatography of immobilized natural products has been conventionally used to identify target proteins, and has yielded good results. However, this method has limitations, in that labeling or tagging for immobilization and affinity purification often result in reduced or altered activity of the natural product. New strategies have recently been developed and applied to identify the target proteins of natural products and synthetic small molecules without chemical modification of the natural product. These direct and indirect methods for target identification of label-free natural products include drug affinity responsive target stability (DARTS), stability of proteins from rates of oxidation (SPROX), cellular thermal shift assay (CETSA), thermal proteome profiling (TPP), and bioinformatics-based analysis of connectivity. This review focuses on and reports case studies of the latest advances in target protein identification methods for label-free natural products. The integration of newly developed technologies will provide new insights and highlight the value of natural products for use as biological probes and new drug candidates.

  8. Identification of Ski as a target for Aurora A kinase.

    Science.gov (United States)

    Mosquera, Jocelyn; Armisen, Ricardo; Zhao, Hongling; Rojas, Diego A; Maldonado, Edio; Tapia, Julio C; Colombo, Alicia; Hayman, Michael J; Marcelain, Katherine

    2011-06-10

    Ski is a negative regulator of the transforming growth factor-β and other signalling pathways. The absence of SKI in mouse fibroblasts leads to chromosome segregation defects and genomic instability, suggesting a role for Ski during mitosis. At this stage, Ski is phosphorylated but to date little is known about the kinases involved in this process. Here, we show that Aurora A kinase is able to phosphorylate Ski in vitro. In vivo, Aurora A and Ski co-localized at the centrosomes and co-immunoprecipitated. Conversely, a C-terminal truncation mutant of Ski (SkiΔ491-728) lacking a coiled-coil domain, displayed decreased centrosomal localization. This mutant no longer co-immunoprecipitated with Aurora-A in vivo, but was still phosphorylated in vitro, indicating that the Ski-Aurora A interaction takes place at the centrosomes. These data identify Ski as a novel target of Aurora A and contribute to an understanding of the role of these proteins in the mitotic process.

  9. Identification of the platelet ADP receptor targeted by antithrombotic drugs.

    Science.gov (United States)

    Hollopeter, G; Jantzen, H M; Vincent, D; Li, G; England, L; Ramakrishnan, V; Yang, R B; Nurden, P; Nurden, A; Julius, D; Conley, P B

    2001-01-11

    Platelets have a crucial role in the maintenance of normal haemostasis, and perturbations of this system can lead to pathological thrombus formation and vascular occlusion, resulting in stroke, myocardial infarction and unstable angina. ADP released from damaged vessels and red blood cells induces platelet aggregation through activation of the integrin GPIIb-IIIa and subsequent binding of fibrinogen. ADP is also secreted from platelets on activation, providing positive feedback that potentiates the actions of many platelet activators. ADP mediates platelet aggregation through its action on two G-protein-coupled receptor subtypes. The P2Y1 receptor couples to Gq and mobilizes intracellular calcium ions to mediate platelet shape change and aggregation. The second ADP receptor required for aggregation (variously called P2Y(ADP), P2Y(AC), P2Ycyc or P2T(AC)) is coupled to the inhibition of adenylyl cyclase through Gi. The molecular identity of the Gi-linked receptor is still elusive, even though it is the target of efficacious antithrombotic agents, such as ticlopidine and clopidogrel and AR-C66096 (ref. 9). Here we describe the cloning of this receptor, designated P2Y12, and provide evidence that a patient with a bleeding disorder has a defect in this gene. Cloning of the P2Y12 receptor should facilitate the development of better antiplatelet agents to treat cardiovascular diseases.

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

    Science.gov (United States)

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

    2006-04-01

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

  11. Employing machine learning for reliable miRNA target identification in plants

    Directory of Open Access Journals (Sweden)

    Jha Ashwani

    2011-12-01

    Full Text Available Abstract Background miRNAs are ~21 nucleotide long small noncoding RNA molecules, formed endogenously in most of the eukaryotes, which mainly control their target genes post transcriptionally by interacting and silencing them. While a lot of tools has been developed for animal miRNA target system, plant miRNA target identification system has witnessed limited development. Most of them have been centered around exact complementarity match. Very few of them considered other factors like multiple target sites and role of flanking regions. Result In the present work, a Support Vector Regression (SVR approach has been implemented for plant miRNA target identification, utilizing position specific dinucleotide density variation information around the target sites, to yield highly reliable result. It has been named as p-TAREF (plant-Target Refiner. Performance comparison for p-TAREF was done with other prediction tools for plants with utmost rigor and where p-TAREF was found better performing in several aspects. Further, p-TAREF was run over the experimentally validated miRNA targets from species like Arabidopsis, Medicago, Rice and Tomato, and detected them accurately, suggesting gross usability of p-TAREF for plant species. Using p-TAREF, target identification was done for the complete Rice transcriptome, supported by expression and degradome based data. miR156 was found as an important component of the Rice regulatory system, where control of genes associated with growth and transcription looked predominant. The entire methodology has been implemented in a multi-threaded parallel architecture in Java, to enable fast processing for web-server version as well as standalone version. This also makes it to run even on a simple desktop computer in concurrent mode. It also provides a facility to gather experimental support for predictions made, through on the spot expression data analysis, in its web-server version. Conclusion A machine learning

  12. A conceptual framework for the identification of candidate drugs and drug targets in acute promyelocytic leukemia

    DEFF Research Database (Denmark)

    Marstrand, T T; Borup, R; Willer, A

    2010-01-01

    regulation, and (ii) the identification of candidate drugs and drug targets for therapeutic interventions. Significantly, our study provides a conceptual framework that can be applied to any subtype of AML and cancer in general to uncover novel information from published microarray data sets at low cost...

  13. Identification of air and sea-surface targets with a laser range profiler

    NARCIS (Netherlands)

    Heuvel, J.C. van den; Schoemaker, R.M.; Schleijpen, H.M.A.

    2009-01-01

    Current coastal operations have to deal with threats at short range in complex environments with both neutral and hostile targets. There is a need for fast identification, which is possible with a laser range profiler. A number of field trials have been conducted to validate the concept of

  14. Identification of New Drug Targets in Multi-Drug Resistant Bacterial Infections

    Science.gov (United States)

    2012-10-01

    COVERED 26 September 2011 25 September 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Identification of New Drug Targets in Multi-Drug Resistant...will be necessary for the fragment based screening and subsequent design of new drug lead compounds. To accompany and validate the structural studies

  15. The Asteroid Identification Problem. II. Target Plane Confidence Boundaries

    Science.gov (United States)

    Milani, Andrea; Valsecchi, Giovanni B.

    1999-08-01

    The nominal orbit solution for an asteroid/comet resulting from a least squares fit to astrometric observations is surrounded by a region containing solutions equally compatible with the data, the confidence region. If the observed arc is not too short, and for an epoch close to the observations, the confidence region in the six-dimensional space of orbital elements is well approximated by an ellipsoid. This uncertainty of the orbital elements maps to a position uncertainty at close approach, which can be represented on a Modified Target Plane (MTP), a modification of the one used by Öpik. The MTP is orthogonal to the geocentric velocity at the closest approach point along the nominal orbit. In the linear approximation, the confidence ellipsoids are mapped on the MTP into concentric ellipses, computed by solving the variational equation. For an object observed at only one opposition, however, if the close approach is expected after many revolutions, the ellipses on the MTP become extremely elongated, therefore the linear approximation may fail, and the confidence boundaries on the MTP, by definition the nonlinear images of the confidence ellipsoids, may not be well approximated by the ellipses. In theory the Monte Carlo method by Muinonen and Bowell (1993, Icarus104, 255-279) can be used to compute the nonlinear confidence boundaries, but in practice the computational load is very heavy. We propose a new method to compute semilinear confidence boundaries on the MTP, based on the theory developed by Milani (1999, Icarus137, 269-292) to efficiently compute confidence boundaries for predicted observations. This method is a reasonable compromise between reliability and computational load, and can be used for real time risk assessment. These arguments can be applied to any small body approaching any planet, but in the case of a potentially hazardous object (PHO), either an asteroid or a comet whose orbit comes very close to that of the Earth, the application is most

  16. Analysis of Geosynchronous Satellite-air Bistatic SAR Clutter Characteristics from the Point of View of Ground Moving Target Indication

    Directory of Open Access Journals (Sweden)

    Zhang Dan-dan

    2013-09-01

    Full Text Available Under the geometry of geosynchronous satellite-air bistatic SAR where the geosynchronous satellite is the transmitter and aerostat is the receiver, in order to suppress clutter and detect slowly moving target using Space Time Adaptive Processing (STAP, it is necessary to analyze the clutter characteristics. From the point of view of ground moving target indication, the theory model of the clutter characteristics under the geometry of geosynchronous satellite-space bistatic SAR is analyzed and established in this paper; especially, the range-dependence characteristics of the angle-Doppler curve of the clutter is analyzed. Finally, the simulation verifies correctness of the analysis. The theory model and the conclusion in this paper indicates the clutter characteristics of the new geosynchronous satellite-air bistatic SAR mode, and provide theory basis for the selection and research of ground moving target indication method under this mode.

  17. Road-Aided Ground Slowly Moving Target 2D Motion Estimation for Single-Channel Synthetic Aperture Radar.

    Science.gov (United States)

    Wang, Zhirui; Xu, Jia; Huang, Zuzhen; Zhang, Xudong; Xia, Xiang-Gen; Long, Teng; Bao, Qian

    2016-03-16

    To detect and estimate ground slowly moving targets in airborne single-channel synthetic aperture radar (SAR), a road-aided ground moving target indication (GMTI) algorithm is proposed in this paper. First, the road area is extracted from a focused SAR image based on radar vision. Second, after stationary clutter suppression in the range-Doppler domain, a moving target is detected and located in the image domain via the watershed method. The target's position on the road as well as its radial velocity can be determined according to the target's offset distance and traffic rules. Furthermore, the target's azimuth velocity is estimated based on the road slope obtained via polynomial fitting. Compared with the traditional algorithms, the proposed method can effectively cope with slowly moving targets partly submerged in a stationary clutter spectrum. In addition, the proposed method can be easily extended to a multi-channel system to further improve the performance of clutter suppression and motion estimation. Finally, the results of numerical experiments are provided to demonstrate the effectiveness of the proposed algorithm.

  18. A Modular Probe Strategy for Drug Localization, Target Identification and Target Occupancy Measurement on Single Cell Level.

    Science.gov (United States)

    Rutkowska, Anna; Thomson, Douglas W; Vappiani, Johanna; Werner, Thilo; Mueller, Katrin M; Dittus, Lars; Krause, Jana; Muelbaier, Marcel; Bergamini, Giovanna; Bantscheff, Marcus

    2016-09-16

    Late stage failures of candidate drug molecules are frequently caused by off-target effects or inefficient target engagement in vivo. In order to address these fundamental challenges in drug discovery, we developed a modular probe strategy based on bioorthogonal chemistry that enables the attachment of multiple reporters to the same probe in cell extracts and live cells. In a systematic evaluation, we identified the inverse electron demand Diels-Alder reaction between trans-cyclooctene labeled probe molecules and tetrazine-tagged reporters to be the most efficient bioorthogonal reaction for this strategy. Bioorthogonal biotinylation of the probe allows the identification of drug targets in a chemoproteomics competition binding assay using quantitative mass spectrometry. Attachment of a fluorescent reporter enables monitoring of spatial localization of probes as well as drug-target colocalization studies. Finally, direct target occupancy of unlabeled drugs can be determined at single cell resolution by competitive binding with fluorescently labeled probe molecules. The feasibility of the modular probe strategy is demonstrated with noncovalent PARP inhibitors.

  19. On-orbit real-time robust cooperative target identification in complex background

    Institute of Scientific and Technical Information of China (English)

    Wen Zhuoman; Wang Yanjie; Arjan Kuijper; Di Nan; Luo Jun; Zhang Lei; Jin Minghe

    2015-01-01

    Cooperative target identification is the prerequisite for the relative position and orienta-tion measurement between the space robot arm and the to-be-arrested object. We propose an on-orbit real-time robust algorithm for cooperative target identification in complex background using the features of circle and lines. It first extracts only the interested edges in the target image using an adaptive threshold and refines them to about single-pixel-width with improved non-maximum sup-pression. Adapting a novel tracking approach, edge segments changing smoothly in tangential directions are obtained. With a small amount of calculation, large numbers of invalid edges are removed. From the few remained edges, valid circular arcs are extracted and reassembled to obtain circles according to a reliable criterion. Finally, the target is identified if there are certain numbers of straight lines whose relative positions with the circle match the known target pattern. Experiments demonstrate that the proposed algorithm accurately identifies the cooperative target within the range of 0.3–1.5 m under complex background at the speed of 8 frames per second, regardless of lighting condition and target attitude. The proposed algorithm is very suitable for real-time visual measurement of space robot arm because of its robustness and small memory requirement.

  20. On-orbit real-time robust cooperative target identification in complex background

    Directory of Open Access Journals (Sweden)

    Wen Zhuoman

    2015-10-01

    Full Text Available Cooperative target identification is the prerequisite for the relative position and orientation measurement between the space robot arm and the to-be-arrested object. We propose an on-orbit real-time robust algorithm for cooperative target identification in complex background using the features of circle and lines. It first extracts only the interested edges in the target image using an adaptive threshold and refines them to about single-pixel-width with improved non-maximum suppression. Adapting a novel tracking approach, edge segments changing smoothly in tangential directions are obtained. With a small amount of calculation, large numbers of invalid edges are removed. From the few remained edges, valid circular arcs are extracted and reassembled to obtain circles according to a reliable criterion. Finally, the target is identified if there are certain numbers of straight lines whose relative positions with the circle match the known target pattern. Experiments demonstrate that the proposed algorithm accurately identifies the cooperative target within the range of 0.3–1.5 m under complex background at the speed of 8 frames per second, regardless of lighting condition and target attitude. The proposed algorithm is very suitable for real-time visual measurement of space robot arm because of its robustness and small memory requirement.

  1. Identification of a Potential Target of Capsaicin by Computational Target Fishing

    Directory of Open Access Journals (Sweden)

    Xuan-yi Ye

    2015-01-01

    Full Text Available Capsaicin, the component responsible for the pungency of chili peppers, shows beneficial effects in many diseases, although the underlying mechanisms remain unclear. In the present study, the potential targets of capsaicin were predicted using PharmMapper and confirmed via chemical-protein interactome (CPI and molecular docking. Carbonic anhydrase 2 was identified as the main disease-related target, with the pharmacophore model matching well with the molecular features of capsaicin. The relation was confirmed by CPI and molecular docking and supported by previous research showing that capsaicin is a potent inhibitor of carbonic anhydrase isoenzymes. The present study provides a basis for understanding the mechanisms of action of capsaicin or those of other natural compounds.

  2. Target identification and navigation performance modeling of a passive millimeter wave imager.

    Science.gov (United States)

    Jacobs, Eddie L; Furxhi, Orges

    2010-07-01

    Human task performance using a passive interferometric millimeter wave imaging sensor is modeled using a task performance modeling approach developed by the U.S. Army Night Vision and Electronic Sensors Directorate. The techniques used are illustrated for an imaging system composed of an interferometric antenna array, optical upconversion, and image formation using a shortwave infrared focal plane array. Two tasks, target identification and pilotage, are modeled. The effects of sparse antenna arrays on task performance are considered. Applications of this model include system trade studies for concealed weapon identification, navigation in fog, and brownout conditions.

  3. The Effects of Highlighting, Validity, and Feature Type on Air-to-Ground Target Acquisition Performance.

    Science.gov (United States)

    2007-11-02

    cultura I taget Target type Validity X target X leadin interaction on initial response time (highlighted trials) WRONG HIGHLIGHTING ÖU - M ea...natural - leadin cultural ndurd cultura taget I taget Target type Figure 3.10: Validity X lead-in X Target interaction Confirmation time A

  4. Identification of control targets in Boolean molecular network models via computational algebra.

    Science.gov (United States)

    Murrugarra, David; Veliz-Cuba, Alan; Aguilar, Boris; Laubenbacher, Reinhard

    2016-09-23

    Many problems in biomedicine and other areas of the life sciences can be characterized as control problems, with the goal of finding strategies to change a disease or otherwise undesirable state of a biological system into another, more desirable, state through an intervention, such as a drug or other therapeutic treatment. The identification of such strategies is typically based on a mathematical model of the process to be altered through targeted control inputs. This paper focuses on processes at the molecular level that determine the state of an individual cell, involving signaling or gene regulation. The mathematical model type considered is that of Boolean networks. The potential control targets can be represented by a set of nodes and edges that can be manipulated to produce a desired effect on the system. This paper presents a method for the identification of potential intervention targets in Boolean molecular network models using algebraic techniques. The approach exploits an algebraic representation of Boolean networks to encode the control candidates in the network wiring diagram as the solutions of a system of polynomials equations, and then uses computational algebra techniques to find such controllers. The control methods in this paper are validated through the identification of combinatorial interventions in the signaling pathways of previously reported control targets in two well studied systems, a p53-mdm2 network and a blood T cell lymphocyte granular leukemia survival signaling network. Supplementary data is available online and our code in Macaulay2 and Matlab are available via http://www.ms.uky.edu/~dmu228/ControlAlg . This paper presents a novel method for the identification of intervention targets in Boolean network models. The results in this paper show that the proposed methods are useful and efficient for moderately large networks.

  5. Forensic identification science evidence since Daubert: Part II--judicial reasoning in decisions to exclude forensic identification evidence on grounds of reliability.

    Science.gov (United States)

    Page, Mark; Taylor, Jane; Blenkin, Matt

    2011-07-01

    Many studies regarding the legal status of forensic science have relied on the U.S. Supreme Court's mandate in Daubert v. Merrell Dow Pharmaceuticals Inc., and its progeny in order to make subsequent recommendations or rebuttals. This paper focuses on a more pragmatic approach to analyzing forensic science's immediate deficiencies by considering a qualitative analysis of actual judicial reasoning where forensic identification evidence has been excluded on reliability grounds since the Daubert precedent. Reliance on general acceptance is becoming insufficient as proof of the admissibility of forensic evidence. The citation of unfounded statistics, error rates and certainties, a failure to document the analytical process or follow standardized procedures, and the existence of observe bias represent some of the concerns that have lead to the exclusion or limitation of forensic identification evidence. Analysis of these reasons may serve to refocus forensic practitioners' testimony, resources, and research toward rectifying shortfalls in these areas.

  6. Development of a vision-based ground target detection and tracking system for a small unmanned helicopter

    Institute of Scientific and Technical Information of China (English)

    LIN Feng; LUM Kai-Yew; CHEN Ben M.; LEE Tong H

    2009-01-01

    It is undoubted that the latest trend in the unmanned aerial vehicles (UAVs) community is towards visionbased unmanned small-scale helicopter,utilizing the maneuvering capabilities of the helicopter and the rich information of visual sensors,in order to arrive at a versatile platform for a variety of applications such as navigation,surveillance,tracking,etc.In this paper,we present the development of a visionbased ground target detection and tracking system for a small UAV helicopter.More specifically,we propose a real-time vision algorithm,based on moment invariants and two-stage pattern recognition,to achieve automatic ground target detection.In the proposed algorithm,the key geometry features of the target are extracted to detect and identify the target.Simultaneously,a Kalman filter is used to estimate and predict the position of the target,referred to as dynamic features,based on its motion model.These dynamic features are then combined with geometry features to identify the target in the second-stage of pattern recognition,when geometry features of the target change significantly due to noise and disturbance in the environment.Once the target is identified,an automatic control scheme is utilized to control the pan/tilt visual mechanism mounted on the helicopter such that the identified target is to be tracked at the center of the captured images.Experimental results based on images captured by the small-scale unmanned helicopter,SheLion,in actual flight tests demonstrate the effectiveness and robustness of the overall system.

  7. New approaches for the identification of drug targets in protozoan parasites.

    Science.gov (United States)

    Müller, Joachim; Hemphill, Andrew

    2013-01-01

    Antiparasitic chemotherapy is an important issue for drug development. Traditionally, novel compounds with antiprotozoan activities have been identified by screening of compound libraries in high-throughput systems. More recently developed approaches employ target-based drug design supported by genomics and proteomics of protozoan parasites. In this chapter, the drug targets in protozoan parasites are reviewed. The gene-expression machinery has been among the first targets for antiparasitic drugs and is still under investigation as a target for novel compounds. Other targets include cytoskeletal proteins, proteins involved in intracellular signaling, membranes, and enzymes participating in intermediary metabolism. In apicomplexan parasites, the apicoplast is a suitable target for established and novel drugs. Some drugs act on multiple subcellular targets. Drugs with nitro groups generate free radicals under anaerobic growth conditions, and drugs with peroxide groups generate radicals under aerobic growth conditions, both affecting multiple cellular pathways. Mefloquine and thiazolides are presented as examples for antiprotozoan compounds with multiple (side) effects. The classic approach of drug discovery employing high-throughput physiological screenings followed by identification of drug targets has yielded the mainstream of current antiprotozoal drugs. Target-based drug design supported by genomics and proteomics of protozoan parasites has not produced any antiparasitic drug so far. The reason for this is discussed and a synthesis of both methods is proposed.

  8. Identification of novel targets for miR-29a using miRNA proteomics.

    Directory of Open Access Journals (Sweden)

    Rhishikesh Bargaje

    Full Text Available MicroRNAs (miRNAs are short regulatory RNA molecules that interfere with the expression of target mRNA by binding to complementary sequences. Currently, the most common method for identification of targets of miRNAs is computational prediction based on free energy change calculations, target site accessibility and conservation. Such algorithms predict hundreds of targets for each miRNA, necessitating tedious experimentation to identify the few functional targets. Here we explore the utility of miRNA-proteomics as an approach to identifying functional miRNA targets. We used Stable Isotope Labeling by amino acids in cell culture (SILAC based proteomics to detect differences in protein expression induced by the over-expression of miR-34a and miR-29a. Over-expression of miR-29a, a miRNA expressed in the brain and in cells of the blood lineage, resulted in the differential expression of a set of proteins. Gene Ontology based classification showed that a significant sub-set of these targets, including Voltage Dependent Anion Channel 1 and 2 (VDAC1 and VDAC2 and ATP synthetase, were mitochondrial proteins involved in apoptosis. Using reporter assays, we established that miR-29a targets the 3' Untranslated Regions (3' UTR of VDAC1 and VDAC2. However, due to the limited number of proteins identified using this approach and the inability to differentiate between primary and secondary effects we conclude that miRNA-proteomics is of limited utility as a high-throughput alternative for sensitive and unbiased miRNA target identification. However, this approach was valuable for rapid assessment of the impact of the miRNAs on the cellular proteome and its biological role in apoptosis.

  9. Hardware in the Loop Implementation of Adaptive Vision Based Guidance Law for Ground Target Tracking

    Science.gov (United States)

    2008-12-01

    53 Figure 31. PTU -D300 from Directed Perceptions...54 Figure 32. xPC Driver Model for the PTU -D300 .................................................. 55 Figure 33. Ground... PTU -D300...................................................... 55 Table 2. Summary of S-Functions

  10. Fusion of Imperfect Information in the Unified Framework of Random Sets Theory: Application to Target Identification

    Science.gov (United States)

    2007-11-01

    Informatique WGZ Anne-Laure Jousselme Éloi Bossé DRDC Valcartier Defence R&D Canada – Valcartier Technical Report DRDC Valcartier TR 2003-319 November 2007...Fusion of imperfect information in the unified framework of random sets theory Application to target identification Mihai Cristian Florea Informatique ...Cell CFB Esquimalt P.O. Box 17000 Stn Forces Victoria, British Columbia, V9A 7N2 Attn: Commanding Officer 1 M. C. Florea (author) Informatique WGZ inc

  11. Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary Gland

    Science.gov (United States)

    2014-11-01

    AD_________________ Award Number: W81XWH-11-1-0152 TITLE: Vitamin D Pathway Status and the Identification of Target Genes in the Mouse Mammary...Final Report 3. DATES COVERED 1 Jan 2011 – 31 Nov 2014 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Vitamin D Pathway Status and the...SUPPLEMENTARY NOTES 14. ABSTRACT Mammary gland samples were isolated from wild type, vitamin D receptor knockout (VDRKO) and 1alphahydroxylase

  12. Reduced-order model for underwater target identification using proper orthogonal decomposition

    Science.gov (United States)

    Ramesh, Sai Sudha; Lim, Kian Meng

    2017-03-01

    Research on underwater acoustics has seen major development over the past decade due to its widespread applications in domains such as underwater communication/navigation (SONAR), seismic exploration and oceanography. In particular, acoustic signatures from partially or fully buried targets can be used in the identification of buried mines for mine counter measures (MCM). Although there exist several techniques to identify target properties based on SONAR images and acoustic signatures, these methods first employ a feature extraction method to represent the dominant characteristics of a data set, followed by the use of an appropriate classifier based on neural networks or the relevance vector machine. The aim of the present study is to demonstrate the applications of proper orthogonal decomposition (POD) technique in capturing dominant features of a set of scattered pressure signals, and subsequent use of the POD modes and coefficients in the identification of partially buried underwater target parameters such as its location, size and material density. Several numerical examples are presented to demonstrate the performance of the system identification method based on POD. Although the present study is based on 2D acoustic model, the method can be easily extended to 3D models and thereby enables cost-effective representations of large-scale data.

  13. Ground Clutter Reduction from GPR Data for Identification of Shallowly Buried Landmines

    Science.gov (United States)

    Nishimoto, Masahiko; Jandieri, Vakhtang

    A method for reducing ground clutter contribution from ground penetrating radar (GPR) data is proposed for discrimination of landmines located in shallow depth. The algorithm of this method is based on the Matching Pursuit (MP) that is a technique for non-orthogonal signal decomposition using dictionary of functions. As the dictionary of function, a wave-based dictionary constructed by taking account of scattering mechanisms of electromagnetic (EM) wave by rough surfaces is employed. Through numerical simulations, performance of ground clutter reduction is evaluated. The results show that the proposed method has good performance and is effective for GPR data preprocessing for discrimination of shallowly buried landmines.

  14. Molecular species identification of Central European ground beetles (Coleoptera: Carabidae using nuclear rDNA expansion segments and DNA barcodes

    Directory of Open Access Journals (Sweden)

    Raupach Michael J

    2010-09-01

    Full Text Available Abstract Background The identification of vast numbers of unknown organisms using DNA sequences becomes more and more important in ecological and biodiversity studies. In this context, a fragment of the mitochondrial cytochrome c oxidase I (COI gene has been proposed as standard DNA barcoding marker for the identification of organisms. Limitations of the COI barcoding approach can arise from its single-locus identification system, the effect of introgression events, incomplete lineage sorting, numts, heteroplasmy and maternal inheritance of intracellular endosymbionts. Consequently, the analysis of a supplementary nuclear marker system could be advantageous. Results We tested the effectiveness of the COI barcoding region and of three nuclear ribosomal expansion segments in discriminating ground beetles of Central Europe, a diverse and well-studied invertebrate taxon. As nuclear markers we determined the 18S rDNA: V4, 18S rDNA: V7 and 28S rDNA: D3 expansion segments for 344 specimens of 75 species. Seventy-three species (97% of the analysed species could be accurately identified using COI, while the combined approach of all three nuclear markers provided resolution among 71 (95% of the studied Carabidae. Conclusion Our results confirm that the analysed nuclear ribosomal expansion segments in combination constitute a valuable and efficient supplement for classical DNA barcoding to avoid potential pitfalls when only mitochondrial data are being used. We also demonstrate the high potential of COI barcodes for the identification of even closely related carabid species.

  15. Strontium isotopic identification of water-rock interaction and ground water mixing.

    Science.gov (United States)

    Frost, Carol D; Toner, Rachel N

    2004-01-01

    87Sr/86Sr ratios of ground waters in the Bighorn and Laramie basins' carbonate and carbonate-cemented aquifer systems, Wyoming, United States, reflect the distinctive strontium isotope signatures of the minerals in their respective aquifers. Well water samples from the Madison Aquifer (Bighorn Basin) have strontium isotopic ratios that match their carbonate host rocks. Casper Aquifer ground waters (Laramie Basin) have strontium isotopic ratios that differ from the bulk host rock; however, stepwise leaching of Casper Sandstone indicates that most of the strontium in Casper Aquifer ground waters is acquired from preferential dissolution of carbonate cement. Strontium isotope data from both Bighorn and Laramie basins, along with dye tracing experiments in the Bighorn Basin and tritium data from the Laramie Basin, suggest that waters in carbonate or carbonate-cemented aquifers acquire their strontium isotope composition very quickly--on the order of decades. Strontium isotopes were also used successfully to verify previously identified mixed Redbeds-Casper ground waters in the Laramie Basin. The strontium isotopic compositions of ground waters near Precambrian outcrops also suggest previously unrecognized mixing between Casper and Precambrian aquifers. These results demonstrate the utility of strontium isotopic ratio data in identifying ground water sources and aquifer interactions.

  16. Identification of conserved microRNAs and their target genes in tomato (Lycopersicon esculentum).

    Science.gov (United States)

    Yin, Zujun; Li, Chunhe; Han, Xiulan; Shen, Fafu

    2008-05-15

    MicroRNAs (miRNAs) are a class of non-coding RNAs that have important gene regulation roles in various organisms. To date, a total of 1279 plant miRNAs have been deposited in the miRNA miRBase database (Release 10.1). Many of them are conserved during the evolution of land plants suggesting that the well-conserved miRNAs may also retain homologous target interactions. Recently, little is known about the experimental or computational identification of conserved miRNAs and their target genes in tomato. Here, using a computational homology search approach, 21 conserved miRNAs were detected in the Expressed Sequence Tags (EST) and Genomic Survey Sequence (GSS) databases. Following this, 57 potential target genes were predicted by searching the mRNA database. Most of the target mRNAs appeared to be involved in plant growth and development. Our findings verified that the well-conserved tomato miRNAs have retained homologous target interactions amongst divergent plant species. Some miRNAs express diverse combinations in different cell types and have been shown to regulate cell-specific target genes coordinately. We believe that the targeting propensity for genes in different biological processes can be explained largely by their protein connectivity.

  17. Drug target identification using network analysis: Taking active components in Sini decoction as an example.

    Science.gov (United States)

    Chen, Si; Jiang, Hailong; Cao, Yan; Wang, Yun; Hu, Ziheng; Zhu, Zhenyu; Chai, Yifeng

    2016-04-20

    Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.

  18. Drug target identification using network analysis: Taking active components in Sini decoction as an example

    Science.gov (United States)

    Chen, Si; Jiang, Hailong; Cao, Yan; Wang, Yun; Hu, Ziheng; Zhu, Zhenyu; Chai, Yifeng

    2016-04-01

    Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound.

  19. Road-Aided Ground Slowly Moving Target 2D Motion Estimation for Single-Channel Synthetic Aperture Radar

    Directory of Open Access Journals (Sweden)

    Zhirui Wang

    2016-03-01

    Full Text Available To detect and estimate ground slowly moving targets in airborne single-channel synthetic aperture radar (SAR, a road-aided ground moving target indication (GMTI algorithm is proposed in this paper. First, the road area is extracted from a focused SAR image based on radar vision. Second, after stationary clutter suppression in the range-Doppler domain, a moving target is detected and located in the image domain via the watershed method. The target’s position on the road as well as its radial velocity can be determined according to the target’s offset distance and traffic rules. Furthermore, the target’s azimuth velocity is estimated based on the road slope obtained via polynomial fitting. Compared with the traditional algorithms, the proposed method can effectively cope with slowly moving targets partly submerged in a stationary clutter spectrum. In addition, the proposed method can be easily extended to a multi-channel system to further improve the performance of clutter suppression and motion estimation. Finally, the results of numerical experiments are provided to demonstrate the effectiveness of the proposed algorithm.

  20. Distinct effects of positive and negative music on older adults' auditory target identification performances.

    Science.gov (United States)

    Vieillard, Sandrine; Bigand, Emmanuel

    2014-01-01

    Older adults, compared to younger adults, are more likely to attend to pleasant situations and avoid unpleasant ones. Yet, it is unclear whether such a phenomenon may be generalized to musical emotions. In this study, we investigated whether there is an age-related difference in how musical emotions are experienced and how positive and negative music influences attention performances in a target identification task. Thirty-one young and twenty-eight older adults were presented with 40 musical excerpts conveying happiness, peacefulness, sadness, and threat. While listening to music, participants were asked to rate their feelings and monitor each excerpt for the occurrence of an auditory target. Compared to younger adults, older adults reported experiencing weaker emotional activation when listening to threatening music and showed higher level of liking for happy music. Correct reaction times (RTs) for target identification were longer for threatening than for happy music in older adults but not in younger adults. This suggests that older adults benefit from a positive musical context and can regulate emotion elicited by negative music by decreasing attention towards it (and therefore towards the auditory target).

  1. Identification of Cell Surface Targets through Meta-analysis of Microarray Data

    Directory of Open Access Journals (Sweden)

    Henry Haeberle

    2012-07-01

    Full Text Available High-resolution image guidance for resection of residual tumor cells would enable more precise and complete excision for more effective treatment of cancers, such as medulloblastoma, the most common pediatric brain cancer. Numerous studies have shown that brain tumor patient outcomes correlate with the precision of resection. To enable guided resection with molecular specificity and cellular resolution, molecular probes that effectively delineate brain tumor boundaries are essential. Therefore, we developed a bioinformatics approach to analyze micro-array datasets for the identification of transcripts that encode candidate cell surface biomarkers that are highly enriched in medulloblastoma. The results identified 380 genes with greater than a two-fold increase in the expression in the medulloblastoma compared with that in the normal cerebellum. To enrich for targets with accessibility for extracellular molecular probes, we further refined this list by filtering it with gene ontology to identify genes with protein localization on, or within, the plasma membrane. To validate this meta-analysis, the top 10 candidates were evaluated with immunohistochemistry. We identified two targets, fibrillin 2 and EphA3, which specifically stain medulloblastoma. These results demonstrate a novel bioinformatics approach that successfully identified cell surface and extracellular candidate markers enriched in medulloblastoma versus adjacent cerebellum. These two proteins are high-value targets for the development of tumor-specific probes in medulloblastoma. This bioinformatics method has broad utility for the identification of accessible molecular targets in a variety of cancers and will enable probe development for guided resection.

  2. In silico re-identification of properties of drug target proteins.

    Science.gov (United States)

    Kim, Baeksoo; Jo, Jihoon; Han, Jonghyun; Park, Chungoo; Lee, Hyunju

    2017-05-31

    Computational approaches in the identification of drug targets are expected to reduce time and effort in drug development. Advances in genomics and proteomics provide the opportunity to uncover properties of druggable genomes. Although several studies have been conducted for distinguishing drug targets from non-drug targets, they mainly focus on the sequences and functional roles of proteins. Many other properties of proteins have not been fully investigated. Using the DrugBank (version 3.0) database containing nearly 6,816 drug entries including 760 FDA-approved drugs and 1822 of their targets and human UniProt/Swiss-Prot databases, we defined 1578 non-redundant drug target and 17,575 non-drug target proteins. To select these non-redundant protein datasets, we built four datasets (A, B, C, and D) by considering clustering of paralogous proteins. We first reassessed the widely used properties of drug target proteins. We confirmed and extended that drug target proteins (1) are likely to have more hydrophobic, less polar, less PEST sequences, and more signal peptide sequences higher and (2) are more involved in enzyme catalysis, oxidation and reduction in cellular respiration, and operational genes. In this study, we proposed new properties (essentiality, expression pattern, PTMs, and solvent accessibility) for effectively identifying drug target proteins. We found that (1) drug targetability and protein essentiality are decoupled, (2) druggability of proteins has high expression level and tissue specificity, and (3) functional post-translational modification residues are enriched in drug target proteins. In addition, to predict the drug targetability of proteins, we exploited two machine learning methods (Support Vector Machine and Random Forest). When we predicted drug targets by combining previously known protein properties and proposed new properties, an F-score of 0.8307 was obtained. When the newly proposed properties are integrated, the prediction performance

  3. Fish species identification based on its acoustic target strength using in situ measurement

    Directory of Open Access Journals (Sweden)

    Raja-Bidin Raja-Hassan

    2010-11-01

    Full Text Available The purpose of this study is fish species identification using acoustic target strength (TS. Insitu measurement has been deployed at the South China Sea of Terengganu Malaysia using Furuno FQ-80 Scientific Echo Sounder which included in the research vessel of KK Senangin II. The transducer isplaced 2.8 meter under sea surface while fish put in the net cage under the vessel. TS data have beencollected independently for commercial fish in Malaysia, there are Selar boops (Oxeye scad, Alepesdjedaba (Shrimp scad, Megalaspis cordyla (Torpedo scad, and Decapterus maruadsi/b> (Japanese scad.TS value, depth, and position of specific target have been observed using echogram. TS of every speciesis different although similar size and at the similar range from transducer. Thus, the specific fish specieshas been identified based on its acoustic target strength.

  4. Identification of septic system effluent in ground water using small catchment hydrochemistry

    Energy Technology Data Exchange (ETDEWEB)

    Foster, M.B.J.; Alexander, E.C. Jr. (Univ. of Minnesota, Minneapolis, MN (United States). Dept. of Geology and Geophysics)

    1992-01-01

    In many areas the contribution of septic system effluent to ground water contamination is still uncertain because of ambiguous provenance of chemical constituents. The problem is to establish a diagnostic chemical signature for the septic system effluent. Chlorides, nitrogen isotopes and optical brighteners have all been used as single constituent tracers for this purpose. These tracers tend to have limited range of application and cannot resolve ambiguity in areas with multiple potential contaminant sources. The authors addressed this problem using eight major ions to characterize the ground water chemistry, graphically or statistically. They identify the chemical signatures of septic system effluent and other non-point source contamination from the ground water chemistry of small ground water catchments overlain by single or very restricted land use types. They studied five small catchments near Rochester, Minnesota to isolate pre-development and non-septic system components of the ground water chemistry. Five small isolated hills were selected each with a distinct land-use type; natural forest, agricultural, unsewered residential, mixed agricultural/residential and fully sewered residential. The results show that Piper diagrams and statistical analysis can be used to define chemical signatures for the unsewered residential area using septic systems, the natural forest, and the agricultural catchments. The signatures of the mixed agriculture/residential and the fully sewered catchments are very similar to that of the agricultural catchment.

  5. Identification of new drug targets and resistance mechanisms in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Thomas R Ioerger

    Full Text Available Identification of new drug targets is vital for the advancement of drug discovery against Mycobacterium tuberculosis, especially given the increase of resistance worldwide to first- and second-line drugs. Because traditional target-based screening has largely proven unsuccessful for antibiotic discovery, we have developed a scalable platform for target identification in M. tuberculosis that is based on whole-cell screening, coupled with whole-genome sequencing of resistant mutants and recombineering to confirm. The method yields targets paired with whole-cell active compounds, which can serve as novel scaffolds for drug development, molecular tools for validation, and/or as ligands for co-crystallization. It may also reveal other information about mechanisms of action, such as activation or efflux. Using this method, we identified resistance-linked genes for eight compounds with anti-tubercular activity. Four of the genes have previously been shown to be essential: AspS, aspartyl-tRNA synthetase, Pks13, a polyketide synthase involved in mycolic acid biosynthesis, MmpL3, a membrane transporter, and EccB3, a component of the ESX-3 type VII secretion system. AspS and Pks13 represent novel targets in protein translation and cell-wall biosynthesis. Both MmpL3 and EccB3 are involved in membrane transport. Pks13, AspS, and EccB3 represent novel candidates not targeted by existing TB drugs, and the availability of whole-cell active inhibitors greatly increases their potential for drug discovery.

  6. Chemogenomics knowledgebase and systems pharmacology for hallucinogen target identification-Salvinorin A as a case study.

    Science.gov (United States)

    Xu, Xiaomeng; Ma, Shifan; Feng, Zhiwei; Hu, Guanxing; Wang, Lirong; Xie, Xiang-Qun

    2016-11-01

    Drug abuse is a serious problem worldwide. Recently, hallucinogens have been reported as a potential preventative and auxiliary therapy for substance abuse. However, the use of hallucinogens as a drug abuse treatment has potential risks, as the fundamental mechanisms of hallucinogens are not clear. So far, no scientific database is available for the mechanism research of hallucinogens. We constructed a hallucinogen-specific chemogenomics database by collecting chemicals, protein targets and pathways closely related to hallucinogens. This information, together with our established computational chemogenomics tools, such as TargetHunter and HTDocking, provided a one-step solution for the mechanism study of hallucinogens. We chose salvinorin A, a potent hallucinogen extracted from the plant Salvia divinorum, as an example to demonstrate the usability of our platform. With the help of HTDocking program, we predicted four novel targets for salvinorin A, including muscarinic acetylcholine receptor 2, cannabinoid receptor 1, cannabinoid receptor 2 and dopamine receptor 2. We looked into the interactions between salvinorin A and the predicted targets. The binding modes, pose and docking scores indicate that salvinorin A may interact with some of these predicted targets. Overall, our database enriched the information of systems pharmacological analysis, target identification and drug discovery for hallucinogens.

  7. Realization to Extend the Orientation Estimation Range of Moving Target on the Ground by a Single Vector Sensor

    Directory of Open Access Journals (Sweden)

    Xiaopeng Song

    2013-07-01

    Full Text Available The DOA (direction of arrival estimation of seismic signals from the moving target on the ground bears great significance for unattended ground systems. The traditional DOA estimation of seismic signals is achieved by a sensor array and its corresponding algorithms. MEMS (Micro-Electro- Mechanical Systems vector vibration sensor, however, gets the vector information over the propagation of seismic signals and therefore can get a DOA estimation within a certain range through a single vector sensor. This paper proposes a new method to extend the orientation range through the rotation of the MEMS vector vibration axis. The experiment shows that this method shares the merits with simple systematic structure, high sensitivity and less than 5 degrees of error on average, which has an extensive wide application prospect.

  8. Atmospheric Effects for Ground Target Signature Modeling. 3. Discussion and Application of the ASL Scattering Model

    Science.gov (United States)

    1975-03-01

    Potential Use of Tactical Microwave Radio (TMR) for Transmission of Weather Radar Data," ECOM-5524, December 1973. 42. Lindberg, James D., and...frared Radiometer ," ECOM-5556, February 1975. 74. Miers, B. T., and H. S. Oey, "An Evaluation of the Hydrometeorological Ground Truth Facility at...Chemical Transport Pgrm Division of Biomedical and Environmental Rsch ATTN: US Atomic Energy Commission Washington, DC 20545 Commander Naval Air

  9. Vision-Based Detection and Tracking of a Mobile Ground Target Using a Fixed-Wing UAV

    Directory of Open Access Journals (Sweden)

    Xun Wang

    2014-09-01

    Full Text Available This paper presents a framework for tracking a mobile ground target (MGT using a fixed-wing unmanned aerial vehicle (UAV. Challenges from pure theories to practical applications, including varying illumination, computational limits and a lack of clarity are considered. The procedure consists of four steps, namely: target detection, target localization, states estimation and UAV guidance. Firstly, the MGT in the wild is separated from the background using a Laplacian operator-based method. Next, the MGT is located by performing coordinate transformations with the assumption that the altitude of the ground is invariant and known. Afterwards, a Kalman filter is used to estimate the location and velocity of the MGT. Finally, a modified guidance law is developed to guide the UAV to circle and track the MGT. The performance of our framework is validated by simulations and a number of actual flight tests. The results indicate that the framework is effective and of low computational complexity, and in particular our modified guidance law can reduce the error of the tracking distance by about 75% in specified situations. With the proposed framework, such challenges caused by the actual system can be tackled effectively, and the fixed-wing UAV can track the MGT stably.

  10. Identification of acceleration pulses in near-fault ground motion using the EMD method

    Institute of Scientific and Technical Information of China (English)

    Zhang Yushan; Hu Yuxian; Zhao Fengxin; Liang Jianwen; Yang Caihong

    2005-01-01

    In this paper, response spectral characteristics of one-, two-, and three-lobe sinusoidal acceleration pulses are investigated, and some of their basic properties are derived. Furthermore, the empirical mode decomposition (EMD) method is utilized as an adaptive filter to decompose the near-fault pulse-like ground motions, which were recorded during the September 20, 1999, Chi-Chi earthquake. These ground motions contain distinct velocity pulses, and were decomposed into high-frequency (HF) and low-frequency (LF) components, from which the corresponding HF acceleration pulse (if existing)and LF acceleration pulse could be easily identified and detected. Finally, the identified acceleration pulses are modeled by simplified sinusoidal approximations, whose dynamic behaviors are compared to those of the original acceleration pulses as well as to those of the original HF and LF acceleration components in the context of elastic response spectra. It was demonstrated that it is just the acceleration pulses contained in the near-fault pulse-like ground motion that fundamentally dominate the special impulsive dynamic behaviors of such motion in an engineering sense. The motion thus has a greater potential to cause severe damage than the far-field ground motions, i.e. they impose high base shear demands on engineering structures as well as placing very high deformation demands on long-period structures.

  11. Neuronal target identification requires AHA-1-mediated fine-tuning of Wnt signaling in C. elegans.

    Directory of Open Access Journals (Sweden)

    Jingyan Zhang

    2013-06-01

    Full Text Available Electrical synaptic transmission through gap junctions is a vital mode of intercellular communication in the nervous system. The mechanism by which reciprocal target cells find each other during the formation of gap junctions, however, is poorly understood. Here we show that gap junctions are formed between BDU interneurons and PLM mechanoreceptors in C. elegans and the connectivity of BDU with PLM is influenced by Wnt signaling. We further identified two PAS-bHLH family transcription factors, AHA-1 and AHR-1, which function cell-autonomously within BDU and PLM to facilitate the target identification process. aha-1 and ahr-1 act genetically upstream of cam-1. CAM-1, a membrane-bound receptor tyrosine kinase, is present on both BDU and PLM cells and likely serves as a Wnt antagonist. By binding to a cis-regulatory element in the cam-1 promoter, AHA-1 enhances cam-1 transcription. Our study reveals a Wnt-dependent fine-tuning mechanism that is crucial for mutual target cell identification during the formation of gap junction connections.

  12. Muddled mechanisms: recent progress towards antimalarial target identification [version 1; referees: 2 approved

    Directory of Open Access Journals (Sweden)

    Rachel L. Edwards

    2016-10-01

    Full Text Available In the past decade, malaria rates have plummeted as a result of aggressive infection control measures and the adoption of artemisinin-based combination therapies (ACTs. However, a potential crisis looms ahead. Treatment failures to standard antimalarial regimens have been reported in Southeast Asia, and devastating consequences are expected if resistance spreads to the African continent. To prevent a potential public health emergency, the antimalarial arsenal must contain therapeutics with novel mechanisms of action (MOA. An impressive number of high-throughput screening (HTS campaigns have since been launched, identifying thousands of compounds with activity against one of the causative agents of malaria, Plasmodium falciparum. Now begins the difficult task of target identification, for which studies are often tedious, labor intensive, and difficult to interpret. In this review, we highlight approaches that have been instrumental in tackling the challenges of target assignment and elucidation of the MOA for hit compounds. Studies that apply these innovative techniques to antimalarial target identification are described, as well as the impact of the data in the field.

  13. Caenorhabditis elegans: A Model System for Anti-Cancer Drug Discovery and Therapeutic Target Identification

    Science.gov (United States)

    Kobet, Robert A.; Pan, Xiaoping; Zhang, Baohong; Pak, Stephen C.; Asch, Adam S.; Lee, Myon-Hee

    2014-01-01

    The nematode Caenorhabditis elegans (C. elegans) offers a unique opportunity for biological and basic medical researches due to its genetic tractability and well-defined developmental lineage. It also provides an exceptional model for genetic, molecular, and cellular analysis of human disease-related genes. Recently, C. elegans has been used as an ideal model for the identification and functional analysis of drugs (or small-molecules) in vivo. In this review, we describe conserved oncogenic signaling pathways (Wnt, Notch, and Ras) and their potential roles in the development of cancer stem cells. During C. elegans germline development, these signaling pathways regulate multiple cellular processes such as germline stem cell niche specification, germline stem cell maintenance, and germ cell fate specification. Therefore, the aberrant regulations of these signaling pathways can cause either loss of germline stem cells or overproliferation of a specific cell type, resulting in sterility. This sterility phenotype allows us to identify drugs that can modulate the oncogenic signaling pathways directly or indirectly through a high-throughput screening. Current in vivo or in vitro screening methods are largely focused on the specific core signaling components. However, this phenotype-based screening will identify drugs that possibly target upstream or downstream of core signaling pathways as well as exclude toxic effects. Although phenotype-based drug screening is ideal, the identification of drug targets is a major challenge. We here introduce a new technique, called Drug Affinity Responsive Target Stability (DARTS). This innovative method is able to identify the target of the identified drug. Importantly, signaling pathways and their regulators in C. elegans are highly conserved in most vertebrates, including humans. Therefore, C. elegans will provide a great opportunity to identify therapeutic drugs and their targets, as well as to understand mechanisms underlying the

  14. Advances in Antisense Oligonucleotide Development for Target Identification, Validation, and as Novel Therapeutics

    Directory of Open Access Journals (Sweden)

    Moizza Mansoor

    2008-01-01

    Full Text Available Antisense oligonucleotides (As-ODNs are single stranded, synthetically prepared strands of deoxynucleotide sequences, usually 18–21 nucleotides in length, complementary to the mRNA sequence of the target gene. As-ODNs are able to selectively bind cognate mRNA sequences by sequence-specific hybridization. This results in cleavage or disablement of the mRNA and, thus, inhibits the expression of the target gene. The specificity of the As approach is based on the probability that, in the human genome, any sequence longer than a minimal number of nucleotides (nt, 13 for RNA and 17 for DNA, normally occurs only once. The potential applications of As-ODNs are numerous because mRNA is ubiquitous and is more accessible to manipulation than DNA. With the publication of the human genome sequence, it has become theoretically possible to inhibit mRNA of almost any gene by As-ODNs, in order to get a better understanding of gene function, investigate its role in disease pathology and to study novel therapeutic targets for the diseases caused by dysregulated gene expression. The conceptual simplicity, the availability of gene sequence information from the human genome, the inexpensive availability of synthetic oligonucleotides and the possibility of rational drug design makes As-ODNs powerful tools for target identification, validation and therapeutic intervention. In this review we discuss the latest developments in antisense oligonucleotide design, delivery, pharmacokinetics and potential side effects, as well as its uses in target identification and validation, and finally focus on the current developments of antisense oligonucleotides in therapeutic intervention in various diseases.

  15. PCR-based ordered genomic libraries: a new approach to drug target identification for Streptococcus pneumoniae.

    Science.gov (United States)

    Belanger, Aimee E; Lai, Angel; Brackman, Marcia A; LeBlanc, Donald J

    2002-08-01

    Described here are the development and validation of a novel approach to identify genes encoding drug targets in Streptococcus pneumoniae. The method relies on the use of an ordered genomic library composed of PCR amplicons that were generated under error-prone conditions so as to introduce random mutations into the DNA. Since some of the mutations occur in drug target-encoding genes and subsequently affect the binding of the drug to its respective cellular target, amplicons containing drug targets can be identified as those producing drug-resistant colonies when transformed into S. pneumoniae. Examination of the genetic content of the amplicon giving resistance coupled with bioinformatics and additional genetic approaches could be used to rapidly identify candidate drug target genes. The utility of this approach was verified by using a number of known antibiotics. For drugs with single protein targets, amplicons were identified that rendered S. pneumoniae drug resistant. Assessment of amplicon composition revealed that each of the relevant amplicons contained the gene encoding the known target for the particular drug tested. Fusidic acid-resistant mutants that resulted from the transformation of S. pneumoniae with amplicons containing fusA were further characterized by sequence analysis. A single mutation was found to occur in a region of the S. pneumoniae elongation factor G protein that is analogous to that already implicated in other bacteria as being associated with fusidic acid resistance. Thus, in addition to facilitating the identification of genes encoding drug targets, this method could provide strains that aid future mechanistic studies.

  16. The gamma Dor CoRoT target HD49434. I-Results from the ground-based campaign

    OpenAIRE

    Uytterhoeven, K.; Mathias, P.; Poretti, E.; RAINER, M.; Martin-Ruiz, S.; Rodriguez, E.; Amado, P. J.; LeContel, D.; Jankov, S.; Niemczura, E.; Pollard, K.; Brunsden, E.; M. Paparo; Costa, V; Valtier, J.-C.

    2008-01-01

    Context: We present the results of an extensive ground-based photometric and spectroscopic campaign on the gamma Dor CoRoT target HD49434. This campaign was preparatory to the CoRoT satellite observations, which took place from October 2007 to March 2008. Results: The frequency analysis clearly shows the presence of four frequencies in the 0.2-1.7 c/d interval, as well as six frequencies in the 5-12 c/d domain. The low frequencies are typical for gamma Dor variables while the high frequencies...

  17. Passive synthetic aperture hitchhiker imaging of ground moving targets--Part 1: image formation and velocity estimation.

    Science.gov (United States)

    Wacks, Steven; Yazici, Birsen

    2014-06-01

    In the Part 1 of this two-part study, we present a method of imaging and velocity estimation of ground moving targets using passive synthetic aperture radar. Such a system uses a network of small, mobile receivers that collect scattered waves due to transmitters of opportunity, such as commercial television, radio, and cell phone towers. Therefore, passive imaging systems have significant cost, manufacturing, and stealth advantages over active systems. We describe a novel generalized Radon transform-type forward model and a corresponding filtered-backprojection-type image formation and velocity estimation method. We form a stack of position images over a range of hypothesized velocities, and show that the targets can be reconstructed at the correct position whenever the hypothesized velocity is equal to the true velocity of targets. We then use entropy to determine the most accurate velocity and image pair for each moving target. We present extensive numerical simulations to verify the reconstruction method. Our method does not require a priori knowledge of transmitter locations and transmitted waveforms. It can determine the location and velocity of multiple targets moving at different velocities. Furthermore, it can accommodate arbitrary imaging geometries. In Part 2, we present the resolution analysis and analysis of positioning errors in passive SAR images due to erroneous velocity estimation.

  18. Identification of Pancreatic Cancer Specific Cell-Surface Markers for Development of Targeting Ligands

    Science.gov (United States)

    Morse, David L.; Hostetter, Galen; Balagurunathan, Yoganand; Gillies, Robert J.; Han, Haiyong

    2014-01-01

    Pancreatic cancer is generally detected at later stages with a poor prognosis and a high-mortality rate. Development of theranostic imaging agents that non-invasively target pancreatic cancer by gene expression and deliver therapies directly to malignant cells could greatly improve therapeutic outcomes. Small-peptide ligands that bind cell-surface proteins and are conjugated to imaging moieties have demonstrated efficacy in cancer imaging. Identification of cancer specific targets is a major bottleneck in the development of such agents. Herein, a method is presented that uses DNA microarray expression profiling of large sets of normal and cancer tissues to identify targets expressed in cancer but not expressed in relevant normal tissues. Identified targets are subsequently validated for protein expression using tissue microarray. Further validations are performed by quantifying expression in pancreatic cancer cells by quantitative real-time reverse-transcription polymerase chain reaction (qRT-PCR), by immunocytochemistry and immunohistochemistry and by reviewing data and literature in public databases. Validated targets are selected for ligand development based on the existence of a known ligand or by known structure activity relationships useful for development of novel ligands. PMID:20217597

  19. Identification of occult breast lesions detected by magnetic resonance imaging with targeted ultrasound: A prospective study

    Energy Technology Data Exchange (ETDEWEB)

    Aracava, Márcia M., E-mail: marcia.aracava@gmail.com; Chojniak, Rubens, E-mail: chojniak@uol.com.br; Souza, Juliana A., E-mail: julianaalves79@hotmail.com; Bitencourt, Almir G.V., E-mail: almirgvb@yahoo.com.br; Marques, Elvira F., E-mail: elvira.marques@ig.com.br

    2014-03-15

    Objective: To verify the capacity of targeted ultrasound (US) to identify additional lesions detected on breast magnetic resonance imaging (MRI), but occult to initial mammography, US and clinical examinations. Methods: This prospective study included 68 additional relevant breast lesions identified on MRI of 49 patients. As an inclusion criterion, breast US and mammography were required and performed up to six months before MRI. These lesions were then subjected to targeted “second-look” US up to 2 weeks after MRI, performed by one or two radiologists with expertise on breast imaging. Lesions were evaluated according to the established Breast Imaging Report and Data System (BI-RADS) lexicon. Results: Targeted US identified 46/68 (67.6%) lesions revealed by MRI. No significant associations were observed between US identification and the type of lesion, dimensions, morphological characteristics and enhancement pattern according to MRI findings. Targeted US identified 100% of BI-RADS category 5 lesions, 90% of category 4 lesions, and just over 50% of category 3 lesions (p < 0.05). There was significant agreement (p < 0.001) between MRI and US BI-RADS classification for all three categories. Conclusion: Targeted US can identify a large proportion of the lesions detected by breast MRI, especially those at high risk of malignancy, when performed by a professional with experience in both breast US and MRI.

  20. Ground-based integrated path coherent differential absorption lidar measurement of CO2: hard target return

    Directory of Open Access Journals (Sweden)

    A. Sato

    2012-11-01

    Full Text Available The National Institute of Information and Communications Technology (NICT have made a great deal of effort to develop a coherent 2-μm differential absorption and wind lidar (Co2DiaWiL for measuring CO2 and wind speed. First, coherent Integrated Path Differential Absorption (IPDA lidar experiments were conducted using the Co2DiaWiL and a hard target (surface return located about 7.12 km south of NICT on 11, 27, and 28 December 2010. The detection sensitivity of a 2-μm IPDA lidar was examined in detail using the CO2 concentration measured by the hard target. The precisions of CO2 measurement for the hard target and 900, 4500 and 27 000 shot pairs were 6.5, 2.8, and 1.2%, respectively. The results indicated that a coherent IPDA lidar with a laser operating at a high pulse repetition frequency of a few tens of KHz is necessary for measuring the CO2 concentration of the hard target with a precision of 1–2 ppm. Statistical comparisons indicated that, although a small amount of in situ data and the fact that they were not co-located with the hard target made comparison difficult, the CO2 volume mixing ratio measured with the Co2DiaWiL was about 5 ppm lower than that measured with the in situ sensor. The statistical results indicated that there were no differences between the hard target and atmospheric return measurements. A precision of 1.5% was achieved from the atmospheric return, which is lower than that obtained from the hard-target returns. Although long-range DIfferential Absorption Lidar (DIAL CO2 measurement with the atmospheric return can result in highly precise measurement, the precision of the atmospheric return measurement was widely distributed comparing to that of the hard target return. Our results indicated that it is important to use a Q-switched laser to measure the range-gated differential absorption optical depth with the atmospheric return and that it is better to simultaneously conduct both hard target and atmospheric return

  1. Characteristics of Hyperspectral Reconnaissance and Threat to Ground Military Targets%高光谱侦察技术特点及其对地面军事目标威胁分析

    Institute of Scientific and Technical Information of China (English)

    麻永平; 张炜; 刘东旭

    2012-01-01

    介绍了高光谱成像探测的原理和特点。给出了国外高光谱侦察技术的发展现状、主要计划项目和趋势。讨论了高光谱侦察技术在战场情报侦察、伪装隐身目标探测,以及机动目标追踪识别等对地面军事目标的侦察威胁。%The principle and characteristics of the hyperspectral imaging detection were introduced in this paper. The development status, main projects and trend of the hyperspectral reconnaissance were presented. The hyperspectral technology in the battlefield intelligence surveillance reconnaissance, camouflage stealth target detection, identification and other aspects of maneuvering target tracking targets on the ground reconnaissance of military threat was discussed.

  2. Classification of ground moving targets using bicepstrum-based features extracted from Micro-Doppler radar signatures

    Science.gov (United States)

    Molchanov, Pavlo O.; Astola, Jaakko T.; Egiazarian, Karen O.; Totsky, Alexander V.

    2013-12-01

    In this article, a novel bicepstrum-based approach is suggested for ground moving radar target classification. Distinctive classification features were extracted from short-time backscattering bispectrum estimates of the micro-Doppler signature. Real radar data were obtained using surveillance Doppler microwave radar operating at 34 GHz. Classifier performance was studied in detail using the Gaussian Mixture Mode and Maximum Likelihood decision making rule, and the results were verified on a multilayer perceptron and Support Vector Machine. Experimental real radar measurements demonstrated that it is quite feasible to discern three classes of humans (single, two and three persons) walking in a vegetation cluttered environment using proposed bicepstrum-based classification features. Sophisticated bispectrum-based signal processing provides the extraction of new classification features in the form of phase relationships in the radar data. It provides a novel insight into moving radar target classification compared to the commonly used energy-based strategy.

  3. Influence of Ground State Spin of Projectile-Target on Fission Anisotropies

    Institute of Scientific and Technical Information of China (English)

    O.N.Ghodsi; A.N.Behkami

    2008-01-01

    Fission fragment anisotropies have been investigated for various systems produced in heavy-ion reactions at near and sub-barrier energies.In particular,special attention has been paid to the entrance channel dependence of fragment angular anisotropies.The results of our analysis of the fragment angular anisotropies induced by boron,carbon,and oxygen ions on Thorium and Neptunium targets as well as Fluorine ions on Neptunium target indicate strong dependence of fragment anisotropies on the channel spin,in consistence with the predication of the pre-equilibrium model.

  4. Multi-primer target PCR for rapid identification of bovine DRB3 alleles.

    Science.gov (United States)

    Ledwidge, S A; Mallard, B A; Gibson, J P; Jansen, G B; Jiang, Z H

    2001-08-01

    Multi-primer target polymerase chain reaction (MPT-PCR) is a rapid method for the identification of specific BoLA-DRB3 alleles. In a single PCR reaction, the presence of two alleles associated with increased risk, DRB3.2*23 (DRB3*2701-2703, 2705-2707) and decreased risk, DRB3.2*16 (DRB3*1501, 1502), of mastitis in Canadian Holstein can be detected. Two outer primers amplify exon 2 of DRB3. Simultaneously, two inner, allele-specific primers amplify individual alleles. Initially, 40 cows previously typed by PCR-restriction fragment length polymorphism (PCR-RFLP) were genotyped using the multi-primer approach. An additional 30 cows were first genotyped by multi-primer target PCR, then by PCR-RFLP. All animals were correctly identified and there were no false positives. This technique can readily be modified to identify other BoLA alleles of interest.

  5. Radio Frequency Identification Sensor Chips with Anticollision Algorithm for Simultaneous Detection of Multiple DNA Targets

    Science.gov (United States)

    Yazawa, Yoshiaki; Oonishi, Tadashi; Watanabe, Kazuki; Nemoto, Ryo; Shiratori, Akiko

    2010-04-01

    A newly developed DNA measurement method for multiple single nucleotide polymorphism (SNP) typing using a radio-frequency identification (RFID) sensor chip was demonstrated. The RFID sensor chip monolithically integrates a sensor, amplifier, analog-to-digital converter (ADC), and a passive wireless communication interface for receiving commands and transmitting data on a 2.5×2.5 mm2 silicon chip. For the simultaneous multitarget measurement, anticollision control and peak-power suppression are essential. To assign a unique identification number (UID) for the identification of multiple sensor chips, a reproducible random number generator circuit (RRG) was designed and installed on the chip. Peak-power consumption was reduced to 1018 µW by a clock gating of functional circuit blocks. Multiple SNP typing was carried out by simultaneously operating five RFID sensor chips (four with photosensors and one with a temperature sensor). The target DNA was captured on the sensor chips, and SNPs were detected by observing bioluminescence. Finally, the observed data were wirelessly transmitted to the reader.

  6. Identification and Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to Castration-Resistant Prostate Cancer

    Science.gov (United States)

    2014-10-01

    propagation. Lgr5+ intestinal stem cells can initiate and maintain murine intestinal adenomas (6, 7). In mouse models of skin cancer, hair follicle bulge...AWARD NUMBER: W81XWH-13-1-0470 TITLE: Identification and Targeting of Candidate Pre... Targeting of Candidate Pre-Existing Lurker Cells that Give Rise to 5a. CONTRACT NUMBER Castration-Resistant Prostate Cancer 5b

  7. A memetic algorithm for path planning of curvature-constrained UAVs performing surveillance of multiple ground targets

    Institute of Scientific and Technical Information of China (English)

    Zhang Xing; Chen Jie; Xin Bin; Peng Zhihong

    2014-01-01

    The problem of generating optimal paths for curvature-constrained unmanned aerial vehicles (UAVs) performing surveillance of multiple ground targets is addressed in this paper. UAVs are modeled as Dubins vehicles so that the constraints of UAVs’ minimal turning radius can be taken into account. In view of the effective surveillance range of the sensors equipped on UAVs, the problem is formulated as a Dubins traveling salesman problem with neighborhood (DTSPN). Considering its prohibitively high computational complexity, the Dubins paths in the sense of terminal heading relaxation are introduced to simplify the calculation of the Dubins distance, and a boundary-based encoding scheme is proposed to determine the visiting point of every target neighborhood. Then, an evolutionary algorithm is used to derive the optimal Dubins tour. To further enhance the quality of the solutions, a local search strategy based on approximate gradient is employed to improve the visiting points of target neighborhoods. Finally, by a minor modification to the individual encoding, the algorithm is easily extended to deal with other two more sophisticated DTSPN variants (multi-UAV scenario and multiple groups of targets scenario). The performance of the algorithm is demonstrated through comparative experiments with other two state-of-the-art DTSPN algorithms identified in literature. Numerical simulations exhibit that the algorithm proposed in this paper can find high-quality solutions to the DTSPN with lower computational cost and produce significantly improved performance over the other algorithms.

  8. A memetic algorithm for path planning of curvature-constrained UAVs performing surveillance of multiple ground targets

    Directory of Open Access Journals (Sweden)

    Zhang Xing

    2014-06-01

    Full Text Available The problem of generating optimal paths for curvature-constrained unmanned aerial vehicles (UAVs performing surveillance of multiple ground targets is addressed in this paper. UAVs are modeled as Dubins vehicles so that the constraints of UAVs’ minimal turning radius can be taken into account. In view of the effective surveillance range of the sensors equipped on UAVs, the problem is formulated as a Dubins traveling salesman problem with neighborhood (DTSPN. Considering its prohibitively high computational complexity, the Dubins paths in the sense of terminal heading relaxation are introduced to simplify the calculation of the Dubins distance, and a boundary-based encoding scheme is proposed to determine the visiting point of every target neighborhood. Then, an evolutionary algorithm is used to derive the optimal Dubins tour. To further enhance the quality of the solutions, a local search strategy based on approximate gradient is employed to improve the visiting points of target neighborhoods. Finally, by a minor modification to the individual encoding, the algorithm is easily extended to deal with other two more sophisticated DTSPN variants (multi-UAV scenario and multiple groups of targets scenario. The performance of the algorithm is demonstrated through comparative experiments with other two state-of-the-art DTSPN algorithms identified in literature. Numerical simulations exhibit that the algorithm proposed in this paper can find high-quality solutions to the DTSPN with lower computational cost and produce significantly improved performance over the other algorithms.

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

    Directory of Open Access Journals (Sweden)

    Li Chenlei

    2014-10-01

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

  10. Identification and targeting leukemia stem cells: The path to the cure for acute myeloid leukemia

    Institute of Scientific and Technical Information of China (English)

    Jianbiao; Zhou; Wee-Joo; Chng

    2014-01-01

    Accumulating evidence support the notion that acute myeloid leukemia(AML) is organized in a hierarchical system, originating from a special proportion of leukemia stem cells(LSC). Similar to their normal counterpart, hematopoietic stem cells(HSC), LSC possess selfrenewal capacity and are responsible for the continued growth and proliferation of the bulk of leukemia cells in the blood and bone marrow. It is believed that LSC are also the root cause for the treatment failure and relapse of AML because LSC are often resistant to chemotherapy. In the past decade, we have made significant advancement in identification and understanding the molecular biology of LSC, but it remains a daunting task to specifically targeting LSC, while sparing normalHSC. In this review, we will first provide a historical overview of the discovery of LSC, followed by a summary of identification and separation of LSC by either cell surface markers or functional assays. Next, the review will focus on the current, various strategies for eradicating LSC. Finally, we will highlight future directions and challenges ahead of our ultimate goal for the cure of AML by targeting LSC.

  11. MAGIC-web: a platform for untargeted and targeted N-linked glycoprotein identification.

    Science.gov (United States)

    Lih, T Mamie; Choong, Wai-Kok; Chen, Chen-Chun; Cheng, Cheng-Wei; Lin, Hsin-Nan; Chen, Ching-Tai; Chang, Hui-Yin; Hsu, Wen-Lian; Sung, Ting-Yi

    2016-07-01

    MAGIC-web is the first web server, to the best of our knowledge, that performs both untargeted and targeted analyses of mass spectrometry-based glycoproteomics data for site-specific N-linked glycoprotein identification. The first two modules, MAGIC and MAGIC+, are designed for untargeted and targeted analysis, respectively. MAGIC is implemented with our previously proposed novel Y1-ion pattern matching method, which adequately detects Y1- and Y0-ion without prior information of proteins and glycans, and then generates in silico MS(2) spectra that serve as input to a database search engine (e.g. Mascot) to search against a large-scale protein sequence database. On top of that, the newly implemented MAGIC+ allows users to determine glycopeptide sequences using their own protein sequence file. The third module, Reports Integrator, provides the service of combining protein identification results from Mascot and glycan-related information from MAGIC-web to generate a complete site-specific protein-glycan summary report. The last module, Glycan Search, is designed for the users who are interested in finding possible glycan structures with specific numbers and types of monosaccharides. The results from MAGIC, MAGIC+ and Reports Integrator can be downloaded via provided links whereas the annotated spectra and glycan structures can be visualized in the browser. MAGIC-web is accessible from http://ms.iis.sinica.edu.tw/MAGIC-web/index.html.

  12. Arctic ecosystem functional zones: identification and quantification using an above and below ground monitoring strategy

    Science.gov (United States)

    Hubbard, Susan S.; Ajo-Franklin, Jonathan B.; Dafflon, Baptiste; Dou, Shan; Kneafsey, Tim J.; Peterson, John E.; Tas, Neslihan; Torn, Margaret S.; Phuong Tran, Anh; Ulrich, Craig; Wainwright, Haruko; Wu, Yuxin; Wullschleger, Stan

    2015-04-01

    Although accurate prediction of ecosystem feedbacks to climate requires characterization of the properties that influence terrestrial carbon cycling, performing such characterization is challenging due to the disparity of scales involved. This is particularly true in vulnerable Arctic ecosystems, where microbial activities leading to the production of greenhouse gasses are a function of small-scale hydrological, geochemical, and thermal conditions influenced by geomorphology and seasonal dynamics. As part of the DOE Next-Generation Ecosystem Experiment (NGEE-Arctic), we are advancing two approaches to improve the characterization of complex Arctic ecosystems, with an initial application to an ice-wedge polygon dominated tundra site near Barrow, AK, USA. The first advance focuses on developing a new strategy to jointly monitor above- and below- ground properties critical for carbon cycling in the tundra. The strategy includes co-characterization of properties within the three critical ecosystem compartments: land surface (vegetation, water inundation, snow thickness, and geomorphology); active layer (peat thickness, soil moisture, soil texture, hydraulic conductivity, soil temperature, and geochemistry); and permafrost (mineral soil and ice content, nature, and distribution). Using a nested sampling strategy, a wide range of measurements have been collected at the study site over the past three years, including: above-ground imagery (LiDAR, visible, near infrared, NDVI) from various platforms, surface geophysical datasets (electrical, electromagnetic, ground penetrating radar, seismic), and point measurements (such as CO2 and methane fluxes, soil properties, microbial community composition). A subset of the coincident datasets is autonomously collected daily. Laboratory experiments and new inversion approaches are used to improve interpretation of the field geophysical datasets in terms of ecosystem properties. The new strategy has significantly advanced our ability

  13. Drug Target Identification and Elucidation of Natural Inhibitors for Bordetella petrii: An In Silico Study

    Science.gov (United States)

    Ray, Manisha; Pattnaik, Animesh; Pradhan, Sukanta Kumar

    2016-01-01

    Environmental microbes like Bordetella petrii has been established as a causative agent for various infectious diseases in human. Again, development of drug resistance in B. petrii challenged to combat against the infection. Identification of potential drug target and proposing a novel lead compound against the pathogen has a great aid and value. In this study, bioinformatics tools and technology have been applied to suggest a potential drug target by screening the proteome information of B. petrii DSM 12804 (accession No. PRJNA28135) from genome database of National Centre for Biotechnology information. In this regards, the inhibitory effect of nine natural compounds like ajoene (Allium sativum), allicin (A. sativum), cinnamaldehyde (Cinnamomum cassia), curcumin (Curcuma longa), gallotannin (active component of green tea and red wine), isoorientin (Anthopterus wardii), isovitexin (A. wardii), neral (Melissa officinalis), and vitexin (A. wardii) have been acknowledged with anti-bacterial properties and hence tested against identified drug target of B. petrii by implicating computational approach. The in silico studies revealed the hypothesis that lpxD could be a potential drug target and with recommendation of a strong inhibitory effect of selected natural compounds against infection caused due to B. petrii, would be further validated through in vitro experiments. PMID:28154518

  14. Approaches for Identification of HIV-1 Entry Inhibitors Targeting gp41 Pocket

    Directory of Open Access Journals (Sweden)

    Asim K. Debnath

    2013-01-01

    Full Text Available The hydrophobic pocket in the HIV-1 gp41 N-terminal heptad repeat (NHR domain plays an important role in viral fusion and entry into the host cell, and serves as an attractive target for development of HIV-1 fusion/entry inhibitors. The peptide anti-HIV drug targeting gp41 NHR, T-20 (generic name: enfuvirtide; brand name: Fuzeon, was approved by the U.S. FDA in 2003 as the first HIV fusion/entry inhibitor for treatment of HIV/AIDS patients who fail to respond to the current antiretroviral drugs. However, because T20 lacks the pocket-binding domain (PBD, it exhibits low anti-HIV-1 activity and short half-life. Therefore, several next-generation HIV fusion inhibitory peptides with PBD have been developed. They possess longer half-life and more potent antiviral activity against a broad spectrum of HIV-1 strains, including the T-20-resistant variants. Nonetheless, the clinical application of these peptides is still limited by the lack of oral availability and the high cost of production. Thus, development of small molecule compounds targeting the gp41 pocket with oral availability has been promoted. This review describes the main approaches for identification of HIV fusion/entry inhibitors targeting the gp41 pocket and summarizes the latest progress in developing these inhibitors as a new class of anti-HIV drugs.

  15. Transcriptome-wide identification of Rauvolfia serpentina microRNAs and prediction of their potential targets.

    Science.gov (United States)

    Prakash, Pravin; Rajakani, Raja; Gupta, Vikrant

    2016-04-01

    MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 19-24 nucleotides (nt) in length and considered as potent regulators of gene expression at transcriptional and post-transcriptional levels. Here we report the identification and characterization of 15 conserved miRNAs belonging to 13 families from Rauvolfia serpentina through in silico analysis of available nucleotide dataset. The identified mature R. serpentina miRNAs (rse-miRNAs) ranged between 20 and 22nt in length, and the average minimal folding free energy index (MFEI) value of rse-miRNA precursor sequences was found to be -0.815 kcal/mol. Using the identified rse-miRNAs as query, their potential targets were predicted in R. serpentina and other plant species. Gene Ontology (GO) annotation showed that predicted targets of rse-miRNAs include transcription factors as well as genes involved in diverse biological processes such as primary and secondary metabolism, stress response, disease resistance, growth, and development. Few rse-miRNAs were predicted to target genes of pharmaceutically important secondary metabolic pathways such as alkaloids and anthocyanin biosynthesis. Phylogenetic analysis showed the evolutionary relationship of rse-miRNAs and their precursor sequences to homologous pre-miRNA sequences from other plant species. The findings under present study besides giving first hand information about R. serpentina miRNAs and their targets, also contributes towards the better understanding of miRNA-mediated gene regulatory processes in plants.

  16. Identification of cell-specific targets of sumoylation during mouse spermatogenesis.

    Science.gov (United States)

    Xiao, Yuxuan; Pollack, Daniel; Andrusier, Miriam; Levy, Avi; Callaway, Myrasol; Nieves, Edward; Reddi, Prabhakara; Vigodner, Margarita

    2016-02-01

    Recent findings suggest diverse and potentially multiple roles of small ubiquitin-like modifier (SUMO) in testicular function and spermatogenesis. However, SUMO targets remain uncharacterized in the testis due to the complex multicellular nature of testicular tissue, the inability to maintain and manipulate spermatogenesis in vitro, and the technical challenges involved in identifying low-abundance endogenous SUMO targets. In this study, we performed cell-specific identification of sumoylated proteins using concentrated cell lysates prepared with de-sumoylation inhibitors from freshly purified spermatocytes and spermatids. One-hundred and twenty proteins were uniquely identified in the spermatocyte and/or spermatid fractions. The identified proteins are involved in the regulation of transcription, stress response, microRNA biogenesis, regulation of major enzymatic pathways, nuclear-cytoplasmic transport, cell-cycle control, acrosome biogenesis, and other processes. Several proteins with important roles during spermatogenesis were chosen for further characterization by co-immunoprecipitation, co-localization, and in vitro sumoylation studies. GPS-SUMO Software was used to identify consensus and non-consensus sumoylation sites within the amino acid sequences of the proteins. The analyses confirmed the cell-specific sumoylation and/or SUMO interaction of several novel, previously uncharacterized SUMO targets such as CDK1, RNAP II, CDC5, MILI, DDX4, TDP-43, and STK31. Furthermore, several proteins that were previously identified as SUMO targets in somatic cells (KAP1 and MDC1) were identified as SUMO targets in germ cells. Many of these proteins have a unique role in spermatogenesis and during meiotic progression. This research opens a novel avenue for further studies of SUMO at the level of individual targets.

  17. Identification of cell-specific targets of sumoylation during mouse spermatogenesis

    Science.gov (United States)

    Xiao, Yuxuan; Pollack, Daniel; Andrusier, Miriam; Levy, Avi; Callaway, Myrasol; Nieves, Edward; Reddi, Prabhakara; Vigodner, Margarita

    2015-01-01

    Recent findings suggest diverse and potentially multiple roles of SUMO in testicular function and spermatogenesis. However, SUMO targets remain uncharacterized in the testis due to the complex multicellular nature of testicular tissue, the inability to maintain and manipulate spermatogenesis in vitro, and the technical challenges involved in identifying low-abundance endogenous SUMO targets. In this study, we performed cell-specific identification of sumoylated proteins using concentrated cell lysates prepared with de-sumoylation inhibitors from freshly purified spermatocytes and spermatids. One-hundred and twenty proteins were uniquely identified in the spermatocyte and/or spermatid fractions. The identified proteins are involved in the regulation of transcription, stress response, microRNA biogenesis, regulation of major enzymatic pathways, nuclear-cytoplasmic transport, cell cycle control, acrosome biogenesis, and other processes. Several proteins with important roles during spermatogenesis were chosen for further characterization by co-immunoprecipitation, co-localization and in-vitro sumoylation studies. GPS-SUMO software was used to identify consensus and non-consensus sumoylation sites within the amino acid sequences of the proteins. The analyses confirmed the cell-specific sumoylation and/or SUMO interaction of several novel, previously uncharacterized SUMO targets such as CDK1, RNAP II, CDC5, MILI, DDX4, TDP-43 and STK31. Furthermore, several proteins that were previously identified as SUMO targets in somatic cells (e.g., KAP1, MDC1) were identified as SUMO targets in germ cells. Many of these proteins have a unique role in spermatogenesis and during meiotic progression. This research opens a novel avenue for further studies of SUMO at the level of individual targets. PMID:26701181

  18. Identification of putative drug targets of Listeria monocytogenes F2365 by subtractive genomics approach

    Directory of Open Access Journals (Sweden)

    Md. Musharaf Hossain

    2013-01-01

    Full Text Available The prolonged and uncontrolled use of antibiotics in treatment against many pathogens causes the multiple drug resistance. The drug resistance of Listeria monocytogenes F2365 has been evolved, which cause a major disease listeriosis. The drug dose limit against that pathogen was also increased for currently prescribed antibiotics and more often combinational therapy was preferred. Therefore, identification of an extensive novel drug target, unique and essential to the microorganism and subjected to its validation and drug development is imperative. Availability of the total proteome of L. monocytogenes F2365 enabled in silico identification of putative common drug targets and their subcellular localization by subtractive genomics approach. In the present work subtractive genomics approach is used to identify vaccine and drug targets of L. monocytogenes F2365 to speed up the rational drug and vaccine design. It has revealed that out of 2821 reference sequences of the pathogen, 744 represent essential proteins and among them 274 are human non-homolog proteins. Besides, all predicted human non-homologs were then analyzed by subcellular localization servers, in which 46 proteins were identified as surface exposed proteins and can be considered as potential drug and vaccine targets for the pathogen. The 3D structure of two human non-homolog putative drug targets, pantothenate kinase (LmPK and holliday junction resolvase-like protein (LmHJR of L. monocytogenes F2365 were generated by homology modeling program Easymodeller 4.0; a GUI version of modeller. Generated structures were also validated by several online servers. The overall stereochemical quality of the model was assessed by Ramachandran plot analysis that was provided by PROCHECK. ProQ, ERRAT, Pro-SA web and VERIFY 3D of SAVES programs were also used to compute several validation parameters during the evaluation of the model. This protein structure information is important in structure

  19. Multi-spectral synthetic image generation for ground vehicle identification training

    Science.gov (United States)

    May, Christopher M.; Pinto, Neil A.; Sanders, Jeffrey S.

    2016-05-01

    There is a ubiquitous and never ending need in the US armed forces for training materials that provide the warfighter with the skills needed to differentiate between friendly and enemy forces on the battlefield. The current state of the art in battlefield identification training is the Recognition of Combat Vehicles (ROC-V) tool created and maintained by the Communications - Electronics Research, Development and Engineering Center Night Vision and Electronic Sensors Directorate (CERDEC NVESD). The ROC-V training package utilizes measured visual and thermal imagery to train soldiers about the critical visual and thermal cues needed to accurately identify modern military vehicles and combatants. This paper presents an approach to augment the existing ROC-V imagery database with synthetically generated multi-spectral imagery that will allow NVESD to provide improved training imagery at significantly lower costs.

  20. Identification of internalizing human single-chain antibodies targeting brain tumor sphere cells.

    Science.gov (United States)

    Zhu, Xiaodong; Bidlingmaier, Scott; Hashizume, Rintaro; James, C David; Berger, Mitchel S; Liu, Bin

    2010-07-01

    Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor for which there is no curative treatment to date. Resistance to conventional therapies and tumor recurrence pose major challenges to treatment and management of this disease, and therefore new therapeutic strategies need to be developed. Previous studies by other investigators have shown that a subpopulation of GBM cells can grow as neurosphere-like cells when cultured in restrictive medium and exhibits enhanced tumor-initiating ability and resistance to therapy. We report here the identification of internalizing human single-chain antibodies (scFv) targeting GBM tumor sphere cells. We selected a large naive phage antibody display library on the glycosylation-dependent CD133 epitope-positive subpopulation of GBM cells grown as tumor spheres and identified internalizing scFvs that target tumor sphere cells broadly, as well as scFvs that target the CD133-positive subpopulation. These scFvs were found to be efficiently internalized by GBM tumor sphere cells. One scFv GC4 inhibited self-renewal of GBM tumor sphere cells in vitro. We have further developed a full-length human IgG1 based on this scFv, and found that it potently inhibits proliferation of GBM tumor sphere cells and GBM cells grown in regular nonselective medium. Taken together, these results show that internalizing human scFvs targeting brain tumor sphere cells can be readily identified from a phage antibody display library, which could be useful for further development of novel therapies that target subpopulations of GBM cells to combat recurrence and resistance to treatment. (c)2010 AACR.

  1. Identification of internalizing human single chain antibodies targeting brain tumor sphere cells

    Science.gov (United States)

    Zhu, Xiaodong; Bidlingmaier, Scott; Hashizume, Rintaro; James, C. David; Berger, Mitchel S.; Liu, Bin

    2010-01-01

    Glioblastoma multiforme (GBM) is the most common and aggressive form of primary brain tumor and there is no curative treatment to date. Resistance to conventional therapies and tumor recurrence pose major challenges to treatment and management of this disease, and therefore new therapeutic strategies need to be developed. Previous studies by other investigators have shown that a subpopulation of GBM cells can grow as neurosphere-like cells when cultured in restrictive media, and exhibit enhanced tumor initiating ability and resistance to therapy. We report here the identification of internalizing human single chain antibodies (scFvs) targeting GBM tumor sphere cells. We selected a large naive phage antibody display library on the glycosylation-dependent CD133 epitope-positive subpopulation of GBM cells grown as tumor spheres and identified internalizing scFvs that target tumor sphere cells broadly, as well as scFvs that target the CD133 positive subpopulation. These scFvs were found to be efficiently internalized by GBM tumor sphere cells. One scFv GC4 inhibited self-renewal of GBM tumor sphere cells in vitro. We have further developed a full-length human IgG1 based on this scFv and found that it potently inhibits proliferation of GBM tumor sphere cells and GBM cells grown in regular non-selective media. Taken together, these results show that internalizing human scFvs targeting brain tumor sphere cells can be readily identified from a phage antibody display library, which could be useful for further development of novel therapies that target subpopulations of GBM cells to combat recurrence and resistance to treatment. PMID:20587664

  2. Configurable adaptive optical system for imaging of ground-based targets from space

    Science.gov (United States)

    McComas, Brian K.; Friedman, Edward J.; Hooker, R. Brian; Cermak, Michael A.

    2003-03-01

    Space-based, high resolution, Earth remote sensing systems, that employ large, flexible, lightweight primary mirrors, will require active wavefront correction, in the form of active and adaptive optics, to correct for thermally and vibrationally induced deformations in the optics. These remote sensing systems typically have a large field-of-view. Unlike the adaptive optics on ground-based astronomical telescopes, which have a negligible field-of-view, the adaptive optics on these space-based remote sensing systems will be required to correct the wavefront over the entire field-of-view, which can be several degrees. The error functions for astronomical adaptive optics have been developed for the narrow field-of-view correction of atmospheric turbulence and do not address the needs of wide field space-based systems. To address these needs, a new wide field adaptive optics theory and a new error function are developed. Modeling and experimental results demonstrate the validity of the wide field adaptive optics theory and new error function. This new error function, which is a new extension of conventional adaptive optics, lead to the development of three new types of imaging systems: wide field-of-view, selectable field-of-view, and steerable field-of-view. These new systems can have nearly diffraction-limited performance across the entire field-of-view or a narrow movable region of high-resolution imaging. The factors limiting system performance will be shown. The range of applicability of the wide field adaptive optics theory is shown. The range of applicability is used to avoid limitations in system performance and to estimate the optical systems parameters, which will meet the system"s performance requirements.

  3. Bioinformatic identification of microRNAs and their target genes from Solanum tuberosum expressed sequence tags

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    MicroRNAs (miRNAs) are a class of non-coding RNAs that regulate gene post-transcriptional expression in plants and animals. Low levels of some miRNAs and time- and tissue-specific expression patterns lead to the difficulty for experimental identification of miRNAs. Here we present a bioinformatic approach for expressed sequence tags (ESTs) prediction of novel miRNAs as well as their targets in Solanum tuberosum. We blasted the databases of S. Tuberosum ESTs to search for potential miRNAs, using previously known miRNA sequences from Arabidopsis, rice and other plant species. By analyzing parameters of plant precursors, including secondary structure, stem length and conservation of miRNAs, and following a variety of filtering criteria, a total of 22 potential miRNAs were detected. Using the newly identified miRNA sequences, we were able to further blast the S. Tuberosum mRNA database and detected 75 potential targets of miRNAs in S. Tuberosum. According to the mRNA annotations provided by the National Center for Biotechnology Information (NCBI) (http://www.ncbi.nlm.nih.gov/), most of the miRNA target genes were predicted to encode transcription factors that regulate cell growth and development, signaling, and metabolism.

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

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    Franciele Maboni Siqueira

    2016-10-01

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

  5. UXO detection and identification based on intrinsic target polarizabilities: A case history

    Energy Technology Data Exchange (ETDEWEB)

    Gasperikova, E.; Smith, J.T.; Morrison, H.F.; Becker, A.; Kappler, K.

    2008-07-15

    Electromagnetic induction data parameterized in time dependent object intrinsic polarizabilities allow discrimination of unexploded ordnance (UXO) from false targets (scrap metal). Data from a cart-mounted system designed for discrimination of UXO with 20 mm to 155 mm diameters are used. Discrimination of UXO from irregular scrap metal is based on the principal dipole polarizabilities of a target. A near-intact UXO displays a single major polarizability coincident with the long axis of the object and two equal smaller transverse polarizabilities, whereas metal scraps have distinct polarizability signatures that rarely mimic those of elongated symmetric bodies. Based on a training data set of known targets, object identification was made by estimating the probability that an object is a single UXO. Our test survey took place on a military base where both 4.2-inch mortar shells and scrap metal were present. The results show that we detected and discriminated correctly all 4.2-inch mortars, and in that process we added 7%, and 17%, respectively, of dry holes (digging scrap) to the total number of excavations in two different survey modes. We also demonstrated a mode of operation that might be more cost effective than the current practice.

  6. Screening and target identification of bioactive compounds that modulate cell migration and autophagy.

    Science.gov (United States)

    Tashiro, Etsu; Imoto, Masaya

    2016-08-01

    Cell migration is a fundamental step for embryonic development, wound repair, immune responses, and tumor cell invasion and metastasis. It is well known that protrusive structures, namely filopodia and lamellipodia, can be observed at the leading edge of migrating cells. The formation of these structures is necessary for cell migration; however, the molecular mechanisms behind the formation of these structures remain largely unclear. Therefore, bioactive compounds that modulate protrusive structures are extremely powerful tools for studying the mechanisms behind the formation of these structures and subsequent cell migration. Therefore, we have screened for bioactive compounds that inhibit the formation of filopodia, lamellipodia, or cell migration from natural products, and attempted to identify the target molecules of our isolated compounds. Additionally, autophagy is a bulk, non-specific protein degradation system that is involved in the pathogenesis of cancer and neurodegenerative disorders. Recent extensive studies have revealed the molecular mechanisms of autophagy, however, they also remain largely unclear. Thus, we also have screened for bioactive compounds that modulate autophagy, and identified the target molecules. In the present article, we introduce the phenotypic screening system and target identification of four bioactive compounds.

  7. Affinity Density: a novel genomic approach to the identification of transcription factor regulatory targets.

    Science.gov (United States)

    Hazelett, Dennis J; Lakeland, Daniel L; Weiss, Joseph B

    2009-07-01

    A new method was developed for identifying novel transcription factor regulatory targets based on calculating Local Affinity Density. Techniques from the signal-processing field were used, in particular the Hann digital filter, to calculate the relative binding affinity of different regions based on previously published in vitro binding data. To illustrate this approach, the complete genomes of Drosophila melanogaster and D.pseudoobscura were analyzed for binding sites of the homeodomain proteinc Tinman, an essential heart development gene in both Drosophila and Mouse. The significant binding regions were identified relative to genomic background and assigned to putative target genes. Valid candidates common to both species of Drosophila were selected as a test of conservation. The new method was more sensitive than cluster searches for conserved binding motifs with respect to positive identification of known Tinman targets. Our Local Affinity Density method also identified a significantly greater proportion of Tinman-coexpressed genes than equivalent, optimized cluster searching. In addition, this new method predicted a significantly greater than expected number of genes with previously published RNAi phenotypes in the heart. Algorithms were implemented in Python, LISP, R and maxima, using MySQL to access locally mirrored sequence data from Ensembl (D.melanogaster release 4.3) and flybase (D.pseudoobscura). All code is licensed under GPL and freely available at http://www.ohsu.edu/cellbio/dev_biol_prog/affinitydensity/.

  8. Genome-wide identification of the regulatory targets of a transcription factor using biochemical characterization and computational genomic analysis

    Directory of Open Access Journals (Sweden)

    Jolly Emmitt R

    2005-11-01

    Full Text Available Abstract Background A major challenge in computational genomics is the development of methodologies that allow accurate genome-wide prediction of the regulatory targets of a transcription factor. We present a method for target identification that combines experimental characterization of binding requirements with computational genomic analysis. Results Our method identified potential target genes of the transcription factor Ndt80, a key transcriptional regulator involved in yeast sporulation, using the combined information of binding affinity, positional distribution, and conservation of the binding sites across multiple species. We have also developed a mathematical approach to compute the false positive rate and the total number of targets in the genome based on the multiple selection criteria. Conclusion We have shown that combining biochemical characterization and computational genomic analysis leads to accurate identification of the genome-wide targets of a transcription factor. The method can be extended to other transcription factors and can complement other genomic approaches to transcriptional regulation.

  9. Identification of target genes of synovial sarcoma-associated fusion oncoprotein using human pluripotent stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Hayakawa, Kazuo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Ikeya, Makoto [Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Fukuta, Makoto [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Woltjen, Knut [Department of Reprogramming Sciences, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Tamaki, Sakura; Takahara, Naoko; Kato, Tomohisa; Sato, Shingo [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Otsuka, Takanobu [Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya (Japan); Toguchida, Junya, E-mail: togjun@frontier.kyoto-u.ac.jp [Department of Tissue Regeneration, Institute for Frontier Medical Sciences, Kyoto University, Kyoto (Japan); Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto (Japan); Department of Orthopaedic Surgery, Graduate School of Medicine, Kyoto University, Kyoto (Japan)

    2013-03-22

    Highlights: ► We tried to identify targets of synovial sarcoma (SS)-associated SYT–SSX fusion gene. ► We established pluripotent stem cell (PSC) lines with inducible SYT–SSX gene. ► SYT–SSX responsive genes were identified by the induction of SYT–SSX in PSC. ► SS-related genes were selected from database by in silico analyses. ► 51 genes were finally identified among SS-related genes as targets of SYT–SSX in PSC. -- Abstract: Synovial sarcoma (SS) is a malignant soft tissue tumor harboring chromosomal translocation t(X; 18)(p11.2; q11.2), which produces SS-specific fusion gene, SYT–SSX. Although precise function of SYT–SSX remains to be investigated, accumulating evidences suggest its role in gene regulation via epigenetic mechanisms, and the product of SYT–SSX target genes may serve as biomarkers of SS. Lack of knowledge about the cell-of-origin of SS, however, has placed obstacle in the way of target identification. Here we report a novel approach to identify SYT–SSX2 target genes using human pluripotent stem cells (hPSCs) containing a doxycycline-inducible SYT–SSX2 gene. SYT–SSX2 was efficiently induced both at mRNA and protein levels within three hours after doxycycline administration, while no morphological change of hPSCs was observed until 24 h. Serial microarray analyses identified genes of which the expression level changed more than twofold within 24 h. Surprisingly, the majority (297/312, 95.2%) were up-regulated genes and a result inconsistent with the current concept of SYT–SSX as a transcriptional repressor. Comparing these genes with SS-related genes which were selected by a series of in silico analyses, 49 and 2 genes were finally identified as candidates of up- and down-regulated target of SYT–SSX, respectively. Association of these genes with SYT–SSX in SS cells was confirmed by knockdown experiments. Expression profiles of SS-related genes in hPSCs and human mesenchymal stem cells (hMSCs) were strikingly

  10. Identification and Characterization of Skin Biomolecules for Drug Targeting and Monitoring by Vibrational Spectroscopy

    Science.gov (United States)

    Eikje, Natalja Skrebova; Aizawa, Katsuo; Sota, Takayuki; Ozaki, Yukihiro; Arase, Seiji

    2008-01-01

    The article discusses the application of vibrational spectroscopy techniques for in vivo identification and characterization of glucose biomolecules monitored in the skin of healthy, prediabetes and diabetes subjects; for molecular characterization of water and proteins in in vivo monitored patch tested inflamed skin of the patients with contact dermatitis; for description of nucleic acids and proteins at the molecular level with progression to malignancy in skin cancerous lesions. The results of the studies show new possibilities to assess activity levels of glucose metabolism in the skin tissue of healthy, prediabetes and diabetes subjects; activity and severity of inflammation; activity of the processes of carcinogenesis with regard to benign, premalignant and malignant transformation. Based on our findings, we suggest that vibrational spectroscopy might be a rapid screening tool with sufficient sensitivity and specificity to identify and characterize skin biomolecules in described diseases for drug targeting and monitoring by the pharmacological community. PMID:19662142

  11. Surface Defect Target Identification on Copper Strip Based on Adaptive Genetic Algorithm and Feature Saliency

    Directory of Open Access Journals (Sweden)

    Xuewu Zhang

    2013-01-01

    Full Text Available To enhance the stability and robustness of visual inspection system (VIS, a new surface defect target identification method for copper strip based on adaptive genetic algorithm (AGA and feature saliency is proposed. First, the study uses gray level cooccurrence matrix (GLCM and HU invariant moments for feature extraction. Then, adaptive genetic algorithm, which is used for feature selection, is evaluated and discussed. In AGA, total error rates and false alarm rates are integrated to calculate the fitness value, and the probability of crossover and mutation is adjusted dynamically according to the fitness value. At last, the selected features are optimized in accordance with feature saliency and are inputted into a support vector machine (SVM. Furthermore, for comparison, we conduct experiments using the selected optimal feature subsequence (OFS and the total feature sequence (TFS separately. The experimental results demonstrate that the proposed method can guarantee the correct rates of classification and can lower the false alarm rates.

  12. Computational Identification of Novel MicroRNAs and Their Targets in Vigna unguiculata.

    Science.gov (United States)

    Lu, Yongzhong; Yang, Xiaoyun

    2010-01-01

    MicroRNAs (miRNAs) are a class of endogenous, noncoding, short RNAs directly involved in regulating gene expression at the posttranscriptional level. High conservation of miRNAs in plant provides the foundation for identification of new miRNAs in other plant species through homology alignment. Here, previous known plant miRNAs were BLASTed against the Expressed Sequence Tag (EST) and Genomic Survey Sequence (GSS) databases of Vigna unguiculata, and according to a series of filtering criteria, a total of 47 miRNAs belonging to 13 miRNA families were identified, and 30 potential target genes of them were subsequently predicted, most of which seemed to encode transcription factors or enzymes participating in regulation of development, growth, metabolism, and other physiological processes. Overall, our findings lay the foundation for further researches of miRNAs function in Vigna unguiculata.

  13. Proteomics meets blood banking: identification of protein targets for the improvement of platelet quality.

    Science.gov (United States)

    Schubert, Peter; Devine, Dana V

    2010-01-01

    Proteomics has brought new perspectives to the fields of hematology and transfusion medicine in the last decade. The steady improvement of proteomic technology is propelling novel discoveries of molecular mechanisms by studying protein expression, post-translational modifications and protein interactions. This review article focuses on the application of proteomics to the identification of molecular mechanisms leading to the deterioration of blood platelets during storage - a critical aspect in the provision of platelet transfusion products. Several proteomic approaches have been employed to analyse changes in the platelet protein profile during storage and the obtained data now need to be translated into platelet biochemistry in order to connect the results to platelet function. Targeted biochemical applications then allow the identification of points for intervention in signal transduction pathways. Once validated and placed in a transfusion context, these data will provide further understanding of the underlying molecular mechanisms leading to platelet storage lesion. Future aspects of proteomics in blood banking will aim to make use of protein markers identified for platelet storage lesion development to monitor proteome changes when alterations such as the use of additive solutions or pathogen reduction strategies are put in place in order to improve platelet quality for patients.

  14. Knowledge-Aided STAP Processing for Ground Moving Target Indication Radar Using Multilook Data

    Directory of Open Access Journals (Sweden)

    Page Douglas

    2006-01-01

    Full Text Available Knowledge-aided space-time adaptive processing (KASTAP using multiple coherent processing interval (CPI radar data is described. The approach is based on forming earth-based clutter reflectivity maps to provide improved knowledge of clutter statistics in nonhomogeneous terrain environments. The maps are utilized to calculate predicted clutter covariance matrices as a function of range. Using a data set provided under the DARPA knowledge-aided sensor signal processing and expert reasoning (KASSPER Program, predicted distributed clutter statistics are compared to measured statistics to verify the accuracy of the approach. Robust STAP weight vectors are calculated using a technique that combines covariance tapering, adaptive estimation of gain and phase corrections, knowledge-aided prewhitening, and eigenvalue rescaling. Techniques to suppress large discrete returns, expected in urban areas, are also described. Several performance metrics are presented, including signal-to-interference-plus-noise ratio (SINR loss, target detections and false alarms, receiver operating characteristic (ROC curves, and tracking performance. The results show more than an order of magnitude reduction in false alarm density when compared to standard STAP processing.

  15. Identification of host-targeted small molecules that restrict intracellular Mycobacterium tuberculosis growth.

    Directory of Open Access Journals (Sweden)

    Sarah A Stanley

    2014-02-01

    Full Text Available Mycobacterium tuberculosis remains a significant threat to global health. Macrophages are the host cell for M. tuberculosis infection, and although bacteria are able to replicate intracellularly under certain conditions, it is also clear that macrophages are capable of killing M. tuberculosis if appropriately activated. The outcome of infection is determined at least in part by the host-pathogen interaction within the macrophage; however, we lack a complete understanding of which host pathways are critical for bacterial survival and replication. To add to our understanding of the molecular processes involved in intracellular infection, we performed a chemical screen using a high-content microscopic assay to identify small molecules that restrict mycobacterial growth in macrophages by targeting host functions and pathways. The identified host-targeted inhibitors restrict bacterial growth exclusively in the context of macrophage infection and predominantly fall into five categories: G-protein coupled receptor modulators, ion channel inhibitors, membrane transport proteins, anti-inflammatories, and kinase modulators. We found that fluoxetine, a selective serotonin reuptake inhibitor, enhances secretion of pro-inflammatory cytokine TNF-α and induces autophagy in infected macrophages, and gefitinib, an inhibitor of the Epidermal Growth Factor Receptor (EGFR, also activates autophagy and restricts growth. We demonstrate that during infection signaling through EGFR activates a p38 MAPK signaling pathway that prevents macrophages from effectively responding to infection. Inhibition of this pathway using gefitinib during in vivo infection reduces growth of M. tuberculosis in the lungs of infected mice. Our results support the concept that screening for inhibitors using intracellular models results in the identification of tool compounds for probing pathways during in vivo infection and may also result in the identification of new anti

  16. Identification and Characterization of MicroRNAs and Their Targets in Grapevine ( Vitis vinifera)

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    MicroRNAs (miRNAs) are a class of newly identified, small, non-coding RNAs that play vital roles in regulation. Based on miRNAs unique features of expression pattern, evolutionary conservation, secondary structure and genetic requirements for biogenesis, computational predication strategy is adopted to predicate the novel miRNAs. In this research, potential miRNAs and their targets in grapevine (Vitis vinifera) were predicted. We used previously known plant miRNAs against grapevine genome sequence databases to search for potential miRNAs. A total of 81 potential miRNAs were detected following a range of strict filtering criteria. Using these potential miRNA sequences, we could further blast the mRNA database to find the potential targets in this species. Comparative analysis of miRNAs in grapevine and other species reveals that miRNAs exhibit an evolutional conservation, the number and function of miRNAs must have significantly expanded during the evolution of land plants. Furthermore divergence made versatile functions of miRNAs feasible. Cluster of miRNAs likely represents an ancient expression mechanism. Predicted target genes include not only transcription factors but also genes implicated in floral development, signal transduction, diseases and stress response. Till now, little is known about experimental or computational identification of miRNA in grapevine species. Increased knowledge of the biological mechanisms of the grapevine will allow targeted approaches to increase the quality of fruit and reduce the impact of parasites together with stress, which could enable a sustainable, environmentally-sound, farming policy.

  17. Using Ground Targets to Validate S-NPP VIIRS Day-Night Band Calibration

    Directory of Open Access Journals (Sweden)

    Xuexia Chen

    2016-11-01

    Full Text Available In this study, the observations from S-NPP VIIRS Day-Night band (DNB and Moderate resolution bands (M bands of Libya 4 and Dome C over the first four years of the mission are used to assess the DNB low gain calibration stability. The Sensor Data Records produced by NASA Land Product Evaluation and Algorithm Testing Element (PEATE are acquired from nearly nadir overpasses for Libya 4 desert and Dome C snow surfaces. A kernel-driven bidirectional reflectance distribution function (BRDF correction model is used for both Libya 4 and Dome C sites to correct the surface BRDF influence. At both sites, the simulated top-of-atmosphere (TOA DNB reflectances based on SCIAMACHY spectral data are compared with Land PEATE TOA reflectances based on modulated Relative Spectral Response (RSR. In the Libya 4 site, the results indicate a decrease of 1.03% in Land PEATE TOA reflectance and a decrease of 1.01% in SCIAMACHY derived TOA reflectance over the period from April 2012 to January 2016. In the Dome C site, the decreases are 0.29% and 0.14%, respectively. The consistency between SCIAMACHY and Land PEATE data trends is good. The small difference between SCIAMACHY and Land PEATE derived TOA reflectances could be caused by changes in the surface targets, atmosphere status, and on-orbit calibration. The reflectances and radiances of Land PEATE DNB are also compared with matching M bands and the integral M bands based on M4, M5, and M7. The fitting trends of the DNB to integral M bands ratios indicate a 0.75% decrease at the Libya 4 site and a 1.89% decrease at the Dome C site. Part of the difference is due to an insufficient number of sampled bands available within the DNB wavelength range. The above results indicate that the Land PEATE VIIRS DNB product is accurate and stable. The methods used in this study can be used on other satellite instruments to provide quantitative assessments for calibration stability.

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

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    Yang Zhang

    2016-10-01

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

  19. Different acute toxicity of fipronil baits on invasive Linepithema humile supercolonies and some non-target ground arthropods.

    Science.gov (United States)

    Hayasaka, Daisuke; Kuwayama, Naoki; Takeo, Azuma; Ishida, Takanobu; Mano, Hiroyuki; Inoue, Maki N; Nagai, Takashi; Sánchez-Bayo, Francisco; Goka, Koichi; Sawahata, Takuo

    2015-08-01

    Fipronil is one of the most effective insecticides to control the invasive ant Linepithema humile, but its effectiveness has been assessed without considering the genetic differences among L. humile supercolonies. We hypothesized that the susceptibility of the ant to fipronil might differ among supercolonies. If so, dosage and concentration of fipronil may need to be adjusted for effective eradication of each supercolony. The relative sensitivities of four L. humile supercolonies established in Hyogo (Japan) to fipronil baits were examined based on their acute toxicity (48-h LC(50)). Toxicities of fipronil to seven ground arthropods, including four native ant species, one native isopoda, and two cockroaches were also determined and compared to that of L. humile supercolonies using species sensitivity distributions. Marked differences in susceptibility of fipronil were apparent among the supercolonies (P non-target species (330-2327 μg L(-1)) were in the same range as that of L. humile, and SSDs between the two species groups were not significantly different (t = -1.389, P = 0.180), suggesting that fipronil's insecticidal activity is practically the same for L. humile as for non-target arthropods. Therefore, if the invasive ant is to be controlled using fipronil, this would also affect the local arthropod biodiversity. Only the 'Japanese main supercolony' can be controlled with appropriate bait dosages of fipronil that would have little impact on the other species.

  20. Identification and description of potential ground-water quality monitoring wells in Florida

    Science.gov (United States)

    Seaber, P.R.; Thagard, M.E.

    1986-01-01

    characteristics throughout the State. The identification and description of the potential monitoring wells and the listing of the type and frequency of the groundwater quality data forms a foundation for both the network and the data base. (Author 's abstract)

  1. Identification and sensitivity analysis of a correlated ground rule system (design arc)

    Science.gov (United States)

    Eastman, Eric; Chidambarrao, Dureseti; Rausch, Werner; Topaloglu, Rasit O.; Shao, Dongbing; Ramachandran, Ravikumar; Angyal, Matthew

    2017-04-01

    We demonstrate a tool which can function as an interface between VLSI designers and process-technology engineers throughout the Design-Technology Co-optimization (DTCO) process. This tool uses a Monte Carlo algorithm on the output of lithography simulations to model the frequency of fail mechanisms on wafer. Fail mechanisms are defined according to process integration flow: by Boolean operations and measurements between original and derived shapes. Another feature of this design rule optimization methodology is the use of a Markov-Chain-based algorithm to perform a sensitivity analysis, the output of which may be used by process engineers to target key process-induced variabilities for improvement. This tool is used to analyze multiple Middle-Of-Line fail mechanisms in a 10nm inverter design and identify key process assumptions that will most strongly affect the yield of the structures. This tool and the underlying algorithm are also shown to be scalable to arbitrarily complex geometries in three dimensions. Such a characteristic which is becoming more important with the introduction of novel patterning technologies and more complex 3-D on-wafer structures.

  2. High-Throughput Screening Strategies for Targeted Identification Small-Molecule Compounds Towards Activated Pathways in Colorectal Cancer

    OpenAIRE

    Bialkowska, Agnieszka B.; Yang, Vincent W

    2012-01-01

    Recent advancement in understanding the role of both the genetics and molecular pathways in the formation and progression of colorectal cancer allowed the identification of factors that may be targeted for drug discovery. For the past decade various approaches have been developed to target specific steps or components of these pathways in order to prevent the development or progression of colorectal cancer. The innovation and optimization of high-throughput screening methods as well as the re...

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

    Directory of Open Access Journals (Sweden)

    Anna Frenzel

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

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

    Science.gov (United States)

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

    2011-01-01

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

  5. Metabolic pathway analysis approach: identification of novel therapeutic target against methicillin resistant Staphylococcus aureus.

    Science.gov (United States)

    Uddin, Reaz; Saeed, Kiran; Khan, Waqasuddin; Azam, Syed Sikander; Wadood, Abdul

    2015-02-10

    identified by not only superimposing the template structure (PDB ID: 1E0A) over each other but also by the Parallel-ProBiS algorithm. The identified active site was further validated by cross-docking the co-crystallized ligand (2-oxoglutaric acid; AKG) of PDB ID: 1LLW. It was concluded that the comparative metabolic in silico analysis together with structure-based methods provides an effective approach for the identification of novel antibiotic targets against MRSA.

  6. Comparative genomics allowed the identification of drug targets against human fungal pathogens

    Directory of Open Access Journals (Sweden)

    Martins Natalia F

    2011-01-01

    Full Text Available Abstract Background The prevalence of invasive fungal infections (IFIs has increased steadily worldwide in the last few decades. Particularly, there has been a global rise in the number of infections among immunosuppressed people. These patients present severe clinical forms of the infections, which are commonly fatal, and they are more susceptible to opportunistic fungal infections than non-immunocompromised people. IFIs have historically been associated with high morbidity and mortality, partly because of the limitations of available antifungal therapies, including side effects, toxicities, drug interactions and antifungal resistance. Thus, the search for alternative therapies and/or the development of more specific drugs is a challenge that needs to be met. Genomics has created new ways of examining genes, which open new strategies for drug development and control of human diseases. Results In silico analyses and manual mining selected initially 57 potential drug targets, based on 55 genes experimentally confirmed as essential for Candida albicans or Aspergillus fumigatus and other 2 genes (kre2 and erg6 relevant for fungal survival within the host. Orthologs for those 57 potential targets were also identified in eight human fungal pathogens (C. albicans, A. fumigatus, Blastomyces dermatitidis, Paracoccidioides brasiliensis, Paracoccidioides lutzii, Coccidioides immitis, Cryptococcus neoformans and Histoplasma capsulatum. Of those, 10 genes were present in all pathogenic fungi analyzed and absent in the human genome. We focused on four candidates: trr1 that encodes for thioredoxin reductase, rim8 that encodes for a protein involved in the proteolytic activation of a transcriptional factor in response to alkaline pH, kre2 that encodes for α-1,2-mannosyltransferase and erg6 that encodes for Δ(24-sterol C-methyltransferase. Conclusions Our data show that the comparative genomics analysis of eight fungal pathogens enabled the identification of

  7. Plant microRNA-target interaction identification model based on the integration of prediction tools and support vector machine.

    Directory of Open Access Journals (Sweden)

    Jun Meng

    Full Text Available Confident identification of microRNA-target interactions is significant for studying the function of microRNA (miRNA. Although some computational miRNA target prediction methods have been proposed for plants, results of various methods tend to be inconsistent and usually lead to more false positive. To address these issues, we developed an integrated model for identifying plant miRNA-target interactions.Three online miRNA target prediction toolkits and machine learning algorithms were integrated to identify and analyze Arabidopsis thaliana miRNA-target interactions. Principle component analysis (PCA feature extraction and self-training technology were introduced to improve the performance. Results showed that the proposed model outperformed the previously existing methods. The results were validated by using degradome sequencing supported Arabidopsis thaliana miRNA-target interactions. The proposed model constructed on Arabidopsis thaliana was run over Oryza sativa and Vitis vinifera to demonstrate that our model is effective for other plant species.The integrated model of online predictors and local PCA-SVM classifier gained credible and high quality miRNA-target interactions. The supervised learning algorithm of PCA-SVM classifier was employed in plant miRNA target identification for the first time. Its performance can be substantially improved if more experimentally proved training samples are provided.

  8. A distributed computational search strategy for the identification of diagnostics targets: application to finding aptamer targets for methicillin-resistant staphylococci.

    Science.gov (United States)

    Flanagan, Keith; Cockell, Simon; Harwood, Colin; Hallinan, Jennifer; Nakjang, Sirintra; Lawry, Beth; Wipat, Anil

    2014-06-30

    The rapid and cost-effective identification of bacterial species is crucial, especially for clinical diagnosis and treatment. Peptide aptamers have been shown to be valuable for use as a component of novel, direct detection methods. These small peptides have a number of advantages over antibodies, including greater specificity and longer shelf life. These properties facilitate their use as the detector components of biosensor devices. However, the identification of suitable aptamer targets for particular groups of organisms is challenging. We present a semi-automated processing pipeline for the identification of candidate aptamer targets from whole bacterial genome sequences. The pipeline can be configured to search for protein sequence fragments that uniquely identify a set of strains of interest. The system is also capable of identifying additional organisms that may be of interest due to their possession of protein fragments in common with the initial set. Through the use of Cloud computing technology and distributed databases, our system is capable of scaling with the rapidly growing genome repositories, and consequently of keeping the resulting data sets up-to-date. The system described is also more generically applicable to the discovery of specific targets for other diagnostic approaches such as DNA probes, PCR primers and antibodies.

  9. Identification of human embryonic progenitor cell targeting peptides using phage display.

    Directory of Open Access Journals (Sweden)

    Paola A Bignone

    Full Text Available Human pluripotent stem (hPS cells are capable of differentiation into derivatives of all three primary embryonic germ layers and can self-renew indefinitely. They therefore offer a potentially scalable source of replacement cells to treat a variety of degenerative diseases. The ability to reprogram adult cells to induced pluripotent stem (iPS cells has now enabled the possibility of patient-specific hPS cells as a source of cells for disease modeling, drug discovery, and potentially, cell replacement therapies. While reprogramming technology has dramatically increased the availability of normal and diseased hPS cell lines for basic research, a major bottleneck is the critical unmet need for more efficient methods of deriving well-defined cell populations from hPS cells. Phage display is a powerful method for selecting affinity ligands that could be used for identifying and potentially purifying a variety of cell types derived from hPS cells. However, identification of specific progenitor cell-binding peptides using phage display may be hindered by the large cellular heterogeneity present in differentiating hPS cell populations. We therefore tested the hypothesis that peptides selected for their ability to bind a clonal cell line derived from hPS cells would bind early progenitor cell types emerging from differentiating hPS cells. The human embryonic stem (hES cell-derived embryonic progenitor cell line, W10, was used and cell-targeting peptides were identified. Competition studies demonstrated specificity of peptide binding to the target cell surface. Efficient peptide targeted cell labeling was accomplished using multivalent peptide-quantum dot complexes as detected by fluorescence microscopy and flow cytometry. The cell-binding peptides were selective for differentiated hPS cells, had little or no binding on pluripotent cells, but preferential binding to certain embryonic progenitor cell lines and early endodermal hPS cell derivatives. Taken

  10. Dynamic FLIR Target Acquisition. Phase I.

    Science.gov (United States)

    1978-08-02

    eas re: e r- tecr- ’t(, es will be ised for the Phase st Cy. 5.3.2 :ae Vnar -oles These v~r ies relate to the im.age characteristics which are...ground target detection and identification, TM 1-62, Aberdeen Proving Grounds, MD: Human Engineering Laboratories, Jan. 1962, (AD273696). Nygaand, J. E

  11. Identification of direct regulatory targets of the transcription factor Sox10 based on function and conservation

    Directory of Open Access Journals (Sweden)

    Lee Sanghyuk

    2008-09-01

    Full Text Available Abstract Background Sox10, a member of the Sry-related HMG-Box gene family, is a critical transcription factor for several important cell lineages, most notably the neural crest stem cells and the derivative peripheral glial cells and melanocytes. Thus far, only a handful of direct target genes are known for this transcription factor limiting our understanding of the biological network it governs. Results We describe identification of multiple direct regulatory target genes of Sox10 through a procedure based on function and conservation. By combining RNA interference technique and DNA microarray technology, we have identified a set of genes that show significant down-regulation upon introduction of Sox10 specific siRNA into Schwannoma cells. Subsequent comparative genomics analyses led to potential binding sites for Sox10 protein conserved across several mammalian species within the genomic region proximal to these genes. Multiple sites belonging to 4 different genes (proteolipid protein, Sox10, extracellular superoxide dismutase, and pleiotrophin were shown to directly interact with Sox10 by chromatin immunoprecipitation assay. We further confirmed the direct regulation through the identified cis-element for one of the genes, extracellular superoxide dismutase, using electrophoretic mobility shift assay and reporter assay. Conclusion In sum, the process of combining differential expression profiling and comparative genomics successfully led to further defining the role of Sox10, a critical transcription factor for the development of peripheral glia. Our strategy utilizing relatively accessible techniques and tools should be applicable to studying the function of other transcription factors.

  12. Ground-based characterization of Eurybates and Orus, two fly-by targets of the Lucy Discovery mission

    Science.gov (United States)

    Mottola, Stefano; Marchi, Simone; Buie, Marc W.; Hellmich, Stephan; Di Martino, Mario; Proffe, Gerrit; Levison, Harold F.; Zangari, Amanda Marie

    2016-10-01

    Lucy is a proposed NASA Discovery mission designed to perform close fly-bys with six Jupiter Trojan asteroids. The mission, which is currently in the Phase A development phase, is planned to launch in 2021 and arrive at the Trojan L4 cloud in 2027.We report on ground-based light curve observations of two of Lucy's fly-by target candidates: (3548) Eurybates and (21900) Orus. The goal is to characterize their shape, spin state and photometric properties both to aid in the planning of the mission, and to complement the space-borne data.Each object has been observed over 5 apparitions in a wide range of geocentric ecliptic longitudes. Shape and spin state modeling was performed by using the convex shape inversion method (Kaasalainen, Mottola & Fulchignoni, 2002). Eurybates is a retrograde rotator with a sidereal rotation Psid=8.702724±0.000009 h. It has a moderately elongated shape with equivalent axial ratios a/b=1.08, b/c=1.16. No obvious signs of global non-convexities and/or albedo variegation are detected in its light curves. Orus is also a retrograde rotator with a period Psid=13.48617±0.00007 h. Its approximate axial ratios are a/b=1.14, b/c=1.12. The presence of a large, planar facet in the proximity of the model's North Pole suggests the presence of a large polar crater.

  13. Cultural Marker Identification for Web Application Design Targeted for Malaysian Multicultural Users

    Directory of Open Access Journals (Sweden)

    Norliza Saidin

    2016-12-01

    Full Text Available The rapid growth of technology result in two contradictory phenomenon, the global world becomes smaller while the internet users increase drastically. This diversity of users becomes the main attention toward the study of human computer interaction due to the influential of users’ background toward the usability of web application whereby combination of color strongly determine user’s preference and engagement level.  Hence, determination of color based cultural marker is crucial to the interface design process in order to fulfill the need of diverse users. Most of the empirical study so far has been carried in western contextual. As a result, suggested marker are not applicable in eastern perspective, particularly Malaysia which consist of multicultural society. This article provides content analysis of the website application targeted to multicultural audience to determine the prominent color based cultural markers. More importantly, identifications of the markers could assist the interface designers towards creating web based application that reflected the multicultural audience preferences.

  14. Computational identification of microRNAs and their targets in wheat (Triticum aestivum L.)

    Institute of Scientific and Technical Information of China (English)

    HAN YouSheng; LUAN FuLei; ZHU HongLiang; SHAO Yi; CHEN AnJun; LU ChengWen; LUO YunBo; ZHU BenZhong

    2009-01-01

    microRNAs (miRNAs)are a class of endogenous,non-coding,short (-21 nt)RNAs directly involved in regulating gene expression at the post-transcriptional level.Previous reports have noted that plant miRNAs in the plant kingdom are highly conserved,which provides the foundation for identification of conserved miRNAs in other plant species through homology alignment.Conserved miRNAs in wheat are identified using EST (Expressed Sequence Tags)and GSS analysis.All previously known miRNAs in other plant species were blasted against wheat EST and GSS sequences to select novel miRNAs in wheat by a series of filtering criteria.From a total of 37 conserved miRNAs belonging to 18 miRNA families 10 conserved miRNAs comprising 4 families were reported in wheat.MiR395 is found to be a special family,because three members belonging to the same miR395 family are clustered together,similar to animal miRNAs.MiRNA targets are transcription factors involved in wheat growth and development,metabolism,and stress responses.

  15. Computational identification of microRNAs and their targets in wheat (Triticum aestivum L.)

    Institute of Scientific and Technical Information of China (English)

    2009-01-01

    microRNAs (miRNAs) are a class of endogenous, non-coding, short (~21 nt) RNAs directly involved in regulating gene expression at the post-transcriptional level. Previous reports have noted that plant miRNAs in the plant kingdom are highly conserved, which provides the foundation for identification of conserved miRNAs in other plant species through homology alignment. Conserved miRNAs in wheat are identified using EST (Expressed Sequence Tags) and GSS analysis. All previously known miRNAs in other plant species were blasted against wheat EST and GSS sequences to select novel miRNAs in wheat by a series of filtering criteria. From a total of 37 conserved miRNAs belonging to 18 miRNA families 10 conserved miRNAs comprising 4 families were reported in wheat. MiR395 is found to be a special family, because three members belonging to the same miR395 family are clustered together, similar to animal miRNAs. MiRNA targets are transcription factors involved in wheat growth and development, metabolism,and stress responses.

  16. Nested polymerase chain reaction (PCR) targeting 16S rDNA for bacterial identification in empyema.

    Science.gov (United States)

    Prasad, Rajniti; Kumari, Chhaya; Das, B K; Nath, Gopal

    2014-05-01

    Empyema in children causes significant morbidity and mortality. However, identification of organisms is a major concern. To detect bacterial pathogens in pus specimens of children with empyema by 16S rDNA nested polymerase chain reaction (PCR) and correlate it with culture and sensitivity. Sixty-six children admitted to the paediatric ward with a diagnosis of empyema were enrolled prospectively. Aspirated pus was subjected to cytochemical examination, culture and sensitivity, and nested PCR targeting 16S rDNA using a universal eubacterial primer. Mean (SD) age was 5·8 (1·8) years (range 1-13). Analysis of aspirated pus demonstrated total leucocyte count >1000×10(6)/L, elevated protein (≧20 g/L) and decreased glucose (≤2·2 mmol/L) in 80·3%, 98·5% and 100%, respectively. Gram-positive cocci were detected in 29 (43·9%) and Gram-negative bacilli in two patients. Nested PCR for the presence of bacterial pathogens was positive in 50·0%, compared with 36·3% for culture. 16S rDNA PCR improves rates of detection of bacteria in pleural fluid, and can detect bacterial species in a single assay as well as identifying unusual and unexpected causal agents.

  17. Single Phase-to-Ground Fault Line Identification and Section Location Method for Non-Effectively Grounded Distribution Systems Based on Signal Injection

    Institute of Scientific and Technical Information of China (English)

    PAN Zhencun; WANG Chengshan; CONG Wei; ZHANG Fan

    2008-01-01

    A diagnostic signal current trace detecting based single phase-to-ground fault line identifica- tion and section location method for non-effectively grounded distribution systems is presented in thisi oaper. A special diagnostic signal current is injected into the fault distribution system, and then it is de- tected at the outlet terminals to identify the fault line and at the sectionalizing or branching point along the fault line to locate the fault section. The method has been put into application in actual distribution network and field experience shows that it can identify the fault line and locate the fault section correctly and effectively.

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

    Directory of Open Access Journals (Sweden)

    Yoon-Dong Park

    2016-08-01

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

  19. Identification of ligand-target pairs from combined libraries of small molecules and unpurified protein targets in cell lysates.

    Science.gov (United States)

    McGregor, Lynn M; Jain, Tara; Liu, David R

    2014-02-26

    We describe the development and validation of interaction determination using unpurified proteins (IDUP), a method that selectively amplifies DNA sequences identifying ligand+target pairs from a mixture of DNA-linked small molecules and unpurified protein targets in cell lysates. By operating in cell lysates, IDUP preserves native post-translational modifications and interactions with endogenous binding partners, thereby enabling the study of difficult-to-purify targets and increasing the potential biological relevance of detected interactions compared with methods that require purified proteins. In IDUP, target proteins are associated with DNA oligonucleotide tags either non-covalently using a DNA-linked antibody or covalently using a SNAP-tag. Ligand-target binding promotes hybridization of a self-priming hairpin that is extended by a DNA polymerase to create a DNA strand that contains sequences identifying both the target and its ligand. These sequences encoding ligand+target pairs are selectively amplified by PCR and revealed by high-throughput DNA sequencing. IDUP can respond to the effect of affinity-modulating adaptor proteins in cell lysates that would be absent in ligand screening or selection methods using a purified protein target. This capability was exemplified by the 100-fold amplification of DNA sequences encoding FRB+rapamycin or FKBP+rapamycin in samples overexpressing both FRB and FKBP (FRB·rapamycin+FKBP, Kd ≈ 100 fM; FKBP·rapamycin+FRB, Kd = 12 nM). In contrast, these sequences were amplified 10-fold less efficiently in samples overexpressing either FRB or FKBP alone (rapamycin+FKBP, Kd ≈ 0.2 nM; rapamcyin+FRB, Kd = 26 μM). Finally, IDUP was used to process a model library of DNA-linked small molecules and a model library of cell lysates expressing SNAP-target fusions combined in a single sample. In this library×library experiment, IDUP resulted in enrichment of sequences corresponding to five known ligand+target pairs ranging in binding

  20. A fast Fourier transform (FFT)-based along track interferometry (ATI) approach to SAR-based ground moving target indication (GMTI)

    Science.gov (United States)

    Thomas, Daniel D.; Zhang, Yuhong

    2014-06-01

    Along-track interferometry (ATI) is used to detect ground moving targets against a stationary background in synthetic aperture radar (SAR) imagery. In this paper, we present a novel approach to multi-channel ATI wherein clutter cancellation is applied to each pixel of the multiple SAR images, followed by a Fourier transform to estimate range rate (Doppler). Range rate estimates allow us to compensate for the cross-range offset of the target, thus geo-locating the targets. We then present a number of benefits to this approach.

  1. Targeted oligonucleotide-mediated microsatellite identification (TOMMI from large-insert library clones

    Directory of Open Access Journals (Sweden)

    Ren Jun

    2005-11-01

    Full Text Available Abstract Background In the last few years, microsatellites have become the most popular molecular marker system and have intensively been applied in genome mapping, biodiversity and phylogeny studies of livestock. Compared to single nucleotide polymorphism (SNP as another popular marker system, microsatellites reveal obvious advantages. They are multi-allelic, possibly more polymorphic and cheaper to genotype. Calculations showed that a multi-allelic marker system always has more power to detect Linkage Disequilibrium (LD than does a di-allelic marker system 1. Traditional isolation methods using partial genomic libraries are time-consuming and cost-intensive. In order to directly generate microsatellites from large-insert libraries a sequencing approach with repeat-containing oligonucleotides is introduced. Results Seventeen porcine microsatellite markers were isolated from eleven PAC clones by targeted oligonucleotide-mediated microsatellite identification (TOMMI, an improved efficient and rapid flanking sequence-based approach for the isolation of STS-markers. With the application of TOMMI, an average of 1.55 (CA/GT microsatellites per PAC clone was identified. The number of alleles, allele size distribution, polymorphism information content (PIC, average heterozygosity (HT, and effective allele number (NE for the STS-markers were calculated using a sampling of 336 unrelated animals representing fifteen pig breeds (nine European and six Chinese breeds. Sixteen of the microsatellite markers proved to be polymorphic (2 to 22 alleles in this heterogeneous sampling. Most of the publicly available (porcine microsatellite amplicons range from approximately 80 bp to 200 bp. Here, we attempted to utilize as much sequence information as possible to develop STS-markers with larger amplicons. Indeed, fourteen of the seventeen STS-marker amplicons have minimal allele sizes of at least 200 bp. Thus, most of the generated STS-markers can easily be

  2. Identification of metE as a Second Target of the sRNA scr5239 in Streptomyces coelicolor

    OpenAIRE

    Michael-Paul Vockenhuber; Nona Heueis; Beatrix Suess

    2015-01-01

    While transcriptional regulation of the primary and secondary metabolism of the model organism Streptomyces coelicolor is well studied, little is still known about the role small noncoding RNAs (sRNAs) play in regulating gene expression in this organism. Here, we report the identification of a second target of the sRNA scr5239, an sRNA highly conserved in streptomycetes. The 159 nt long sRNA binds its target, the mRNA of the cobalamin independent methionine synthase metE (SCO0985), at the 5' ...

  3. Systems integration of biodefense omics data for analysis of pathogen-host interactions and identification of potential targets.

    Directory of Open Access Journals (Sweden)

    Peter B McGarvey

    Full Text Available The NIAID (National Institute for Allergy and Infectious Diseases Biodefense Proteomics program aims to identify targets for potential vaccines, therapeutics, and diagnostics for agents of concern in bioterrorism, including bacterial, parasitic, and viral pathogens. The program includes seven Proteomics Research Centers, generating diverse types of pathogen-host data, including mass spectrometry, microarray transcriptional profiles, protein interactions, protein structures and biological reagents. The Biodefense Resource Center (www.proteomicsresource.org has developed a bioinformatics framework, employing a protein-centric approach to integrate and support mining and analysis of the large and heterogeneous data. Underlying this approach is a data warehouse with comprehensive protein + gene identifier and name mappings and annotations extracted from over 100 molecular databases. Value-added annotations are provided for key proteins from experimental findings using controlled vocabulary. The availability of pathogen and host omics data in an integrated framework allows global analysis of the data and comparisons across different experiments and organisms, as illustrated in several case studies presented here. (1 The identification of a hypothetical protein with differential gene and protein expressions in two host systems (mouse macrophage and human HeLa cells infected by different bacterial (Bacillus anthracis and Salmonella typhimurium and viral (orthopox pathogens suggesting that this protein can be prioritized for additional analysis and functional characterization. (2 The analysis of a vaccinia-human protein interaction network supplemented with protein accumulation levels led to the identification of human Keratin, type II cytoskeletal 4 protein as a potential therapeutic target. (3 Comparison of complete genomes from pathogenic variants coupled with experimental information on complete proteomes allowed the identification and

  4. Genome-wide identification of microRNA targets in the neglected disease pathogens of the genus Echinococcus.

    Science.gov (United States)

    Macchiaroli, Natalia; Maldonado, Lucas L; Zarowiecki, Magdalena; Cucher, Marcela; Gismondi, María Inés; Kamenetzky, Laura; Rosenzvit, Mara Cecilia

    2017-06-01

    MicroRNAs (miRNAs), a class of small non-coding RNAs, are key regulators of gene expression at post-transcriptional level and play essential roles in biological processes such as development. MiRNAs silence target mRNAs by binding to complementary sequences in the 3'untranslated regions (3'UTRs). The parasitic helminths of the genus Echinococcus are the causative agents of echinococcosis, a zoonotic neglected disease. In previous work, we performed a comprehensive identification and characterization of Echinococcus miRNAs. However, current knowledge about their targets is limited. Since target prediction algorithms rely on complementarity between 3'UTRs and miRNA sequences, a major limitation is the lack of accurate sequence information of 3'UTR for most species including parasitic helminths. We performed RNA-seq and developed a pipeline that integrates the transcriptomic data with available genomic data of this parasite in order to identify 3'UTRs of Echinococcus canadensis. The high confidence set of 3'UTRs obtained allowed the prediction of miRNA targets in Echinococcus through a bioinformatic approach. We performed for the first time a comparative analysis of miRNA targets in Echinococcus and Taenia. We found that many evolutionarily conserved target sites in Echinococcus and Taenia may be functional and under selective pressure. Signaling pathways such as MAPK and Wnt were among the most represented pathways indicating miRNA roles in parasite growth and development. Genome-wide identification and characterization of miRNA target genes in Echinococcus provide valuable information to guide experimental studies in order to understand miRNA functions in the parasites biology. miRNAs involved in essential functions, especially those being absent in the host or showing sequence divergence with respect to host orthologs, might be considered as novel therapeutic targets for echinococcosis control. Copyright © 2017 Elsevier B.V. All rights reserved.

  5. Genome-wide identification of targets and function of individual MicroRNAs in mouse embryonic stem cells.

    Directory of Open Access Journals (Sweden)

    Sophie A Hanina

    2010-10-01

    Full Text Available Mouse Embryonic Stem (ES cells express a unique set of microRNAs (miRNAs, the miR-290-295 cluster. To elucidate the role of these miRNAs and how they integrate into the ES cell regulatory network requires identification of their direct regulatory targets. The difficulty, however, arises from the limited complementarity of metazoan miRNAs to their targets, with the interaction requiring as few as six nucleotides of the miRNA seed sequence. To identify miR-294 targets, we used Dicer1-null ES cells, which lack all endogenous mature miRNAs, and introduced just miR-294 into these ES cells. We then employed two approaches to discover miR-294 targets in mouse ES cells: transcriptome profiling using microarrays and a biochemical approach to isolate mRNA targets associated with the Argonaute2 (Ago2 protein of the RISC (RNA Induced Silencing Complex effector, followed by RNA-sequencing. In the absence of Dicer1, the RISC complexes are largely devoid of mature miRNAs and should therefore contain only transfected miR-294 and its base-paired targets. Our data suggest that miR-294 may promote pluripotency by regulating a subset of c-Myc target genes and upregulating pluripotency-associated genes such as Lin28.

  6. Transmit Energy Efficiency of Two Cognitive Radar Platforms for Target Identification

    Directory of Open Access Journals (Sweden)

    Ric Romero

    2015-06-01

    Full Text Available Cognitive radar (CRr is a recent radar paradigm that can potentially help drive aerospace innovation forward. Two specific platforms of cognitive radar used for target identification are discussed. One uses sequential hypothesis testing (SHT in the receiver processing and is referred to as SHT-CRr and the other one uses maximum a posteriori (MAP and is referred to as MAP-CRr. Our main goal in this article is to make a practical comparison between SHT-CRr and MAP-CRr platforms in terms of transmission energy efficiency. Since the performance metric for the SHT-CRr is the average number of illuminations (ANI and the performance metric for MAP-CRr is the percentage of correct decisions (\\(P_{cd}\\, a direct comparison between the platforms is difficult to perform. In this work, we introduce a useful procedure that involves a metric called total transmit energy (TTE given a fixed \\(P_{cd}\\ as a metric to measure the transmit energy efficiency of both platforms. Lower TTE means that the platform is more efficient in achieving a desired \\(P_{cd}\\. To facilitate a robust comparison, a transmit-adaptive waveform that consistently outperforms the pulsed waveform in terms of both \\(P_{cd}\\ and ANI is needed. We show that a certain adaptive waveform called the probability weighted energy signal-to-noise ratio-based (PWE-SNR waveform outperforms the pulsed wideband waveform (i.e., flat frequency response in terms of ANI and \\(P_{cd}\\ for all ranges of transmit waveform energy. We also note that the \\(P_{cd}\\ performance of SHT-CRr can be drastically different from the probability threshold (i.e., the probability value that is used to stop radar illumination for the purposes of classification, which is critically important for CRr system designers to realize. Indeed, this fact turns out to be key in accomplishing our goal to compare SHT-CRr and MAP-CRr in terms of transmit energy efficiency.

  7. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis.

    Science.gov (United States)

    Vashisht, Shikha; Bagler, Ganesh

    2012-01-01

    Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC) is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.

  8. An approach for the identification of targets specific to bone metastasis using cancer genes interactome and gene ontology analysis.

    Directory of Open Access Journals (Sweden)

    Shikha Vashisht

    Full Text Available Metastasis is one of the most enigmatic aspects of cancer pathogenesis and is a major cause of cancer-associated mortality. Secondary bone cancer (SBC is a complex disease caused by metastasis of tumor cells from their primary site and is characterized by intricate interplay of molecular interactions. Identification of targets for multifactorial diseases such as SBC, the most frequent complication of breast and prostate cancers, is a challenge. Towards achieving our aim of identification of targets specific to SBC, we constructed a 'Cancer Genes Network', a representative protein interactome of cancer genes. Using graph theoretical methods, we obtained a set of key genes that are relevant for generic mechanisms of cancers and have a role in biological essentiality. We also compiled a curated dataset of 391 SBC genes from published literature which serves as a basis of ontological correlates of secondary bone cancer. Building on these results, we implement a strategy based on generic cancer genes, SBC genes and gene ontology enrichment method, to obtain a set of targets that are specific to bone metastasis. Through this study, we present an approach for probing one of the major complications in cancers, namely, metastasis. The results on genes that play generic roles in cancer phenotype, obtained by network analysis of 'Cancer Genes Network', have broader implications in understanding the role of molecular regulators in mechanisms of cancers. Specifically, our study provides a set of potential targets that are of ontological and regulatory relevance to secondary bone cancer.

  9. Ground Wars

    DEFF Research Database (Denmark)

    Nielsen, Rasmus Kleis

    Political campaigns today are won or lost in the so-called ground war--the strategic deployment of teams of staffers, volunteers, and paid part-timers who work the phones and canvass block by block, house by house, voter by voter. Ground Wars provides an in-depth ethnographic portrait of two...... infrastructures that utilize large databases with detailed individual-level information for targeting voters, and armies of dedicated volunteers and paid part-timers. Nielsen challenges the notion that political communication in America must be tightly scripted, controlled, and conducted by a select coterie...... of professionals. Yet he also quashes the romantic idea that canvassing is a purer form of grassroots politics. In today's political ground wars, Nielsen demonstrates, even the most ordinary-seeming volunteer knocking at your door is backed up by high-tech targeting technologies and party expertise. Ground Wars...

  10. Putative drug and vaccine target protein identification using comparative genomic analysis of KEGG annotated metabolic pathways of Mycoplasma hyopneumoniae.

    Science.gov (United States)

    Damte, Dereje; Suh, Joo-Won; Lee, Seung-Jin; Yohannes, Sileshi Belew; Hossain, Md Akil; Park, Seung-Chun

    2013-07-01

    In the present study, a computational comparative and subtractive genomic/proteomic analysis aimed at the identification of putative therapeutic target and vaccine candidate proteins from Kyoto Encyclopedia of Genes and Genomes (KEGG) annotated metabolic pathways of Mycoplasma hyopneumoniae was performed for drug design and vaccine production pipelines against M.hyopneumoniae. The employed comparative genomic and metabolic pathway analysis with a predefined computational systemic workflow extracted a total of 41 annotated metabolic pathways from KEGG among which five were unique to M. hyopneumoniae. A total of 234 proteins were identified to be involved in these metabolic pathways. Although 125 non homologous and predicted essential proteins were found from the total that could serve as potential drug targets and vaccine candidates, additional prioritizing parameters characterize 21 proteins as vaccine candidate while druggability of each of the identified proteins evaluated by the DrugBank database prioritized 42 proteins suitable for drug targets. Copyright © 2013 Elsevier Inc. All rights reserved.

  11. Identification of target genes of transcription factor CEBPB in acute promyelocytic leukemia cells induced by all-trans retinoic acid

    Institute of Scientific and Technical Information of China (English)

    Lei Yu; Yang-De Zhang; Jun Zhou; De-Ming Yao; Xiang Li

    2013-01-01

    Objective: To indentify target genes of transcription factor CCAAT enhancer-binding proteinβ (CEBPB) in acute promyelocytic leukemia cells induced by all-trans retinoic acid. Methods:A new strategy for high-throughput identification of direct target genes was established by combining chromatin immunoprecipitation (ChIP) with in vitro selection. Then, 106 potential CEBPB binding fragments from the genome of the all-trans retinoic acid (ATRA)-treated NB4 cells were identified. Results: Of them, 82 were mapped in proximity to known or previously predicted genes; 7 were randomly picked up for further confirmation by ChIP-PCR and 3 genes (GALM, ITPR2 and ORM2) were found to be specifically up-regulated in the ATRA-treated NB4 cells, indicating that they might be the down-stream target genes of ATRA. Conclusions: Our results provided new insight into the mechanisms of ATRA-induced granulocytic differentiation.

  12. Identification of metE as a second target of the sRNA scr5239 in Streptomyces coelicolor.

    Directory of Open Access Journals (Sweden)

    Michael-Paul Vockenhuber

    Full Text Available While transcriptional regulation of the primary and secondary metabolism of the model organism Streptomyces coelicolor is well studied, little is still known about the role small noncoding RNAs (sRNAs play in regulating gene expression in this organism. Here, we report the identification of a second target of the sRNA scr5239, an sRNA highly conserved in streptomycetes. The 159 nt long sRNA binds its target, the mRNA of the cobalamin independent methionine synthase metE (SCO0985, at the 5' end of its open reading frame thereby repressing translation. We show that a high methionine level induces expression of scr5239 itself. This leads, in a negative feedback loop, to the repression of methionine biosynthesis. In contrast to the first reported target of this sRNA, the agarase dagA, this interaction seems to be conserved in a wide number of streptomycetes.

  13. Identification of metE as a second target of the sRNA scr5239 in Streptomyces coelicolor.

    Science.gov (United States)

    Vockenhuber, Michael-Paul; Heueis, Nona; Suess, Beatrix

    2015-01-01

    While transcriptional regulation of the primary and secondary metabolism of the model organism Streptomyces coelicolor is well studied, little is still known about the role small noncoding RNAs (sRNAs) play in regulating gene expression in this organism. Here, we report the identification of a second target of the sRNA scr5239, an sRNA highly conserved in streptomycetes. The 159 nt long sRNA binds its target, the mRNA of the cobalamin independent methionine synthase metE (SCO0985), at the 5' end of its open reading frame thereby repressing translation. We show that a high methionine level induces expression of scr5239 itself. This leads, in a negative feedback loop, to the repression of methionine biosynthesis. In contrast to the first reported target of this sRNA, the agarase dagA, this interaction seems to be conserved in a wide number of streptomycetes.

  14. Cos-Seq for high-throughput identification of drug target and resistance mechanisms in the protozoan parasite Leishmania.

    Science.gov (United States)

    Gazanion, Élodie; Fernández-Prada, Christopher; Papadopoulou, Barbara; Leprohon, Philippe; Ouellette, Marc

    2016-05-24

    Innovative strategies are needed to accelerate the identification of antimicrobial drug targets and resistance mechanisms. Here we develop a sensitive method, which we term Cosmid Sequencing (or "Cos-Seq"), based on functional cloning coupled to next-generation sequencing. Cos-Seq identified >60 loci in the Leishmania genome that were enriched via drug selection with methotrexate and five major antileishmanials (antimony, miltefosine, paromomycin, amphotericin B, and pentamidine). Functional validation highlighted both known and previously unidentified drug targets and resistance genes, including novel roles for phosphatases in resistance to methotrexate and antimony, for ergosterol and phospholipid metabolism genes in resistance to miltefosine, and for hypothetical proteins in resistance to paromomycin, amphothericin B, and pentamidine. Several genes/loci were also found to confer resistance to two or more antileishmanials. This screening method will expedite the discovery of drug targets and resistance mechanisms and is easily adaptable to other microorganisms.

  15. Computerized identification and classification of stance phases as made by front or hind feet of walking cows based on 3-dimensional ground reaction forces

    DEFF Research Database (Denmark)

    Skjøth, Flemming; Thorup, V. M.; do Nascimento, Omar Feix

    2013-01-01

    Lameness is a frequent disorder in dairy cows and in large dairy herds manual lameness detection is a time-consuming task. This study describes a method for automatic identification of stance phases in walking cows, and their classification as made by a front or a hind foot based on ground reaction...... force information. Features were derived from measurements made using two parallel 3-dimensional force plates. The approach presented is based on clustering of Centre of Pressure (COP) trace points over space and time, combined with logical sequencing of stance phases based on the dynamics...

  16. Feature Abstracting and Identification of Acoustic Target in the Battle Field Based on EMD

    Institute of Scientific and Technical Information of China (English)

    CAI Shao-chuan; ZHANG Guo-wei

    2007-01-01

    The method of empirical mode decomposition(EMD) was used for the signal processing and feature abstracting of acoustic target of battle field.According to the signal's characteristics of different targets, some feature vectors in token of the target properties were constructed and abstracted.In the basis of feature abstracting and statistic analysis for large amount of sample signal of the targets, using the maximum subjection classification method based on the fuzzy synthesis judgment, the three typical acoustic target helicopter, tank and traffic vehicle were recognized.

  17. Midlatitude Ice-Rich Ground on Mars: An Important Target for Science and In Situ Resource Utilization on Human Missions

    Science.gov (United States)

    Stoker, Carol; Heldmann, Jennifer

    2015-01-01

    The region of ROI is characterized by proven presence of near surface ground ice and numerous periglacial features. Midlatitude ground ice on Mars is of significant scientific interest for understanding the history and evolution of ice stability on Mars, the impact that changes in insolation produced by variations in Mars’ orbital parameters has on the regions climate, and could provide human exploration with a reliable and plentiful in situ resource. For both science and exploration, assessing the astrobiological potential of the ice is important in terms of (1) understanding the potential for life on Mars and (2) evaluating the presence of possible biohazards in advance of human exploration. Heldmann et al. (2014) studied locations on Mars in the Amazonis Planitia region where near surface ground ice was exposed by new impact craters (Byrne et al. 2009). The study examined whether sites in this region were suitable for human exploration including reviewing the evidence for midlatitude ground ice, discussing the possible explanations for its occurrence, assessing its potential habitability for modern life, and evaluating the resource potential. They systematically analyzed remote-sensing data sets to identify a viable landing site. Five sites where ground ice was exposed were examined with HiRise imaging and were classified according to (1) presence of polygons as a proxy for subsurface ice, (2) presence and abundance of rough topographic obstacles (e.g., large cracks, cliffs, uneven topography), (3) rock density, (4) presence and abundance of large boulders, and (5) presence of craters. A suitable landing site was found having ground ice at only 0.15m depth, and no landing site hazards within a 25 km landing ellipse. This paper presents results of that study and examines the relevance of this ROI to the workshop goals.

  18. Infrared small target's detection and identification with moving platform based on motion features

    Science.gov (United States)

    Jia, Yan; Zou, Xu; Zhong, Sheng; Lu, Hongqiang

    2015-10-01

    The infrared small target's detection and tracking are important parts of the automatic target recognition. When the camera platform equipped with an infrared camera moves, the small target's position change in the imaging plane is affected by the composite motion of the small target and the camera platform. Traditional detection and tracking algorithms may lose the small target and make the follow-up detection and tracking fail because of not considering the camera platform's movement. Moreover, when there exist small targets with different motion features in the camera's view, some detection and tracking algorithms can't recognize different targets based on their motion features because there are no trajectories in a unified coordinate system, which may lead to the true small targets undetected or detected incorrectly . To solve those problems, we present a method under the condition of moving camera platform. Firstly, get the camera platform's motion information from the inertial measurement values, and then decouple to remove the motion of the camera platform itself by means of coordinate transformation. Next, estimate the trajectories of the small targets with different motion features based on their position changes in the same imaging plane coordinate system. Finally, recognize different small targets preliminarily based on their different trajectories. Experimental results show that this method can improve the small target's detection probability. Furthermore, when the camera platform fails to track the small target, it's possible to predict the position of the small target in the next frame based on the fitted motion equation and realize sustained and stable tracking.

  19. REAL TIME PCR IDENTIFICATION FOR TARGET ADJUNCTIVE ANTIBIOTIC THERAPY OF SEVERE CHRONIC PERIODONTITIS. PART I - CLINICAL RESULTS.

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2014-10-01

    Full Text Available INTRODUCTION: The periodontal pathology is of great social importance due to the vast distribution in the human population. The adjunctive antibiotic administration could improve the healing in such cases but the latest data of the continuingly growing antibiotic resistance requires more precise approaches of antibiotic selection. The contemporary molecular diagnostic methods could offer the required precision for the microbiological identification in order to achieve better control of the periodontitis. OBJECTIVE: The aim of this study is to compare the microbiological effectiveness of adjunctive antibiotic administration with the mechanical periodontal therapy. METHODS: 30 patients with severe chronic periodontitis were enrolled in this study and were divided in 3 groups: Control group – with mechanical debridement only. Test group 1 – with combined adjunctive antibiotic administration using Amoxicillin+ Metronidazole. Test group 2 – with target antibiotic administration according to the resuts from the Real Time PCR identification. RESULTS: A considerable improvement of the periodontal status was reported in all treatment groups. The most positive results were in the group with target antibiotic administration were all tested clinical parameters showed the best improvement with statistically significant changes in sites with PD7mm and CAL>5mm. CONCLUSION: The adjunctive antibiotic administration demonstrates better clinical effectiveness concerning the reduction of the severely affected sites in cases with severe generalized chronic periodontitis compared to the mechanical therapy alone. From all examined groups the target approach has statistically significant better results. These results suggest that this approach is recommended in cases with high prevalence of deep pockets.

  20. Genome-wide identification of novel microRNAs and their target genes in the human parasite Schistosoma mansoni.

    Science.gov (United States)

    de Souza Gomes, Matheus; Muniyappa, Mohan Kumar; Carvalho, Sávio Gonçalves; Guerra-Sá, Renata; Spillane, Charles

    2011-08-01

    Mature microRNAs (miRNAs) are small, non-coding regulatory RNAs which can elicit post-transcriptional repression of mRNA levels of target genes. Here, we report the identification of 67 mature and 42 precursor miRNAs in the Schistosoma mansoni parasite. The evolutionarily conserved S. mansoni miRNAs consisted of 26 precursor miRNAs and 35 mature miRNAs, while we identified 16 precursor miRNAs and 32 mature miRNAs that displayed no conservation. These S. mansoni miRNAs are located on seven autosomal chromosomes and a sex (W) chromosome. miRNA expansion through gene duplication was suggested for at least two miRNA families miR-71 and mir-2. miRNA target finding analysis identified 389 predicted mRNA targets for the identified miRNAs and suggests that the sma-mir-71 may be involved in female sexual maturation. Given the important roles of miRNAs in animals, the identification and characterization of miRNAs in S. mansoni will facilitate novel approaches towards prevention and treatment of Schistosomiasis.

  1. Comparative genomics study for identification of putative drug targets in Salmonella typhi Ty2.

    Science.gov (United States)

    Batool, Nisha; Waqar, Maleeha; Batool, Sidra

    2016-01-15

    Typhoid presents a major health concern in developing countries with an estimated annual infection rate of 21 million. The disease is caused by Salmonella typhi, a pathogenic bacterium acquiring multiple drug resistance. We aim to identify proteins that could prove to be putative drug targets in the genome of S. typhi str. Ty2. We employed comparative and subtractive genomics to identify targets that are absent in humans and are essential to S. typhi Ty2. We concluded that 46 proteins essential to pathogen are absent in the host genome. Filtration on the basis of drug target prioritization singled out 20 potentially therapeutic targets. Their absence in the host and specificity to S. typhi Ty2 makes them ideal targets for treating typhoid in Homo sapiens. 3D structures of two of the final target enzymes, MurA and MurB have been predicted via homology modeling which are then used for a docking study.

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

    Directory of Open Access Journals (Sweden)

    Robert Duncan

    2011-01-01

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

  3. TARGET:?

    National Research Council Canada - National Science Library

    James M Acton

    2014-01-01

      By 2003. as military planners had become worried that the country's long-range conventional weapons, such as cruise missiles, might be too slow to reach hypothetical distant targets that needed to be struck urgently...

  4. Treponema pallidum putative novel drug target identification and validation: rethinking syphilis therapeutics with plant-derived terpenoids.

    Science.gov (United States)

    Dwivedi, Upendra N; Tiwari, Sameeksha; Singh, Priyanka; Singh, Swati; Awasthi, Manika; Pandey, Veda P

    2015-02-01

    Syphilis, a slow progressive and the third most common sexually transmitted disease found worldwide, is caused by a spirochete gram negative bacteria Treponema pallidum. Emergence of antibiotic resistant T. pallidum has led to a search for novel drugs and their targets. Subtractive genomics analyses of pathogen T. pallidum and host Homo sapiens resulted in identification of 126 proteins essential for survival and viability of the pathogen. Metabolic pathway analyses of these essential proteins led to discovery of nineteen proteins distributed among six metabolic pathways unique to T. pallidum. One hundred plant-derived terpenoids, as potential therapeutic molecules against T. pallidum, were screened for their drug likeness and ADMET (absorption, distribution, metabolism, and toxicity) properties. Subsequently the resulting nine terpenoids were docked with five unique T. pallidum targets through molecular modeling approaches. Out of five targets analyzed, D-alanine:D-alanine ligase was found to be the most promising target, while terpenoid salvicine was the most potent inhibitor. A comparison of the inhibitory potential of the best docked readily available natural compound, namely pomiferin (flavonoid) with that of the best docked terpenoid salvicine, revealed that salvicine was a more potent inhibitor than that of pomiferin. To the best of our knowledge, this is the first report of a terpenoid as a potential therapeutic molecule against T. pallidum with D-alanine:D-alanine ligase as a novel target. Further studies are warranted to evaluate and explore the potential clinical ramifications of these findings in relation to syphilis that has public health importance worldwide.

  5. Context-specific microRNA analysis: identification of functional microRNAs and their mRNA targets.

    Science.gov (United States)

    Bossel Ben-Moshe, Noa; Avraham, Roi; Kedmi, Merav; Zeisel, Amit; Yitzhaky, Assif; Yarden, Yosef; Domany, Eytan

    2012-11-01

    MicroRNAs (miRs) function primarily as post-transcriptional negative regulators of gene expression through binding to their mRNA targets. Reliable prediction of a miR's targets is a considerable bioinformatic challenge of great importance for inferring the miR's function. Sequence-based prediction algorithms have high false-positive rates, are not in agreement, and are not biological context specific. Here we introduce CoSMic (Context-Specific MicroRNA analysis), an algorithm that combines sequence-based prediction with miR and mRNA expression data. CoSMic differs from existing methods--it identifies miRs that play active roles in the specific biological system of interest and predicts with less false positives their functional targets. We applied CoSMic to search for miRs that regulate the migratory response of human mammary cells to epidermal growth factor (EGF) stimulation. Several such miRs, whose putative targets were significantly enriched by migration processes were identified. We tested three of these miRs experimentally, and showed that they indeed affected the migratory phenotype; we also tested three negative controls. In comparison to other algorithms CoSMic indeed filters out false positives and allows improved identification of context-specific targets. CoSMic can greatly facilitate miR research in general and, in particular, advance our understanding of individual miRs' function in a specific context.

  6. Raman and surface-enhanced Raman spectroscopy of amino acids and nucleotide bases for target bacterial vibrational mode identification

    Science.gov (United States)

    Guicheteau, Jason; Argue, Leanne; Hyre, Aaron; Jacobson, Michele; Christesen, Steven D.

    2006-05-01

    Raman and surface-enhanced Raman spectroscopy (SERS) studies of bacteria have reported a wide range of vibrational mode assignments associated with biological material. We present Raman and SER spectra of the amino acids phenylalanine, tyrosine, tryptophan, glutamine, cysteine, alanine, proline, methionine, asparagine, threonine, valine, glycine, serine, leucine, isoleucine, aspartic acid and glutamic acid and the nucleic acid bases adenosine, guanosine, thymidine, and uridine to better characterize biological vibrational mode assignments for bacterial target identification. We also report spectra of the bacteria Bacillus globigii, Pantoea agglomerans, and Yersinia rhodei along with band assignments determined from the reference spectra obtained.

  7. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions

    Energy Technology Data Exchange (ETDEWEB)

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Ansari, Nariman [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Esner, Milan; Bickle, Marc [Max Planck Institute of Molecular Cell Biology and Genetics, High-Throughput Technology Development Studio (TDS), Dresden (Germany); Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H. [Physical Biology Group, Buchmann Institute for Molecular Life Sciences (BMLS), Goethe University Frankfurt (Germany); Parczyk, Karsten; Prechtl, Stefan [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany); Steigemann, Patrick, E-mail: Patrick.Steigemann@bayer.com [Bayer Pharma AG, Global Drug Discovery, Muellerstrasse 178, 13353 Berlin (Germany)

    2014-04-15

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions. - Highlights: • Establishment of a novel method for 3D cell culture based high-content screening. • First reported high

  8. Active multispectral near-IR detection of small surface targets

    NARCIS (Netherlands)

    Jong, A.N. de; Winkel, J.; Roos, M.

    2001-01-01

    The detection and identification of small surface targets with Electro-Optical sensors is seriously hampered by ground clutter, leading to false alarms and reduced detection probabilities. Active ground illumination can improve the detection performance of EO sensors compared to passive skylight ill

  9. Chemical Genomics and Emerging DNA Technologies in the Identification of Drug Mechanisms and Drug Targets

    DEFF Research Database (Denmark)

    Olsen, Louise Cathrine Braun; Færgeman, Nils J.

    2012-01-01

    critical roles in the genomic age of biological research and drug discovery. In the present review we discuss how simple biological model organisms can be used as screening platforms in combination with emerging genomic technologies to advance the identification of potential drugs and their molecular...

  10. Identification of soybean seed developmental stage-specific and tissue-specific miRNA targets by degradome sequencing

    Directory of Open Access Journals (Sweden)

    Shamimuzzaman Md

    2012-07-01

    Full Text Available Abstract Background MicroRNAs (miRNAs regulate the expression of target genes by mediating gene silencing in both plants and animals. The miRNA targets have been extensively investigated in Arabidopsis and rice using computational prediction, experimental validation by overexpression in transgenic plants, and by degradome or PARE (parallel analysis of RNA ends sequencing. However, miRNA targets mostly remain unknown in soybean (Glycine max. More specifically miRNA mediated gene regulation at different seed developmental stages in soybean is largely unexplored. In order to dissect miRNA guided gene regulation in soybean developing seeds, we performed a transcriptome-wide experimental method using degradome sequencing to directly detect cleaved miRNA targets. Results In this study, degradome libraries were separately prepared from immature soybean cotyledons representing three stages of development and from seed coats of two stages. Sequencing and analysis of 10 to 40 million reads from each library resulted in identification of 183 different targets for 53 known soybean miRNAs. Among these, some were found only in the cotyledons representing cleavage by 25 miRNAs and others were found only in the seed coats reflecting cleavage by 12 miRNAs. A large number of targets for 16 miRNAs families were identified in both tissues irrespective of the stage. Interestingly, we identified more miRNA targets in the desiccating cotyledons of late seed maturation than in immature seed. We validated four different auxin response factor genes as targets for gma-miR160 via RNA ligase mediated 5’ rapid amplification of cDNA ends (RLM-5’RACE. Gene Ontology (GO analysis indicated the involvement of miRNA target genes in various cellular processes during seed development. Conclusions The miRNA targets in both the cotyledons and seed coats of several stages of soybean seed development have been elucidated by experimental evidence from comprehensive, high throughput

  11. A systematic identification of multiple toxin-target interactions based on chemical, genomic and toxicological data.

    Science.gov (United States)

    Zhou, Wei; Huang, Chao; Li, Yan; Duan, Jinyou; Wang, Yonghua; Yang, Ling

    2013-02-01

    Although the assessment of toxicity of various agents, -omics (genomic, proteomic, metabolomic, etc.) data has been accumulated largely, the acquirement of toxicity information of variety of molecules through experimental methods still remains a difficult task. Presently, a systems toxicology approach that integrates massive diverse chemical, genomic and toxicological information was developed for prediction of the toxin targets and their related networks. The procedures are: (1) by use of two powerful statistical methods, i.e., support vector machine (SVM) and random forest (RF), a systemic model for prediction of multiple toxin-target interactions using the extracted chemical and genomic features has been developed with its reliability and robustness estimated. And the qualitative classification of targets according to the phenotypic diseases has been taken into account to further uncover the biological meaning of the targets, as well as to validate the robustness of the in silico models. (2) Based on the predicted toxin-target interactions, a genome-scale toxin-target-disease network exampled by cardiovascular disease is generated. (3) A topological analysis of the network is carried out to identify those targets that are most susceptible in human to topical agents including the most critical toxins, as well as to uncover both the toxin-specific mechanisms and pathways. The methodologies presented herein for systems toxicology will make drug development, toxin environmental risk assessment more efficient, acceptable and cost-effective.

  12. Compensation of Cable Voltage Drops and Automatic Identification of Cable Parameters in 400 Hz Ground Power Units

    DEFF Research Database (Denmark)

    Borup, Uffe; Nielsen, Bo Vork; Blaabjerg, Frede

    2004-01-01

    In this paper a new cable voltage drop compensation scheme for ground power units (GPU) is presented. The scheme is able to predict and compensate the voltage drop in an output cable by measuring the current quantities at the source. The prediction is based on an advanced cable model that includes...

  13. Identification of Klebsiella oxytoca using a specific PCR assay targeting the polygalacturonase pehX gene.

    Science.gov (United States)

    Kovtunovych, Gennadiy; Lytvynenko, Tetyana; Negrutska, Valentyna; Lar, Olena; Brisse, Sylvain; Kozyrovska, Natalia

    2003-10-01

    Bacteria of the genus Klebsiella are important opportunistic pathogens responsible for nosocomial infections that are increasingly resistant to antimicrobial agents. Distinctive identification of the species K. oxytoca, K. pneumoniae, K. planticola, K. ornithinolytica and K. terrigena is difficult based on phenotypic tests and misidentifications are frequent in routine clinical microbiology. We developed a specific method to discriminate K. oxytoca from the other species of the genus Klebsiella, based on the PCR amplification of the polygalacturonase (pehX) gene. A PCR amplicon of 344 bp was obtained in all 35 K. oxytoca strains tested, but in none of the 29 K. pneumoniae, 12 K. planticola/K. ornithinolytica and 7 K. terrigena strains tested. The test was also negative for polygalacturonate-degrading species of the genus Erwinia. Analysis of 24 strains designated as K. pneumoniae from international collections (NCTC, PZH) revealed previous misidentification of six K. oxytoca strains. Key biochemical tests fully confirmed the pehX PCR results. The new K. oxytoca identification assay should be useful for both clinical and ecological monitoring of K. oxytoca strains, as well as for controlling the previous identification of collection strains.

  14. Non-targeted identification of prions and amyloid-forming proteins from yeast and mammalian cells.

    Science.gov (United States)

    Kryndushkin, Dmitry; Pripuzova, Natalia; Burnett, Barrington G; Shewmaker, Frank

    2013-09-20

    The formation of amyloid aggregates is implicated both as a primary cause of cellular degeneration in multiple human diseases and as a functional mechanism for providing extraordinary strength to large protein assemblies. The recent identification and characterization of several amyloid proteins from diverse organisms argues that the amyloid phenomenon is widespread in nature. Yet identifying new amyloid-forming proteins usually requires a priori knowledge of specific candidates. Amyloid fibers can resist heat, pressure, proteolysis, and denaturation by reagents such as urea or sodium dodecyl sulfate. Here we show that these properties can be exploited to identify naturally occurring amyloid-forming proteins directly from cell lysates. This proteomic-based approach utilizes a novel purification of amyloid aggregates followed by identification by mass spectrometry without the requirement for special genetic tools. We have validated this technique by blind identification of three amyloid-based yeast prions from laboratory and wild strains and disease-related polyglutamine proteins expressed in both yeast and mammalian cells. Furthermore, we found that polyglutamine aggregates specifically recruit some stress granule components, revealing a possible mechanism of toxicity. Therefore, core amyloid-forming proteins as well as strongly associated proteins can be identified directly from cells of diverse origin.

  15. Rapid plant identification using species- and group-specific primers targeting chloroplast DNA.

    Directory of Open Access Journals (Sweden)

    Corinna Wallinger

    Full Text Available Plant identification is challenging when no morphologically assignable parts are available. There is a lack of broadly applicable methods for identifying plants in this situation, for example when roots grow in mixture and for decayed or semi-digested plant material. These difficulties have also impeded the progress made in ecological disciplines such as soil- and trophic ecology. Here, a PCR-based approach is presented which allows identifying a variety of plant taxa commonly occurring in Central European agricultural land. Based on the trnT-F cpDNA region, PCR assays were developed to identify two plant families (Poaceae and Apiaceae, the genera Trifolium and Plantago, and nine plant species: Achillea millefolium, Fagopyrum esculentum, Lolium perenne, Lupinus angustifolius, Phaseolus coccineus, Sinapis alba, Taraxacum officinale, Triticum aestivum, and Zea mays. These assays allowed identification of plants based on size-specific amplicons ranging from 116 bp to 381 bp. Their specificity and sensitivity was consistently high, enabling the detection of small amounts of plant DNA, for example, in decaying plant material and in the intestine or faeces of herbivores. To increase the efficacy of identifying plant species from large number of samples, specific primers were combined in multiplex PCRs, allowing screening for multiple species within a single reaction. The molecular assays outlined here will be applicable manifold, such as for root- and leaf litter identification, botanical trace evidence, and the analysis of herbivory.

  16. Identification of thioredoxin target disulfides in proteins released from barley aleurone layers

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, J.; Yang, Fen

    2010-01-01

    Thioredoxins are ubiquitous disulfide reductases involved in a wide range of cellular processes including DNA synthesis, oxidative stress response and apoptosis. In cereal seeds thioredoxins are proposed to facilitate the germination process by reducing disulfide bonds in storage proteins and other...... targets in the starchy endosperm. Here we have applied a thiol-specific labeling approach to identify specific disulfide targets of barley thioredoxin in proteins released from barley aleurone layers incubated in buffer containing gibberellic acid....

  17. Large-scale identification of microRNA targets in murine Dgcr8-deficient embryonic stem cell lines.

    Directory of Open Access Journals (Sweden)

    Matthew P A Davis

    Full Text Available Small RNAs such as microRNAs play important roles in embryonic stem cell maintenance and differentiation. A broad range of microRNAs is expressed in embryonic stem cells while only a fraction of their targets have been identified. We have performed large-scale identification of embryonic stem cell microRNA targets using a murine embryonic stem cell line deficient in the expression of Dgcr8. These cells are heavily depleted for microRNAs, allowing us to reintroduce specific microRNA duplexes and identify refined target sets. We used deep sequencing of small RNAs, mRNA expression profiling and bioinformatics analysis of microRNA seed matches in 3' UTRs to identify target transcripts. Consequently, we have identified a network of microRNAs that converge on the regulation of several important cellular pathways. Additionally, our experiments have revealed a novel candidate for Dgcr8-independent microRNA genesis and highlighted the challenges currently facing miRNA annotation.

  18. Identification of drug targets by chemogenomic and metabolomic profiling in yeast

    KAUST Repository

    Wu, Manhong

    2012-12-01

    OBJECTIVE: To advance our understanding of disease biology, the characterization of the molecular target for clinically proven or new drugs is very important. Because of its simplicity and the availability of strains with individual deletions in all of its genes, chemogenomic profiling in yeast has been used to identify drug targets. As measurement of drug-induced changes in cellular metabolites can yield considerable information about the effects of a drug, we investigated whether combining chemogenomic and metabolomic profiling in yeast could improve the characterization of drug targets. BASIC METHODS: We used chemogenomic and metabolomic profiling in yeast to characterize the target for five drugs acting on two biologically important pathways. A novel computational method that uses a curated metabolic network was also developed, and it was used to identify the genes that are likely to be responsible for the metabolomic differences found. RESULTS AND CONCLUSION: The combination of metabolomic and chemogenomic profiling, along with data analyses carried out using a novel computational method, could robustly identify the enzymes targeted by five drugs. Moreover, this novel computational method has the potential to identify genes that are causative of metabolomic differences or drug targets. © 2012 Wolters Kluwer Health | Lippincott Williams & Wilkins.

  19. TARGETgene: a tool for identification of potential therapeutic targets in cancer.

    Directory of Open Access Journals (Sweden)

    Chia-Chin Wu

    Full Text Available The vast array of in silico resources and data of high throughput profiling currently available in life sciences research offer the possibility of aiding cancer gene and drug discovery process. Here we propose to take advantage of these resources to develop a tool, TARGETgene, for efficiently identifying mutation drivers, possible therapeutic targets, and drug candidates in cancer. The simple graphical user interface enables rapid, intuitive mapping and analysis at the systems level. Users can find, select, and explore identified target genes and compounds of interest (e.g., novel cancer genes and their enriched biological processes, and validate predictions using user-defined benchmark genes (e.g., target genes detected in RNAi screens and curated cancer genes via TARGETgene. The high-level capabilities of TARGETgene are also demonstrated through two applications in this paper. The predictions in these two applications were then satisfactorily validated by several ways, including known cancer genes, results of RNAi screens, gene function annotations, and target genes of drugs that have been used or in clinical trial in cancer treatments. TARGETgene is freely available from the Biomedical Simulations Resource web site (http://bmsr.usc.edu/Software/TARGET/TARGET.html.

  20. Computational identification of conserved microRNAs and their targets from expression sequence tags of blueberry (Vaccinium corybosum).

    Science.gov (United States)

    Li, Xuyan; Hou, Yanming; Zhang, Li; Zhang, Wenhao; Quan, Chen; Cui, Yuhai; Bian, Shaomin

    2014-06-06

    MicroRNAs (miRNAs) are a class of endogenous, approximately 21nt in length, non-coding RNA, which mediate the expression of target genes primarily at post-transcriptional levels. miRNAs play critical roles in almost all plant cellular and metabolic processes. Although numerous miRNAs have been identified in the plant kingdom, the miRNAs in blueberry, which is an economically important small fruit crop, still remain totally unknown. In this study, we reported a computational identification of miRNAs and their targets in blueberry. By conducting an EST-based comparative genomics approach, 9 potential vco-miRNAs were discovered from 22,402 blueberry ESTs according to a series of filtering criteria, designated as vco-miR156-5p, vco-miR156-3p, vco-miR1436, vco-miR1522, vco-miR4495, vco-miR5120, vco-miR5658, vco-miR5783, and vco-miR5986. Based on sequence complementarity between miRNA and its target transcript, 34 target ESTs from blueberry and 70 targets from other species were identified for the vco-miRNAs. The targets were found to be involved in transcription, RNA splicing and binding, DNA duplication, signal transduction, transport and trafficking, stress response, as well as synthesis and metabolic process. These findings will greatly contribute to future research in regard to functions and regulatory mechanisms of blueberry miRNAs.

  1. Identification of downstream metastasis-associated target genes regulated by LSD1 in colon cancer cells.

    Science.gov (United States)

    Chen, Jiang; Ding, Jie; Wang, Ziwei; Zhu, Jian; Wang, Xuejian; Du, Jiyi

    2017-03-21

    This study aims to identify downstream target genes regulated by lysine-specific demethylase 1 (LSD1) in colon cancer cells and investigate the molecular mechanisms of LSD1 influencing invasion and metastasis of colon cancer. We obtained the expression changes of downstream target genes regulated by small-interfering RNA-LSD1 and LSD1-overexpression via gene expression profiling in two human colon cancer cell lines. An Affymetrix Human Transcriptome Array 2.0 was used to identify differentially expressed genes (DEGs). We screened out LSD1-target gene associated with proliferation, metastasis, and invasion from DEGs via Gene Ontology and Pathway Studio. Subsequently, four key genes (CABYR, FOXF2, TLE4, and CDH1) were computationally predicted as metastasis-related LSD1-target genes. ChIp-PCR was applied after RT-PCR and Western blot validations to detect the occupancy of LSD1-target gene promoter-bound LSD1. A total of 3633 DEGs were significantly upregulated, and 4642 DEGs were downregulated in LSD1-silenced SW620 cells. A total of 4047 DEGs and 4240 DEGs were upregulated and downregulated in LSD1-overexpressed HT-29 cells, respectively. RT-PCR and Western blot validated the microarray analysis results. ChIP assay results demonstrated that LSD1 might be negative regulators for target genes CABYR and CDH1. The expression level of LSD1 is negatively correlated with mono- and dimethylation of histone H3 lysine4(H3K4) at LSD1- target gene promoter region. No significant mono-methylation and dimethylation of H3 lysine9 methylation was detected at the promoter region of CABYR and CDH1. LSD1- depletion contributed to the upregulation of CABYR and CDH1 through enhancing the dimethylation of H3K4 at the LSD1-target genes promoter. LSD1- overexpression mediated the downregulation of CABYR and CDH1expression through decreasing the mono- and dimethylation of H3K4 at LSD1-target gene promoter in colon cancer cells. CABYR and CDH1 might be potential LSD1-target genes in colon

  2. In silico multiple-targets identification for heme detoxification in the human malaria parasite Plasmodium falciparum.

    Science.gov (United States)

    Phaiphinit, Suthat; Pattaradilokrat, Sittiporn; Lursinsap, Chidchanok; Plaimas, Kitiporn

    2016-01-01

    Detoxification of hemoglobin byproducts or free heme is an essential step and considered potential targets for anti-malaria drug development. However, most of anti-malaria drugs are no longer effective due to the emergence and spread of the drug resistant malaria parasites. Therefore, it is an urgent need to identify potential new targets and even for target combinations for effective malaria drug design. In this work, we reconstructed the metabolic networks of Plasmodium falciparum and human red blood cells for the simulation of steady mass and flux flows of the parasite's metabolites under the blood environment by flux balance analysis (FBA). The integrated model, namely iPF-RBC-713, was then adjusted into two stage-specific metabolic models, which first was for the pathological stage metabolic model of the parasite when invaded the red blood cell without any treatment and second was for the treatment stage of the parasite when a drug acted by inhibiting the hemozoin formation and caused high production rate of heme toxicity. The process of identifying target combinations consisted of two main steps. Firstly, the optimal fluxes of reactions in both the pathological and treatment stages were computed and compared to determine the change of fluxes. Corresponding enzymes of the reactions with zero fluxes in the treatment stage but non-zero fluxes in the pathological stage were predicted as a preliminary list of potential targets in inhibiting heme detoxification. Secondly, the combinations of all possible targets listed in the first step were examined to search for the best promising target combinations resulting in more effective inhibition of the detoxification to kill the malaria parasites. Finally, twenty-three enzymes were identified as a preliminary list of candidate targets which mostly were in pyruvate metabolism and citrate cycle. The optimal set of multiple targets for blocking the detoxification was a set of heme ligase, adenosine transporter, myo

  3. The Location Method of Battlefield Targets Based on Ground Sensors%基于地面传感器的战场目标定位方法

    Institute of Scientific and Technical Information of China (English)

    鲍硕; 徐万里

    2016-01-01

    精确的网络节点定位是无线传感器网络各种应用和展开部署时自组网及网络管理的首要和基础条件,这就要求有很高的定位精度。战场侦察地面传感器系统中,大多使用声/震传感器结合时差定位法对地面目标进行定位,但其在近点定位效果较差,且若需在远点的测距精度达米级时,要求测时精度达纳秒级。无源红外传感器通过感知IR强度变化和方向对目标进行运动方向和数量的判别,它的测向误差在毫弧度级,理论上可采用多重采样相关定位法建立仿真模型,结果表明:基于红外传感器的地面目标定位算法对地面战场目标定位切实可行且定位精度较高。%Accurate network node localization is the most important and basic condition for the application and deployment of wireless sensor networks, which is the first and the basic condition of the network and the network management. Battlefield re-connaissance ground sensor system and are mainly used for acoustic/seismic sensors combined with TDOA location method to locate targets on the ground, but the in the near point positioning effect is poor, and if you need to in far ranging accuracy Damien level, measurement accuracy of Dana seconds level. Passive infrared sensor through perception about changes in the IR intensity and direction of target for discrimination of the direction and amount of the movement, the direction finding error in mrad level and theory using multiple sampling positioning method, the simulation model is established. The results show that:Based on infrared sensor ground target localization algorithm of ground battlefield target location is feasible and high positioning accuracy.

  4. Prediction of the effects of soil and target properties on the antipersonnel landmine detection performance of ground-penetrating radar: A Colombian case study

    Science.gov (United States)

    Lopera, Olga; Milisavljevic, Nada

    2007-09-01

    The performance of ground-penetrating (GPR) radar is determined fundamentally by the soil electromagnetic (EM) properties and the target characteristics. In this paper, we predict the effects of such properties on the antipersonnel (AP) landmine detection performance of GPR in a Colombian scenario. Firstly, we use available soil geophysical information in existing pedotransfer models to calculate soil EM properties. The latter are included in a two-dimensional (2D), finite-difference time-domain (FDTD) modeling program in conjunction with the characteristics of AP landmines to calculate the buried target reflection. The approach is applied to two soils selected among Colombian mine-affected areas, and several local improvised explosive devices (IEDs) and AP landmines are modeled as targets. The signatures from such targets buried in the selected soils are predicted, considering different conditions. Finally, we show how the GPR can contribute in detecting low- and non-metallic targets in these Colombian soils. Such a system could be quite adequate for complementing humanitarian landmine detection by metal detectors.

  5. Identification of potential target genes of ROR-alpha in THP1 and HUVEC cell lines.

    Science.gov (United States)

    Gulec, Cagri; Coban, Neslihan; Ozsait-Selcuk, Bilge; Sirma-Ekmekci, Sema; Yildirim, Ozlem; Erginel-Unaltuna, Nihan

    2017-04-01

    ROR-alpha is a nuclear receptor, activity of which can be modulated by natural or synthetic ligands. Due to its possible involvement in, and potential therapeutic target for atherosclerosis, we aimed to identify ROR-alpha target genes in monocytic and endothelial cell lines. We performed chromatin immunoprecipitation (ChIP) followed by tiling array (ChIP-on-chip) for ROR-alpha in monocytic cell line THP1 and endothelial cell line HUVEC. Following bioinformatic analysis of the array data, we tested four candidate genes in terms of dependence of their expression level on ligand-mediated ROR-alpha activity, and two of them in terms of promoter occupancy by ROR-alpha. Bioinformatic analyses of ChIP-on-chip data suggested that ROR-alpha binds to genomic regions near the transcription start site (TSS) of more than 3000 genes in THP1 and HUVEC. Potential ROR-alpha target genes in both cell types seem to be involved mainly in membrane receptor activity, signal transduction and ion transport. While SPP1 and IKBKA were shown to be direct target genes of ROR-alpha in THP1 monocytes, inflammation related gene HMOX1 and heat shock protein gene HSPA8 were shown to be potential target genes of ROR-alpha. Our results suggest that ROR-alpha may regulate signaling receptor activity, and transmembrane transport activity through its potential target genes. ROR-alpha seems also to play role in cellular sensitivity to environmental substances like arsenite and chloroprene. Although, the expression analyses have shown that synthetic ROR-alpha ligands can modulate some of potential ROR-alpha target genes, functional significance of ligand-dependent modulation of gene expression needs to be confirmed with further analyses. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Identification of attractive drug targets in neglected-disease pathogens using an in silico approach.

    Directory of Open Access Journals (Sweden)

    Gregory J Crowther

    Full Text Available BACKGROUND: The increased sequencing of pathogen genomes and the subsequent availability of genome-scale functional datasets are expected to guide the experimental work necessary for target-based drug discovery. However, a major bottleneck in this has been the difficulty of capturing and integrating relevant information in an easily accessible format for identifying and prioritizing potential targets. The open-access resource TDRtargets.org facilitates drug target prioritization for major tropical disease pathogens such as the mycobacteria Mycobacterium leprae and Mycobacterium tuberculosis; the kinetoplastid protozoans Leishmania major, Trypanosoma brucei, and Trypanosoma cruzi; the apicomplexan protozoans Plasmodium falciparum, Plasmodium vivax, and Toxoplasma gondii; and the helminths Brugia malayi and Schistosoma mansoni. METHODOLOGY/PRINCIPAL FINDINGS: Here we present strategies to prioritize pathogen proteins based on whether their properties meet criteria considered desirable in a drug target. These criteria are based upon both sequence-derived information (e.g., molecular mass and functional data on expression, essentiality, phenotypes, metabolic pathways, assayability, and druggability. This approach also highlights the fact that data for many relevant criteria are lacking in less-studied pathogens (e.g., helminths, and we demonstrate how this can be partially overcome by mapping data from homologous genes in well-studied organisms. We also show how individual users can easily upload external datasets and integrate them with existing data in TDRtargets.org to generate highly customized ranked lists of potential targets. CONCLUSIONS/SIGNIFICANCE: Using the datasets and the tools available in TDRtargets.org, we have generated illustrative lists of potential drug targets in seven tropical disease pathogens. While these lists are broadly consistent with the research community's current interest in certain specific proteins, and suggest

  7. Identification of microbial isolates from vacuum-packaged ground pork irradiated at 1 kGy. [Pseudomonas sp. ; Enterobacter sp

    Energy Technology Data Exchange (ETDEWEB)

    Ehioba, R.M.; Kraft, A.A.; Molins, R.A.; Walker, H.W.; Olson, D.G.; Subbaraman, G.; Skowronski, R.P.

    Bacterial cultures from irradiated (1 kGy) and nonirradiated, vacuum-packaged ground pork held at 5/sup 0/C were isolated and characterized over a 12-day storage period. The initial flora of the meat was composed mostly of Pseudomonas sp., and Enterobacter sp. Although the microflora of nonirradiated samples gradually shifted from Gram-negative to Gram-positive microorganisms, 76% of the isolates were characterized as Gram-negative at the onset of spoilage (9 days at 5/sup 0/C). In contrast, the irradiated ground pork microflora was mainly Gram-positive (66%) shortly after irradiation and increased to 97% after 9 days at 5/sup 0/C. A total of 720 isolates were identified to genus.

  8. Application of isothermal titration calorimetry and column chromatography for identification of biomolecular targets.

    Science.gov (United States)

    Zhou, Xingding; Kini, R Manjunatha; Sivaraman, J

    2011-02-01

    This protocol describes a method for identifying unknown target proteins from a mixture of biomolecules for a given drug or a lead compound. This method is based on a combination of chromatography and isothermal titration calorimetry (ITC) where ITC is used as a tracking tool. The first step involves the use of ITC to confirm the binding of ligand to a component in the biomolecular mixture. Subsequently, the biomolecular mixture is fractionated by chromatography, and the binding of the ligand with individual fractions (or subfractions) is verified by ITC. The iteration of chromatographic purification on the fractions combined with ITC results in identifying the target protein. This method is useful when the target protein or ligand is unknown and/or not amenable to labeling, chemical modification or immobilization. This protocol has been successfully used by our team and by others to identify both low-abundance and highly abundant target proteins present in biomolecular mixtures. With this protocol, it takes approximately 3-5 d to identify the target protein from a mixture.

  9. In-silico identification of miRNAs and their regulating target functions in Ocimum basilicum.

    Science.gov (United States)

    Singh, Noopur; Sharma, Ashok

    2014-12-01

    microRNA is known to play an important role in growth and development of the plants and also in environmental stress. Ocimum basilicum (Basil) is a well known herb for its medicinal properties. In this study, we used in-silico approaches to identify miRNAs and their targets regulating different functions in O. basilicum using EST approach. Additionally, functional annotation, gene ontology and pathway analysis of identified target transcripts were also done. Seven miRNA families were identified. Meaningful regulations of target transcript by identified miRNAs were computationally evaluated. Four miRNA families have been reported by us for the first time from the Lamiaceae. Our results further confirmed that uracil was the predominant base in the first positions of identified mature miRNA sequence, while adenine and uracil were predominant in pre-miRNA sequences. Phylogenetic analysis was carried out to determine the relation between O. basilicum and other plant pre-miRNAs. Thirteen potential targets were evaluated for 4 miRNA families. Majority of the identified target transcripts regulated by miRNAs showed response to stress. miRNA 5021 was also indicated for playing an important role in the amino acid metabolism and co-factor metabolism in this plant. To the best of our knowledge this is the first in silico study describing miRNAs and their regulation in different metabolic pathways of O. basilicum.

  10. A Therapeutic Targeting Identification from Microarray Data and Quantitative Network Analysis

    Directory of Open Access Journals (Sweden)

    Hongliang Hu

    2015-03-01

    Full Text Available Personalized therapy is “the right drug for the right patient at the right time”. Here we reported a case of personalized therapy using gene expression signature (GES related drug discovery to treat a patient with drug-resistant metastases from breast-tumor. Methods: After mRNA obtained from metastatic liver tissue was performed by microarray, GES of genomic profiles were uncovered by bioinformatics tool and targeting drugs related with GES were mined by drug-bank. Several targeting-drugs approved by FDA were selected to treat the patient. Results: 1198 genes were uncovered for the higher expression by two-fold to compare normal liver specimens in which 10 of mined genes were identified as set-1 GES for metastasis and 16 of genes were uncovered as set-2 directly for primary breast tumor. Drug-bank platform were used to discover drugs for target set-1/2 genes. Eventually, medropxyoprogesterone (MPA targeting set-I gene and doxorubicin targeting set-2 gene were selected for the patient because the two drugs have already been approved by FDA. After doxorubicin and MPA were administered, patient's metastatic-tumor showed complete response. Conclusions: We not only analyze genomic expression profiles but also discover sensitive compounds for drug-resistant tumor. We successfully select drugs approved by FDA to treat the patient.

  11. Identification of Potential Drug Targets in Cancer Signaling Pathways using Stochastic Logical Models.

    Science.gov (United States)

    Zhu, Peican; Aliabadi, Hamidreza Montazeri; Uludağ, Hasan; Han, Jie

    2016-03-18

    The investigation of vulnerable components in a signaling pathway can contribute to development of drug therapy addressing aberrations in that pathway. Here, an original signaling pathway is derived from the published literature on breast cancer models. New stochastic logical models are then developed to analyze the vulnerability of the components in multiple signalling sub-pathways involved in this signaling cascade. The computational results are consistent with the experimental results, where the selected proteins were silenced using specific siRNAs and the viability of the cells were analyzed 72 hours after silencing. The genes elF4E and NFkB are found to have nearly no effect on the relative cell viability and the genes JAK2, Stat3, S6K, JUN, FOS, Myc, and Mcl1 are effective candidates to influence the relative cell growth. The vulnerabilities of some targets such as Myc and S6K are found to vary significantly depending on the weights of the sub-pathways; this will be indicative of the chosen target to require customization for therapy. When these targets are utilized, the response of breast cancers from different patients will be highly variable because of the known heterogeneities in signaling pathways among the patients. The targets whose vulnerabilities are invariably high might be more universally acceptable targets.

  12. Identification of ground motion features for high-tech facility under far field seismic waves using wavelet packet transform

    Science.gov (United States)

    Huang, Shieh-Kung; Loh, Chin-Hsiung; Chen, Chin-Tsun

    2016-04-01

    Seismic records collected from earthquake with large magnitude and far distance may contain long period seismic waves which have small amplitude but with dominant period up to 10 sec. For a general situation, the long period seismic waves will not endanger the safety of the structural system or cause any uncomfortable for human activity. On the contrary, for those far distant earthquakes, this type of seismic waves may cause a glitch or, furthermore, breakdown to some important equipments/facilities (such as the high-precision facilities in high-tech Fab) and eventually damage the interests of company if the amplitude becomes significant. The previous study showed that the ground motion features such as time-variant dominant frequencies extracted using moving window singular spectrum analysis (MWSSA) and amplitude characteristics of long-period waves identified from slope change of ground motion Arias Intensity can efficiently indicate the damage severity to the high-precision facilities. However, embedding a large hankel matrix to extract long period seismic waves make the MWSSA become a time-consumed process. In this study, the seismic ground motion data collected from broadband seismometer network located in Taiwan were used (with epicenter distance over 1000 km). To monitor the significant long-period waves, the low frequency components of these seismic ground motion data are extracted using wavelet packet transform (WPT) to obtain wavelet coefficients and the wavelet entropy of coefficients are used to identify the amplitude characteristics of long-period waves. The proposed method is a timesaving process compared to MWSSA and can be easily implemented for real-time detection. Comparison and discussion on this method among these different seismic events and the damage severity to the high-precision facilities in high-tech Fab is made.

  13. 3D high-content screening for the identification of compounds that target cells in dormant tumor spheroid regions.

    Science.gov (United States)

    Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan; Krebs, Alice; Christian, Sven; Prinz, Florian; Osterland, Marc; Golfier, Sven; Räse, Sebastian; Ansari, Nariman; Esner, Milan; Bickle, Marc; Pampaloni, Francesco; Mattheyer, Christian; Stelzer, Ernst H; Parczyk, Karsten; Prechtl, Stefan; Steigemann, Patrick

    2014-04-15

    Cancer cells in poorly vascularized tumor regions need to adapt to an unfavorable metabolic microenvironment. As distance from supplying blood vessels increases, oxygen and nutrient concentrations decrease and cancer cells react by stopping cell cycle progression and becoming dormant. As cytostatic drugs mainly target proliferating cells, cancer cell dormancy is considered as a major resistance mechanism to this class of anti-cancer drugs. Therefore, substances that target cancer cells in poorly vascularized tumor regions have the potential to enhance cytostatic-based chemotherapy of solid tumors. With three-dimensional growth conditions, multicellular tumor spheroids (MCTS) reproduce several parameters of the tumor microenvironment, including oxygen and nutrient gradients as well as the development of dormant tumor regions. We here report the setup of a 3D cell culture compatible high-content screening system and the identification of nine substances from two commercially available drug libraries that specifically target cells in inner MCTS core regions, while cells in outer MCTS regions or in 2D cell culture remain unaffected. We elucidated the mode of action of the identified compounds as inhibitors of the respiratory chain and show that induction of cell death in inner MCTS core regions critically depends on extracellular glucose concentrations. Finally, combinational treatment with cytostatics showed increased induction of cell death in MCTS. The data presented here shows for the first time a high-content based screening setup on 3D tumor spheroids for the identification of substances that specifically induce cell death in inner tumor spheroid core regions. This validates the approach to use 3D cell culture screening systems to identify substances that would not be detectable by 2D based screening in otherwise similar culture conditions.

  14. Targeted and random mutagenesis of Ehrlichia chaffeensis for the identification of genes required for in vivo infection.

    Science.gov (United States)

    Cheng, Chuanmin; Nair, Arathy D S; Indukuri, Vijaya V; Gong, Shanzhong; Felsheim, Roderick F; Jaworski, Deborah; Munderloh, Ulrike G; Ganta, Roman R

    2013-02-01

    Ehrlichia chaffeensis is a tick transmitted pathogen responsible for the disease human monocytic ehrlichiosis. Research to elucidate gene function in rickettsial pathogens is limited by the lack of genetic manipulation methods. Mutational analysis was performed, targeting to specific and random insertion sites within the bacterium's genome. Targeted mutagenesis at six genomic locations by homologous recombination and mobile group II intron-based methods led to the consistent identification of mutants in two genes and in one intergenic site; the mutants persisted in culture for 8 days. Three independent experiments using Himar1 transposon mutagenesis of E. chaffeensis resulted in the identification of multiple mutants; these mutants grew continuously in macrophage and tick cell lines. Nine mutations were confirmed by sequence analysis. Six insertions were located within non-coding regions and three were present in the coding regions of three transcriptionally active genes. The intragenic mutations prevented transcription of all three genes. Transposon mutants containing a pool of five different insertions were assessed for their ability to infect deer and subsequent acquisition by Amblyomma americanum ticks, the natural reservoir and vector, respectively. Three of the five mutants with insertions into non-coding regions grew well in deer. Transposition into a differentially expressed hypothetical gene, Ech_0379, and at 18 nucleotides downstream to Ech_0230 gene coding sequence resulted in the inhibition of growth in deer, which is further evidenced by their failed acquisition by ticks. Similarly, a mutation into the coding region of ECH_0660 gene inhibited the in vivo growth in deer. This is the first study evaluating targeted and random mutagenesis in E. chaffeensis, and the first to report the generation of stable mutants in this obligate intracellular bacterium. We further demonstrate that in vitro mutagenesis coupled with in vivo infection assessment is a

  15. Targeted and random mutagenesis of Ehrlichia chaffeensis for the identification of genes required for in vivo infection.

    Directory of Open Access Journals (Sweden)

    Chuanmin Cheng

    2013-02-01

    Full Text Available Ehrlichia chaffeensis is a tick transmitted pathogen responsible for the disease human monocytic ehrlichiosis. Research to elucidate gene function in rickettsial pathogens is limited by the lack of genetic manipulation methods. Mutational analysis was performed, targeting to specific and random insertion sites within the bacterium's genome. Targeted mutagenesis at six genomic locations by homologous recombination and mobile group II intron-based methods led to the consistent identification of mutants in two genes and in one intergenic site; the mutants persisted in culture for 8 days. Three independent experiments using Himar1 transposon mutagenesis of E. chaffeensis resulted in the identification of multiple mutants; these mutants grew continuously in macrophage and tick cell lines. Nine mutations were confirmed by sequence analysis. Six insertions were located within non-coding regions and three were present in the coding regions of three transcriptionally active genes. The intragenic mutations prevented transcription of all three genes. Transposon mutants containing a pool of five different insertions were assessed for their ability to infect deer and subsequent acquisition by Amblyomma americanum ticks, the natural reservoir and vector, respectively. Three of the five mutants with insertions into non-coding regions grew well in deer. Transposition into a differentially expressed hypothetical gene, Ech_0379, and at 18 nucleotides downstream to Ech_0230 gene coding sequence resulted in the inhibition of growth in deer, which is further evidenced by their failed acquisition by ticks. Similarly, a mutation into the coding region of ECH_0660 gene inhibited the in vivo growth in deer. This is the first study evaluating targeted and random mutagenesis in E. chaffeensis, and the first to report the generation of stable mutants in this obligate intracellular bacterium. We further demonstrate that in vitro mutagenesis coupled with in vivo infection

  16. Identification of the Schistosoma mansoni Molecular Target for the Antimalarial Drug Artemether

    KAUST Repository

    Lepore, Rosalba

    2011-11-28

    Plasmodium falciparum and Schistosoma mansonii are the parasites responsible for most of the malaria and schistosomiasis cases in the world. Notwithstanding their many differences, the two agents have striking similarities in that they both are blood feeders and are targets of an overlapping set of drugs, including the well-known artemether molecule. Here we explore the possibility of using the known information about the mode of action of artemether in Plasmodium to identify the molecular target of the drug in Schistosoma and provide evidence that artemether binds to SmSERCA, a putative Ca2+-ATPase of Schistosoma. We also predict the putative binding mode of the molecule for both its Plasmodium and Schistosoma targets. Our analysis of the mode of binding of artemether to Ca2+-ATPases also provides an explanation for the apparent paradox that, although the molecule has no side effect in humans, it has been shown to possess antitumoral activity. © 2011 American Chemical Society.

  17. Metabolic network analysis-based identification of antimicrobial drug targets in category A bioterrorism agents.

    Science.gov (United States)

    Ahn, Yong-Yeol; Lee, Deok-Sun; Burd, Henry; Blank, William; Kapatral, Vinayak

    2014-01-01

    The 2001 anthrax mail attacks in the United States demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. Here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three Category A-designated bioterrorism agents including Bacillus anthracis, Francisella tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all strains across the three distinct genera were identified as targets. Antimicrobial agents against some of these enzymes are available. Thus, a combination of cross species-specific antibiotics and common antimicrobials against shared targets may represent a useful combinatorial therapeutic approach against all Category A bioterrorism agents.

  18. Metabolic network analysis-based identification of antimicrobial drug targets in category A bioterrorism agents.

    Directory of Open Access Journals (Sweden)

    Yong-Yeol Ahn

    Full Text Available The 2001 anthrax mail attacks in the United States demonstrated the potential threat of bioterrorism, hence driving the need to develop sophisticated treatment and diagnostic protocols to counter biological warfare. Here, by performing flux balance analyses on the fully-annotated metabolic networks of multiple, whole genome-sequenced bacterial strains, we have identified a large number of metabolic enzymes as potential drug targets for each of the three Category A-designated bioterrorism agents including Bacillus anthracis, Francisella tularensis and Yersinia pestis. Nine metabolic enzymes- belonging to the coenzyme A, folate, phosphatidyl-ethanolamine and nucleic acid pathways common to all strains across the three distinct genera were identified as targets. Antimicrobial agents against some of these enzymes are available. Thus, a combination of cross species-specific antibiotics and common antimicrobials against shared targets may represent a useful combinatorial therapeutic approach against all Category A bioterrorism agents.

  19. Identification and characterization of the mitochondrial targeting sequence and mechanism in human citrate synthase.

    Science.gov (United States)

    Cheng, Tsung-Lin; Liao, Ching-Chun; Tsai, Wen-Hui; Lin, Chin-Chih; Yeh, Chin-Wei; Teng, Chiao-Fang; Chang, Wen-Tsan

    2009-08-01

    Citrate synthase (CS), the first and rate-limiting enzyme of the tricarboxylic acid (TCA) cycle, plays a decisive role in regulating energy generation of mitochondrial respiration. Most mitochondrial proteins are synthesized in the cytoplasm as preproteins with an amino (N)-terminal mitochondrial targeting sequence (MTS) that directs mitochondria-specific sorting of the preprotein. However, the MTS and targeting mechanism of the human CS protein are not fully characterized. The human CS gene is a single nuclear gene which transcribes into two mRNA variants, isoform a (CSa) and b (CSb), by alternative splicing of exon 2. CSa encodes 466 amino acids, including a putative N-terminal MTS, while CSb expresses 400 residues with a shorter N terminus, lacking the MTS. Our results indicated that CSa is localized in the mitochondria and the N-terminal 27 amino acids, including a well-conserved RXY downward arrow (S/A) motif (the RHAS sequence), can efficiently target the enhanced green fluorescent protein (EGFP) into the mitochondria. Furthermore, site-directed mutagenesis analysis of the conserved basic amino acids and serine/threonine residues revealed that the R9 residue is essential but all serine/threonine residues are dispensable in the mitochondrial targeting function. Moreover, RNA interference (RNAi)-mediated gene silencing of the preprotein import receptors, including TOM20, TOM22, and TOM70, showed that all three preprotein import receptors are required for transporting CSa into the mitochondria. In conclusion, we have experimentally identified the mitochondrial targeting sequence of human CSa and elucidated its targeting mechanism. These results provide an important basis for the study of mitochondrial dysfunction due to aberrant CSa trafficking.

  20. Dynamics of target-mediated drug disposition: characteristic profiles and parameter identification.

    Science.gov (United States)

    Peletier, Lambertus A; Gabrielsson, Johan

    2012-10-01

    In this paper we present a mathematical analysis of the basic model for target mediated drug disposition (TMDD). Assuming high affinity of ligand to target, we give a qualitative characterisation of ligand versus time graphs for different dosing regimes and derive accurate analytic approximations of different phases in the temporal behaviour of the system. These approximations are used to estimate model parameters, give analytical approximations of such quantities as area under the ligand curve and clearance. We formulate conditions under which a suitably chosen Michaelis-Menten model provides a good approximation of the full TMDD-model over a specified time interval.

  1. Identification of new pancreatic beta cell targets for in vivo imaging by a systems biology approach.

    Science.gov (United States)

    Bouckenooghe, Thomas; Flamez, Daisy; Ortis, Fernanda; Goldman, Serge; Eizirik, Decio L

    2010-05-01

    Systems biology is an emergent field that aims to understand biological systems at system-level. The increasing power of genome sequencing techniques and ranges of other molecular biology techniques is enabling the accumulation of in-depth knowledge of biological systems. This growing information, properly quantified, analysed and presented, will eventually allow the establishment of a system-based cartography of different cellular populations within the organism, and of their interactions at the tissue and organ levels. It will also allow the identification of specific markers of individual cell types. Systems biology approaches to discover diagnostic markers may have an important role in diabetes. There are presently no reliable ways to quantify beta cell mass (BCM) in vivo, which hampers the understanding of the pathogenesis and natural history of diabetes, and the development of novel therapies to preserve BCM. To solve this problem, novel and specific beta cell biomarkers must be identified to enable adequate in vivo imaging by methods such as Positron Emission Tomography (PET). The ideal biomarker should allow measurements by a minimally invasive technology enabling repeated examinations over time, should identify the early stages of decreased BCM, and should provide information on progression of beta cell loss and eventual responses to agents aiming to arrest or revert beta cell loss in diabetes. The present review briefly describes the "state-of-the-art" in the field, and then proposes a step-by-step systems biology approach for the identification and initial testing of novel candidates for beta cell imaging.

  2. Identification of hot spots of malaria transmission for targeted malaria control.

    NARCIS (Netherlands)

    Bousema, T.; Drakeley, C.; Gesase, S.; Hashim, R.; Magesa, S.; Mosha, F.; Otieno, S.; Carneiro, I.; Cox, J.; Msuya, E.; Kleinschmidt, I.; Maxwell, C.; Greenwood, B.; Riley, E.; Sauerwein, R.W.; Chandramohan, D.; Gosling, R.

    2010-01-01

    BACKGROUND: Variation in the risk of malaria within populations is a frequently described but poorly understood phenomenon. This heterogeneity creates opportunities for targeted interventions but only if hot spots of malaria transmission can be easily identified. METHODS: We determined spatial patte

  3. Identification of SUMO Targets by a Novel Proteomic Approach in Plants

    Institute of Scientific and Technical Information of China (English)

    Gema López-Torrejón; Davide Guerra; Rafael Catalá; Julio Salinas; Juan C.del Pozo

    2013-01-01

    Post-translational modifications (PTMs) chemically and physically alter the properties of proteins,including their folding,subcellular localization,stability,activity,and consequently their function.In spite of their relevance,studies on PTMs in plants are still limited.Small Ubiquitin-like Modifier (SUMO) modification regulates several biological processes by affecting protein-protein interactions,or changing the subcellular localizations of the target proteins.Here,we describe a novel proteomic approach to identify SUMO targets that combines 2-D liquid chromatography,immunodetection,and mass spectrometry (MS) analyses.We have applied this approach to identify nuclear SUMO targets in response to heat shock.Using a bacterial SUMOylation system,we validated that some of the targets identified here are,in fact,labeled with SUMO1.Interestingly,we found that GIGANTEA (GI),a photoperiodic-pathway protein,is modified with SUMO in response to heat shock both in vitro and in vivo.

  4. Identification and characterization of DNAzymes targeting DNA methyltransferase I for suppressing bladder cancer proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Xiangbo; Zhang, Lu; Ding, Nianhua; Yang, Xinghui; Zhang, Jin; He, Jiang; Li, Zhi; Sun, Lun-Quan, E-mail: lunquansun@csu.edu.cn

    2015-05-29

    Epigenetic inactivation of genes plays a critical role in many important human diseases, especially in cancer. A core mechanism for epigenetic inactivation of the genes is methylation of CpG islands in genome DNA, which is catalyzed by DNA methyltransferases (DNMTs). The inhibition of DNMTs may lead to demethylation and expression of the silenced tumor suppressor genes. Although DNMT inhibitors are currently being developed as potential anticancer agents, only limited success is achieved due to substantial toxicity. Here, we utilized a multiplex selection system to generate efficient RNA-cleaving DNAzymes targeting DNMT1. The lead molecule from the selection was shown to possess efficient kinetic profiles and high efficiency in inhibiting the enzyme activity. Transfection of the DNAzyme caused significant down-regulation of DNMT1 expression and reactivation of p16 gene, resulting in reduced cell proliferation of bladder cancers. This study provides an alternative for targeting DNMTs for potential cancer therapy. - Highlights: • Identified DNMT1-targeted DNAzymes by multiplex selection system. • Biochemically characterized a lead DNAzyme with high kinetic efficiency. • Validated DNMT1-targeted DNAzyme in its enzymatic and cellular activities.

  5. Metabolomics as a tool for target identification in strain improvement: The influence of phenotype definition

    NARCIS (Netherlands)

    Braaksma, M.; Bijlsma, S.; Coulier, L.; Punt, P.J.; Werf, M.J. van der

    2011-01-01

    For the optimization of microbial production processes, the choice of the quantitative phenotype to be optimized is crucial. For instance, for the optimization of product formation, either product concentration or productivity can be pursued, potentially resulting in different targets for strain

  6. Metabolomics as a tool for target identification in strain improvement: The influence of phenotype definition

    NARCIS (Netherlands)

    Braaksma, M.; Bijlsma, S.; Coulier, L.; Punt, P.J.; Werf, M.J. van der

    2011-01-01

    For the optimization of microbial production processes, the choice of the quantitative phenotype to be optimized is crucial. For instance, for the optimization of product formation, either product concentration or productivity can be pursued, potentially resulting in different targets for strain imp

  7. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer

    NARCIS (Netherlands)

    Heerma van Voss, Marise R.; Vesuna, Farhad; Trumpi, Kari; Brilliant, Justin; Berlinicke, Cynthia; de Leng, Wendy; Kranenburg, OW; Offerhaus, Johan G.; Bürger, Horst; van der Wall, E.; van Diest, Paul J.; Raman, Venu

    2015-01-01

    Identifying druggable targets in the Wnt-signaling pathway can optimize colorectal cancer treatment. Recent studies have identified a member of the RNA helicase family DDX3 (DDX3X) as a multilevel activator of Wnt signaling in cells without activating mutations in the Wnt-signaling pathway. In this

  8. Global Identification of MicroRNAs and Their Targets in Barley under Salinity Stress.

    Science.gov (United States)

    Deng, Pingchuan; Wang, Le; Cui, Licao; Feng, Kewei; Liu, Fuyan; Du, Xianghong; Tong, Wei; Nie, Xiaojun; Ji, Wanquan; Weining, Song

    2015-01-01

    Salinity is a major limiting factor for agricultural production worldwide. A better understanding of the mechanisms of salinity stress response will aid efforts to improve plant salt tolerance. In this study, a combination of small RNA and mRNA degradome sequencing was used to identify salinity responsive-miRNAs and their targets in barley. A total of 152 miRNAs belonging to 126 families were identified, of which 44 were found to be salinity responsive with 30 up-regulated and 25 down-regulated respectively. The majority of the salinity-responsive miRNAs were up-regulated at the 8h time point, while down-regulated at the 3h and 27h time points. The targets of these miRNAs were further detected by degradome sequencing coupled with bioinformatics prediction. Finally, qRT-PCR was used to validate the identified miRNA and their targets. Our study systematically investigated the expression profile of miRNA and their targets in barley during salinity stress phase, which can contribute to understanding how miRNAs respond to salinity stress in barley and other cereal crops.

  9. Identification and Validation of Novel Drug Targets for the Treatment of Plasmodium falciparum Malaria : New Insights

    NARCIS (Netherlands)

    Lunev, Sergey; de Assis Batista, Fernando; Bosch, Soraya; Wrenger, Carsten; Groves, Matthew; Rodriguez-Morales, Alfonso

    2016-01-01

    In order to counter the malarial parasite’s striking ability to rapidly develop drug resistance, a constant supply of novel antimalarial drugs and potential drug targets must be available. The so-called Harlow-Knapp effect, or “searching under the lamp post,” in which scientists tend to further

  10. Genome-wide identification of structural variants in genes encoding drug targets

    DEFF Research Database (Denmark)

    Rasmussen, Henrik Berg; Dahmcke, Christina Mackeprang

    2012-01-01

    The objective of the present study was to identify structural variants of drug target-encoding genes on a genome-wide scale. We also aimed at identifying drugs that are potentially amenable for individualization of treatments based on knowledge about structural variation in the genes encoding the...

  11. A General Theory of Target Identification: An Analytical Approach to Cognition, Perception, and Knowledge

    Science.gov (United States)

    1985-05-01

    Mystics, Hegel, Kant, Kierkegaard, Marcel (The Mystery of Beina, Vols I and II), Husserl , Heidegger and a host of others. The trouble with all this activity...Torchbooks, TB/1376, 1963. 8. Huynen, J. Richard, " Phenomenological Theory of Radar Targets," Chapter 11 in Electromagnetic Scattering (P.L.E. Uslenghi

  12. Identification of conserved, centrosome-targeting ASH domains in TRAPPII complex subunits and TRAPPC8

    DEFF Research Database (Denmark)

    Schou, Kenneth Bødtker; Morthorst, Stine Kjær; Christensen, Søren Tvorup

    2014-01-01

    microscopy analysis of cultured mammalian cells revealed that exogenously expressed ASH domains, as well as endogenous TRAPPC8, localize to the centrosome/basal body. Further, depletion of TRAPPC8 impaired ciliogenesis and GFP-Rabin8 centrosome targeting. CONCLUSIONS: Our results suggest that ASH domains...

  13. Identification and characterization of a novel peptide ligand of Tie2 for targeting gene therapy

    Institute of Scientific and Technical Information of China (English)

    Xianghua Wu; Jianren Gu; Zonghai Li; Ming Yao; Huamao Wang; Sumin Qu; Xianlian Chen; Jinjun Li; Ye Sun; Yuhong Xu

    2008-01-01

    Tyrosine kinase with immunoglobulin and epidermal growth factor homology domain-2 (Tie2) has been considered as a rational target for gene therapy in solid tumors. In order to identify a novel peptide ligand of Tie2 for targeted gene therapy, we screened a phage display peptide library and identified a candidate peptide ligand NSLSNASEFRAPY(designated GA5).Binding assays and Scatchard analysis revealed that GA5 could specifically bind to Tie2 with a dissociation constant of 2.1×10-8M.In addition,we showed that GA5 was internalized into tumor cells highly expressing Tie2.In the biodistribution assay.125I-GA5 was mainly accumniated in SPC-A1 xenograft tumors that express Tie2.Ingene delivery studies,GA5-conjugated polyethylenimine vector could achieve greater transgene transduction than non-targeted vectors both in vitro and in vivo.Tumor growth inhibition was observed in SPC-A1 xenograft-bearing mice that received eight intratumoral injections of GA5 polyethylenimine/p53 complexes in 3 weeks.The difference in tumor volume between the experiment and control groups was significant(P<0.05).Our results showed that GA5 is a potentially efficient targeting element for cancer gene or molecular therapy.

  14. Identification and Regulation of c-Myb Target Genes in MCF-7 Cells

    Directory of Open Access Journals (Sweden)

    O'Rourke John P

    2011-01-01

    Full Text Available Abstract Background The c-Myb transcription factor regulates differentiation and proliferation in hematopoietic cells, stem cells and epithelial cells. Although oncogenic versions of c-Myb were first associated with leukemias, over expression or rearrangement of the c-myb gene is common in several types of solid tumors, including breast cancers. Expression of the c-myb gene in human breast cancer cells is dependent on estrogen stimulation, but little is known about the activities of the c-Myb protein or what genes it regulates in estrogen-stimulated cells. Methods We used chromatin immunoprecipitation coupled with whole genome promoter tiling microarrays to identify endogenous c-Myb target genes in human MCF-7 breast cancer cells and characterized the activity of c-Myb at a panel of target genes during different stages of estrogen deprivation and stimulation. Results By using different antibodies and different growth conditions, the c-Myb protein was found associated with over 10,000 promoters in MCF-7 cells, including many genes that encode cell cycle regulators or transcription factors and more than 60 genes that encode microRNAs. Several previously identified c-Myb target genes were identified, including CCNB1, MYC and CXCR4 and novel targets such as JUN, KLF4, NANOG and SND1. By studying a panel of these targets to validate the results, we found that estradiol stimulation triggered the association of c-Myb with promoters and that association correlated with increased target gene expression. We studied one target gene, CXCR4, in detail, showing that c-Myb associated with the CXCR4 gene promoter and activated a CXCR4 reporter gene in transfection assays. Conclusions Our results show that c-Myb associates with a surprisingly large number of promoters in human cells. The results also suggest that estradiol stimulation leads to large-scale, genome-wide changes in c-Myb activity and subsequent changes in gene expression in human breast cancer

  15. Identification of novel endogenous antisense transcripts by DNA microarray analysis targeting complementary strand of annotated genes

    Directory of Open Access Journals (Sweden)

    Kohama Chihiro

    2009-08-01

    Full Text Available Abstract Background Recent transcriptomic analyses in mammals have uncovered the widespread occurrence of endogenous antisense transcripts, termed natural antisense transcripts (NATs. NATs are transcribed from the opposite strand of the gene locus and are thought to control sense gene expression, but the mechanism of such regulation is as yet unknown. Although several thousand potential sense-antisense pairs have been identified in mammals, examples of functionally characterized NATs remain limited. To identify NAT candidates suitable for further functional analyses, we performed DNA microarray-based NAT screening using mouse adult normal tissues and mammary tumors to target not only the sense orientation but also the complementary strand of the annotated genes. Results First, we designed microarray probes to target the complementary strand of genes for which an antisense counterpart had been identified only in human public cDNA sources, but not in the mouse. We observed a prominent expression signal from 66.1% of 635 target genes, and 58 genes of these showed tissue-specific expression. Expression analyses of selected examples (Acaa1b and Aard confirmed their dynamic transcription in vivo. Although interspecies conservation of NAT expression was previously investigated by the presence of cDNA sources in both species, our results suggest that there are more examples of human-mouse conserved NATs that could not be identified by cDNA sources. We also designed probes to target the complementary strand of well-characterized genes, including oncogenes, and compared the expression of these genes between mammary cancerous tissues and non-pathological tissues. We found that antisense expression of 95 genes of 404 well-annotated genes was markedly altered in tumor tissue compared with that in normal tissue and that 19 of these genes also exhibited changes in sense gene expression. These results highlight the importance of NAT expression in the regulation

  16. Identification of the Ki-1 antigen (CD30) as a novel therapeutic target in systemic mastocytosis.

    Science.gov (United States)

    Blatt, Katharina; Cerny-Reiterer, Sabine; Schwaab, Juliana; Sotlar, Karl; Eisenwort, Gregor; Stefanzl, Gabriele; Hoermann, Gregor; Mayerhofer, Matthias; Schneeweiss, Mathias; Knapp, Sylvia; Rülicke, Thomas; Hadzijusufovic, Emir; Bauer, Karin; Smiljkovic, Dubravka; Willmann, Michael; Reiter, Andreas; Horny, Hans-Peter; Valent, Peter

    2015-12-24

    The Ki-1 antigen (CD30) is an established therapeutic target in patients with Hodgkin lymphoma and anaplastic large-cell lymphoma. We have recently shown that CD30 is expressed abundantly in the cytoplasm of neoplastic mast cells (MCs) in patients with advanced systemic mastocytosis (SM). In the current study, we asked whether CD30 is expressed on the surface of neoplastic MCs in advanced SM, and whether this surface structure may serve as therapeutic target in SM. As assessed by flow cytometry, CD30 was found to be expressed on the surface of neoplastic MCs in 3 of 25 patients (12%) with indolent SM, 4 of 7 patients (57%) with aggressive SM, and 4 of 7 patients (57%) with MC leukemia. The immature RAS-transformed human MC line MCPV-1.1 also expressed cell surface CD30, whereas the KIT-transformed MC line HMC-1.2 expressed no detectable CD30. The CD30-targeting antibody-conjugate brentuximab-vedotin inhibited proliferation in neoplastic MCs, with lower IC50 values obtained in CD30(+) MCPV-1.1 cells (10 µg/mL) compared with CD30(-) HMC-1.2 cells (>50 µg/mL). In addition, brentuximab-vedotin suppressed the engraftment of MCPV-1.1 cells in NSG mice. Moreover, brentuximab-vedotin produced apoptosis in all CD30(+) MC lines tested as well as in primary neoplastic MCs in patients with CD30(+) SM, but did not induce apoptosis in neoplastic MCs in patients with CD30(-) SM. Furthermore, brentuximab-vedotin was found to downregulate anti-IgE-induced histamine release in CD30(+) MCs. Finally, brentuximab-vedotin and the KIT D816V-targeting drug PKC412 produced synergistic growth-inhibitory effects in MCPV-1.1 cells. Together, CD30 is a promising new drug target for patients with CD30(+) advanced SM.

  17. Identification of Cytoplasmic Capping Targets Reveals a Role for Cap Homeostasis in Translation and mRNA Stability

    Directory of Open Access Journals (Sweden)

    Chandrama Mukherjee

    2012-09-01

    Full Text Available The notion that decapping leads irreversibly to messenger RNA (mRNA decay was contradicted by the identification of capped transcripts missing portions of their 5′ ends and a cytoplasmic complex that can restore the cap on uncapped mRNAs. In this study, we used accumulation of uncapped transcripts in cells inhibited for cytoplasmic capping to identify the targets of this pathway. Inhibition of cytoplasmic capping results in the destabilization of some transcripts and the redistribution of others from polysomes to nontranslating messenger ribonucleoproteins, where they accumulate in an uncapped state. Only a portion of the mRNA transcriptome is affected by cytoplasmic capping, and its targets encode proteins involved in nucleotide binding, RNA and protein localization, and the mitotic cell cycle. The 3′ untranslated regions of recapping targets are enriched for AU-rich elements and microRNA binding sites, both of which function in cap-dependent mRNA silencing. These findings identify a cyclical process of decapping and recapping that we term cap homeostasis.

  18. Close-up of primary and secondary asteroseismic CoRoT targets and the ground-based follow-up observations

    CERN Document Server

    Uytterhoeven, K; Rainer, M; Mantegazza, L; Zima, W; Aerts, C; Morel, T; Miglio, A; Lefever, K; Amado, P J; Mathias, P; Valtier, J C; Paparo, M; Benko, J M; CoRoT/SWG, the

    2007-01-01

    To optimise the science results of the asteroseismic part of the CoRoT satellite mission a complementary simultaneous ground-based observational campaign is organised for selected CoRoT targets. The observations include both high-resolution spectroscopic and multi-colour photometric data. We present the preliminary results of the analysis of the ground-based observations of three targets. A line-profile analysis of 216 high-resolution FEROS spectra of the delta Sct star HD 50844 reveals more than ten pulsation frequencies in the frequency range 5-18 c/d, including possibly one radial fundamental mode (6.92 c/d). Based on more than 600 multi-colour photometric datapoints of the beta Cep star HD180642, spanning about three years and obtained with different telescopes and different instruments, we confirm the presence of a dominant radial mode nu1=5.48695 c/d, and detect also its first two harmonics. We find evidence for a second mode nu2=0.3017 c/d, possibly a g-mode, and indications for two more frequencies in...

  19. Identification of Czech Metropolitan Regions: How to improve targeting of innovation policy

    Directory of Open Access Journals (Sweden)

    Klímová Viktorie

    2016-03-01

    Full Text Available Concepts of national and regional innovation systems can serve as an analytical framework forming the empirical base for innovation policy creation. It is possible to distinguish various types of these systems. One of these typologies is based on the assessment of innovation deficiencies. There are three types of regions: metropolitan, peripheral, and old industrial. Metropolitan regions can be characterized by a high level of research, innovation, and patent activity. The aims of this paper are to find relevant indicators that can be used as the basis for defining metropolitan regional innovation systems and using them for the identification of Czech metropolitan regions. The results of the point method combined with the cluster analysis showed that the capital city, Prague, as well as the South Moravian, Pardubice, Central Bohemian, Pilsen, and Liberec Regions can be defined as metropolitan regions.

  20. Investigation of antibacterial mechanism and identification of bacterial protein targets mediated by antibacterial medicinal plant extracts.

    Science.gov (United States)

    Yong, Ann-Li; Ooh, Keng-Fei; Ong, Hean-Chooi; Chai, Tsun-Thai; Wong, Fai-Chu

    2015-11-01

    In this paper, we investigated the antibacterial mechanism and potential therapeutic targets of three antibacterial medicinal plants. Upon treatment with the plant extracts, bacterial proteins were extracted and resolved using denaturing gel electrophoresis. Differentially-expressed bacterial proteins were excised from the gels and subjected to sequence analysis by MALDI TOF-TOF mass spectrometry. From our study, seven differentially expressed bacterial proteins (triacylglycerol lipase, N-acetylmuramoyl-L-alanine amidase, flagellin, outer membrane protein A, stringent starvation protein A, 30S ribosomal protein s1 and 60 kDa chaperonin) were identified. Additionally, scanning electron microscope study indicated morphological damages induced on bacterial cell surfaces. To the best of our knowledge, this represents the first time these bacterial proteins are being reported, following treatments with the antibacterial plant extracts. Further studies in this direction could lead to the detailed understanding of their inhibition mechanism and discovery of target-specific antibacterial agents. Copyright © 2014 Elsevier Ltd. All rights reserved.

  1. Identification and in vitro characterization of phage-displayed VHHs targeting VEGF

    DEFF Research Database (Denmark)

    Farajpour, Zahra; Rahbarizadeh, Fatemeh; Kazemi, Bahram;

    2014-01-01

    Vascular endothelial growth factor (VEGF) is a potential target for cancer treatment because of its role in angiogenesis and its overexpression in most human cancers. Currently, anti-VEGF antibodies have been shown to be promising tools for therapeutic applications. However, large size, poor tumor......-targeting purposes. The present study was undertaken to generate and characterize anti-VEGF VHHs from an immune VHH library using phage display. Four rounds of panning were performed, and selected VHHs were characterized using various immunological techniques. Assessment of the antigenic profile of VHHs was done......, significantly inhibited the endothelial cell growth in a dose-dependent manner. Taken together, our results indicate that ZFR-5 and other VHHs may be promising tools in cancer research and treatment....

  2. Identification of Ustilago maydis Aurora kinase as a novel antifungal target.

    Science.gov (United States)

    Tückmantel, Sandra; Greul, Jörg N; Janning, Petra; Brockmeyer, Andreas; Grütter, Christian; Simard, Jeffrey R; Gutbrod, Oliver; Beck, Michael E; Tietjen, Klaus; Rauh, Daniel; Schreier, Peter H

    2011-09-16

    Infestation of crops by pathogenic fungi has continued to have a major impact by reducing yield and quality, emphasizing the need to identify new targets and develop new agents to improve methods of crop protection. Here we present Aurora kinase from the phytopathogenic fungus Ustilago maydis as a novel target for N-substituted diaminopyrimidines, a class of small-molecule kinase inhibitors. We show that Aurora kinase is essential in U. maydis and that diaminopyrimidines inhibit its activity in vitro. Furthermore, we observed an overall good correlation between in vitro inhibition of Aurora kinase and growth inhibition of diverse fungi in vivo. In vitro inhibition assays with Ustilago and human Aurora kinases indicate that some compounds of the N-substituted diaminopyrimidine class show specificity for the Ustilago enzyme, thus revealing their potential as selective fungicides.

  3. Performance of targeted screening for the identification of hypertension in children.

    Science.gov (United States)

    Bloetzer, Clemens; Bovet, Pascal; Paccaud, Fred; Burnier, Michel; Chiolero, Arnaud

    2017-04-01

    Targeted screening of hypertension in childhood might be more efficient than universal screening. We estimated the sensitivity, specificity, negative and positive predictive values of combined parental history of hypertension and overweight/obesity for the diagnosis of hypertension in 5207 children aged 10-14 years. Children had hypertension if they had sustained elevated blood pressure over three separate visits. The prevalence of hypertension was 2.2%. 14% of children were overweight or obese, 20% had a positive history of hypertension in at least one parent and 30% had either or both conditions. Targeted screening of hypertension to children with either overweight/obesity or with hypertensive parents limits the proportion of children (30%) to screen and identifies up to 65% of all hypertensive cases.

  4. Comprehensive Identification of SUMO2/3 Targets and Their Dynamics during Mitosis

    DEFF Research Database (Denmark)

    Schou, Julie; Kelstrup, Christian D; Hayward, Daniel G

    2014-01-01

    During mitosis large alterations in cellular structures occur rapidly, which to a large extent is regulated by post-translational modification of proteins. Modification of proteins with the small ubiquitin-related protein SUMO2/3 regulates mitotic progression, but few mitotic targets have been...... identified so far. To deepen our understanding of SUMO2/3 during this window of the cell cycle, we undertook a comprehensive proteomic characterization of SUMO2/3 modified proteins in mitosis and upon mitotic exit. We developed an efficient tandem affinity purification strategy of SUMO2/3 modified proteins...... from mitotic cells. Combining this purification strategy with cell synchronization procedures and quantitative mass spectrometry allowed for the mapping of numerous novel targets and their dynamics as cells progressed out of mitosis. This identified RhoGDIα as a major SUMO2/3 modified protein...

  5. Functional Analysis of Barley Powdery Mildew Effector Candidates and Identification of their Barley Targets

    DEFF Research Database (Denmark)

    Ahmed, Ali Abdurehim

    about the function of many CSEPs in virulence and the identities of their host targets. In this PhD study, we investigated the function of nine CSEPs and found that CSEP0081, CSEP0105, CSEP0162 and CSEP0254 act as effectors by promoting the Bgh infection success. Independent silencing of these CSEPs...... to the cytosol and the nucleus of barley epidermal cells. Furthermore, CSEP0162 and CSEP0254 accumulated in the extrahaustorial matrix in Bgh-infected cells. This implies that their virulence targets may localize in the same cellular compartments. Using yeast two-hybrid screens, two barley small heat shock...... misfolding and aggregation. Through their chaperone activity, some sHsps contribute to pathogen defence by stabilizing intracellular proteins, including resistance and defence signalling proteins. In this study, we validated the chaperone activity of the barley Hsp16.9, which prevented the aggregation...

  6. Identification of pyruvate kinase in methicillin-resistant Staphylococcus aureus as a novel antimicrobial drug target.

    Science.gov (United States)

    Zoraghi, Roya; See, Raymond H; Axerio-Cilies, Peter; Kumar, Nag S; Gong, Huansheng; Moreau, Anne; Hsing, Michael; Kaur, Sukhbir; Swayze, Richard D; Worrall, Liam; Amandoron, Emily; Lian, Tian; Jackson, Linda; Jiang, Jihong; Thorson, Lisa; Labriere, Christophe; Foster, Leonard; Brunham, Robert C; McMaster, William R; Finlay, B Brett; Strynadka, Natalie C; Cherkasov, Artem; Young, Robert N; Reiner, Neil E

    2011-05-01

    Novel classes of antimicrobials are needed to address the challenge of multidrug-resistant bacteria such as methicillin-resistant Staphylococcus aureus (MRSA). Using the architecture of the MRSA interactome, we identified pyruvate kinase (PK) as a potential novel drug target based upon it being a highly connected, essential hub in the MRSA interactome. Structural modeling, including X-ray crystallography, revealed discrete features of PK in MRSA, which appeared suitable for the selective targeting of the bacterial enzyme. In silico library screening combined with functional enzymatic assays identified an acyl hydrazone-based compound (IS-130) as a potent MRSA PK inhibitor (50% inhibitory concentration [IC50] of 0.1 μM) with >1,000-fold selectivity over human PK isoforms. Medicinal chemistry around the IS-130 scaffold identified analogs that more potently and selectively inhibited MRSA PK enzymatic activity and S. aureus growth in vitro (MIC of 1 to 5 μg/ml). These novel anti-PK compounds were found to possess antistaphylococcal activity, including both MRSA and multidrug-resistant S. aureus (MDRSA) strains. These compounds also exhibited exceptional antibacterial activities against other Gram-positive genera, including enterococci and streptococci. PK lead compounds were found to be noncompetitive inhibitors and were bactericidal. In addition, mutants with significant increases in MICs were not isolated after 25 bacterial passages in culture, indicating that resistance may be slow to emerge. These findings validate the principles of network science as a powerful approach to identify novel antibacterial drug targets. They also provide a proof of principle, based upon PK in MRSA, for a research platform aimed at discovering and optimizing selective inhibitors of novel bacterial targets where human orthologs exist, as leads for anti-infective drug development.

  7. Identification of Soldier Behaviors Associated with Search and Target Acquisition (STA)

    Science.gov (United States)

    2010-05-01

    3 UNCLASSIFIED different gaps. Each of these FACTs focused on several critical research areas ( CRAs ). The Fiscal Year (FY) 08 Soldier FACT Call...for Proposals identified the following CRA : Soldier Search and Target Acquisition (STA): Determine validity of current Soldier STA processes for...place him in a position where he can engage any threats (i.e., can see where to aim and shoot ). The order of behaviors for “audio cues” and

  8. Identification of novel RHPS4-derivative ligands with improved toxicological profiles and telomere-targeting activities.

    Science.gov (United States)

    Rizzo, Angela; Iachettini, Sara; Zizza, Pasquale; Cingolani, Chiara; Porru, Manuela; Artuso, Simona; Stevens, Malcolm; Hummersone, Marc; Biroccio, Annamaria; Salvati, Erica; Leonetti, Carlo

    2014-10-06

    The pentacyclic acridinium salt RHPS4 (3,11-difluoro-6,8,13-trimethyl-8H-quino [4,3,2-kl] acridinium methosulfate, compound 1) is one of the most interesting DNA G-quadruplex binding molecules due to its high efficacy in tumor cell growth inhibition both in in vitro models and in vivo against human tumor xenografts in combination with conventional chemotherapeutics. Despite compound 1 having desirable chemical and pharmaceutical properties, its potential as a therapeutic agent is compromised by off-target effects on cardiovascular physiology. In this paper we report a new series of structurally-related compounds which were developed in an attempt to minimize its off-target profile, but maintaining the same favorable chemical and pharmacological features of the lead compound. By performing a comparative analysis it was possible to identify which derivatives had the following properties: (i) to show a reduced capacity in respect to compound 1 to inhibit the hERG tail current tested in a patch clamp assay and/or to interact with the human recombinant β2 receptor; (ii) to maintain both a good G4-binding affinity and cancer cell selectivity; and (iii) to trigger DNA damage with specific telomere uncapping. These studies allowed us to identify a novel G4-stabilizing molecule, compound 8, being characterized by reduced off-target effects and potent telomere on-target properties compared to the prototypic compound 1. Moreover, compound 8 shares with compound 1 the same molecular mode of action and an anti-tumour activity specifically restricted to replicating cells, as evident with its particularly efficient activity in combination therapy with a topoisomerase I inhibitor. In conclusion, we have identified a new pentacyclic derivative 8 having suitable properties to be the focus of further investigations as a clinical candidate for cancer therapy.

  9. Dana-Farber Cancer Institute: Identification of Therapeutic Targets Across Cancer Types | Office of Cancer Genomics

    Science.gov (United States)

    The Dana Farber Cancer Institute CTD2 Center focuses on the use of high-throughput genetic and bioinformatic approaches to identify and credential oncogenes and co-dependencies in cancers. This Center aims to provide the cancer research community with information that will facilitate the prioritization of targets based on both genomic and functional evidence, inform the most appropriate genetic context for downstream mechanistic and validation studies, and enable the translation of this information into therapeutics and diagnostics.

  10. Crowd sourcing a new paradigm for interactome driven drug target identification in Mycobacterium tuberculosis.

    Science.gov (United States)

    Vashisht, Rohit; Mondal, Anupam Kumar; Jain, Akanksha; Shah, Anup; Vishnoi, Priti; Priyadarshini, Priyanka; Bhattacharyya, Kausik; Rohira, Harsha; Bhat, Ashwini G; Passi, Anurag; Mukherjee, Keya; Choudhary, Kumari Sonal; Kumar, Vikas; Arora, Anshula; Munusamy, Prabhakaran; Subramanian, Ahalyaa; Venkatachalam, Aparna; Gayathri, S; Raj, Sweety; Chitra, Vijaya; Verma, Kaveri; Zaheer, Salman; Balaganesh, J; Gurusamy, Malarvizhi; Razeeth, Mohammed; Raja, Ilamathi; Thandapani, Madhumohan; Mevada, Vishal; Soni, Raviraj; Rana, Shruti; Ramanna, Girish Muthagadhalli; Raghavan, Swetha; Subramanya, Sunil N; Kholia, Trupti; Patel, Rajesh; Bhavnani, Varsha; Chiranjeevi, Lakavath; Sengupta, Soumi; Singh, Pankaj Kumar; Atray, Naresh; Gandhi, Swati; Avasthi, Tiruvayipati Suma; Nisthar, Shefin; Anurag, Meenakshi; Sharma, Pratibha; Hasija, Yasha; Dash, Debasis; Sharma, Arun; Scaria, Vinod; Thomas, Zakir; Chandra, Nagasuma; Brahmachari, Samir K; Bhardwaj, Anshu

    2012-01-01

    A decade since the availability of Mycobacterium tuberculosis (Mtb) genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative 'Connect to Decode' (C2D) to generate the first and largest manually curated interactome of Mtb termed 'interactome pathway' (IPW), encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.

  11. Identification of Vimentin as a Potential Therapeutic Target against HIV Infection.

    Science.gov (United States)

    Fernández-Ortega, Celia; Ramírez, Anna; Casillas, Dionne; Paneque, Taimi; Ubieta, Raimundo; Dubed, Marta; Navea, Leonor; Castellanos-Serra, Lila; Duarte, Carlos; Falcon, Viviana; Reyes, Osvaldo; Garay, Hilda; Silva, Eladio; Noa, Enrique; Ramos, Yassel; Besada, Vladimir; Betancourt, Lázaro

    2016-06-15

    A combination of antiviral drugs known as antiretroviral therapy (ART) has shown effectiveness against the human immunodeficiency virus (HIV). ART has markedly decreased mortality and morbidity among HIV-infected patients, having even reduced HIV transmission. However, an important current disadvantage, resistance development, remains to be solved. Hope is focused on developing drugs against cellular targets. This strategy is expected to prevent the emergence of viral resistance. In this study, using a comparative proteomic approach in MT4 cells treated with an anti-HIV leukocyte extract, we identified vimentin, a molecule forming intermediate filaments in the cell, as a possible target against HIV infection. We demonstrated a strong reduction of an HIV-1 based lentivirus expressing the enhanced green fluorescent protein (eGFP) in vimentin knockdown cells, and a noteworthy decrease of HIV-1 capsid protein antigen (CAp24) in those cells using a multiround infectivity assay. Electron micrographs showed changes in the structure of intermediate filaments when MT4 cells were treated with an anti-HIV leukocyte extract. Changes in the structure of intermediate filaments were also observed in vimentin knockdown MT4 cells. A synthetic peptide derived from a cytoskeleton protein showed potent inhibitory activity on HIV-1 infection, and low cytotoxicity. Our data suggest that vimentin can be a suitable target to inhibit HIV-1.

  12. Target-based identification of whole-cell active inhibitors of biotin biosynthesis in Mycobacterium tuberculosis.

    Science.gov (United States)

    Park, Sae Woong; Casalena, Dominick E; Wilson, Daniel J; Dai, Ran; Nag, Partha P; Liu, Feng; Boyce, Jim P; Bittker, Joshua A; Schreiber, Stuart L; Finzel, Barry C; Schnappinger, Dirk; Aldrich, Courtney C

    2015-01-22

    Biotin biosynthesis is essential for survival and persistence of Mycobacterium tuberculosis (Mtb) in vivo. The aminotransferase BioA, which catalyzes the antepenultimate step in the biotin pathway, has been established as a promising target due to its vulnerability to chemical inhibition. We performed high-throughput screening (HTS) employing a fluorescence displacement assay and identified a diverse set of potent inhibitors including many diversity-oriented synthesis (DOS) scaffolds. To efficiently select only hits targeting biotin biosynthesis, we then deployed a whole-cell counterscreen in biotin-free and biotin-containing medium against wild-type Mtb and in parallel with isogenic bioA Mtb strains that possess differential levels of BioA expression. This counterscreen proved crucial to filter out compounds whose whole-cell activity was off target as well as identify hits with weak, but measurable whole-cell activity in BioA-depleted strains. Several of the most promising hits were cocrystallized with BioA to provide a framework for future structure-based drug design efforts.

  13. Identification of a VxP targeting signal in the flagellar Na+/K+-ATPase

    Science.gov (United States)

    Laird, Joseph G.; Pan, Yuan; Modestou, Modestos; Yamaguchi, David M.; Song, Hongman; Sokolov, Maxim; Baker, Sheila A.

    2015-01-01

    Na+/K+-ATPase (NKA) participates in setting electrochemical gradients, cardiotonic steroid signaling, and cellular adhesion. Distinct isoforms of NKA are found in different tissues and subcellular localization patterns. For example, NKA α1 is widely expressed, NKA α3 is enriched in neurons, and NKA α4 is a testes specific isoform found in sperm flagella. In some tissues, ankyrin, a key component of the membrane cytoskeleton, can regulate the trafficking of NKA. In the retina, NKA and ankyrin-B are expressed in multiple cell types and immunostaining for each is striking in the synaptic layers. Labeling for NKA is also prominent along the inner segment plasma membrane of photoreceptors. NKA co-immunoprecipitates with ankyrin-B, but on a subcellular level co-localization of these two proteins varies dependent on the cell type. We used transgenic X. laevis tadpoles to evaluate the subcellular trafficking of NKA in photoreceptors. GFP-NKA α3 and α1 localized to the inner segment plasma membrane, but α4 localized to outer segments. We identified a VxP motif responsible for the outer segment targeting by using a series of chimeric and mutant NKA constructs. This motif is similar to previously identified ciliary targeting motifs. Given the structural similarities between outer segments and flagella, our findings shed light on the subcellular targeting of this testes specific NKA isoform. PMID:26373354

  14. Identification of cellular deoxyhypusine synthase as a novel target for antiretroviral therapy

    Science.gov (United States)

    Hauber, Ilona; Bevec, Dorian; Heukeshoven, Jochen; Krätzer, Friedrich; Horn, Florian; Choidas, Axel; Harrer, Thomas; Hauber, Joachim

    2005-01-01

    The introduction of highly active antiretroviral therapy (HAART) has significantly decreased morbidity and mortality among patients infected with HIV-1. However, HIV-1 can acquire resistance against all currently available antiretroviral drugs targeting viral reverse transcriptase, protease, and gp41. Moreover, in a growing number of patients, the development of multidrug-resistant viruses compromises HAART efficacy and limits therapeutic options. Therefore, it is an ongoing task to develop new drugs and to identify new targets for antiretroviral therapy. Here, we identified the guanylhydrazone CNI-1493 as an efficient inhibitor of human deoxyhypusine synthase (DHS). By inhibiting DHS, this compound suppresses hypusine formation and, thereby, activation of eukaryotic initiation factor 5A (eIF-5A), a cellular cofactor of the HIV-1 Rev regulatory protein. We demonstrate that inhibition of DHS by CNI-1493 or RNA interference efficiently suppressed the retroviral replication cycle in cell culture and primary cells. We show that CNI-1493 inhibits replication of macrophage- and T cell–tropic laboratory strains, clinical isolates, and viral strains with high-level resistance to inhibitors of viral protease and reverse transcriptase. Moreover, no measurable drug-induced adverse effects on cell cycle transition, apoptosis, and general cytotoxicity were observed. Therefore, human DHS represents a novel and promising drug target for the development of advanced antiretroviral therapies, particularly for the inhibition of multidrug-resistant viruses. PMID:15630446

  15. Identification of a Drug Targeting an Intrinsically Disordered Protein Involved in Pancreatic Adenocarcinoma

    Science.gov (United States)

    Neira, José L.; Bintz, Jennifer; Arruebo, María; Rizzuti, Bruno; Bonacci, Thomas; Vega, Sonia; Lanas, Angel; Velázquez-Campoy, Adrián; Iovanna, Juan L.; Abián, Olga

    2017-01-01

    Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor development in vivo on xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the ‘fuzzy’ interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs.

  16. Identification of gene targets eliciting improved alcohol tolerance in Saccharomyces cerevisiae through inverse metabolic engineering.

    Science.gov (United States)

    Hong, Min-Eui; Lee, Ki-Sung; Yu, Byung Jo; Sung, Young-Je; Park, Sung Min; Koo, Hyun Min; Kweon, Dae-Hyuk; Park, Jae Chan; Jin, Yong-Su

    2010-08-20

    The economic production of biofuels from renewable biomass using Saccharomyces cerevisiae requires tolerance to high concentrations of sugar and alcohol. Here we applied an inverse metabolic engineering approach to identify endogenous gene targets conferring improved alcohol tolerance in S. cerevisiae. After transformation with a S. cerevisiae genomic library, enrichment of the transformants exhibiting improved tolerance was performed by serial subculture in the presence of iso-butanol (1%). Through sequence analysis of the isolated plasmids from the selected transformants, four endogenous S. cerevisiae genes were identified as overexpression targets eliciting improved tolerance to both iso-butanol and ethanol. Overexpression of INO1, DOG1, HAL1 or a truncated form of MSN2 resulted in remarkably increased tolerance to high concentrations of iso-butanol and ethanol. Overexpression of INO1 elicited the highest ethanol tolerance, resulting in higher titers and volumetric productivities in the fermentation experiments performed with high glucose concentrations. In addition, the INO1-overexpressing strain showed a threefold increase in the specific growth rate as compared to that of the control strain under conditions of high levels of glucose (10%) and ethanol (5%). Although alcohol tolerance in yeast is a complex trait affected by simultaneous interactions of many genes, our results using a genomic library reveal potential target genes for better understanding and possible engineering of metabolic pathways underlying alcohol tolerance phenotypes. Crown Copyright 2010. Published by Elsevier B.V. All rights reserved.

  17. Crowd sourcing a new paradigm for interactome driven drug target identification in Mycobacterium tuberculosis.

    Directory of Open Access Journals (Sweden)

    Rohit Vashisht

    Full Text Available A decade since the availability of Mycobacterium tuberculosis (Mtb genome sequence, no promising drug has seen the light of the day. This not only indicates the challenges in discovering new drugs but also suggests a gap in our current understanding of Mtb biology. We attempt to bridge this gap by carrying out extensive re-annotation and constructing a systems level protein interaction map of Mtb with an objective of finding novel drug target candidates. Towards this, we synergized crowd sourcing and social networking methods through an initiative 'Connect to Decode' (C2D to generate the first and largest manually curated interactome of Mtb termed 'interactome pathway' (IPW, encompassing a total of 1434 proteins connected through 2575 functional relationships. Interactions leading to gene regulation, signal transduction, metabolism, structural complex formation have been catalogued. In the process, we have functionally annotated 87% of the Mtb genome in context of gene products. We further combine IPW with STRING based network to report central proteins, which may be assessed as potential drug targets for development of drugs with least possible side effects. The fact that five of the 17 predicted drug targets are already experimentally validated either genetically or biochemically lends credence to our unique approach.

  18. [Construction and identification of small interfering RNA expression vector targeting ATF-2 gene].

    Science.gov (United States)

    Mao, Wei-wei; Xiong, Peng; Han, Feng; Hu, Zhi-jian

    2012-09-01

    To construct an eukaryotic expression vector for RNA interference targeting activating transcription factor 2 (ATF-2) gene, and explore its effect on proliferation and apoptosis of HepG2 cells. Two complementary oligonucleotides were synthesized based on ATF-2 mRNA sequence. The annealed fragment was inserted into the vector PBA-siU6. The recombinant plasmid PBA-siATF-2 was confirmed by DNA sequencing and transfected into HepG2 cells mediated by liposome. After transfection, ATF-2 protein was detected by Western blotting. The cellular growth activity and apoptosis rate were measured by MTT assay and flow cytometry, respectively. Recombinant plasmid expressing siRNA targeting ATF-2 gene was confirmed by DNA sequencing. Plasmid transfection down-regulated the level of ATF-2 protein in HepG2 cells, which blocked cellular growth and induced cell apoptosis. The eukaryotic expression vector for RNA interference targeting ATF-2 gene was constructed successfully, which inhibits HepG2 cell proliferation and induces cell apoptosis.

  19. Elucidation of the Cellular Interactome of Ebola Virus Nucleoprotein and Identification of Therapeutic Targets.

    Science.gov (United States)

    García-Dorival, Isabel; Wu, Weining; Armstrong, Stuart D; Barr, John N; Carroll, Miles W; Hewson, Roger; Hiscox, Julian A

    2016-12-02

    Ebola virus (EBOV) infection results in severe disease and in some cases lethal hemorrhagic fever. The infection is directed by seven viral genes that encode nine viral proteins. By definition, viruses are obligate intracellular parasites and require aspects of host cell biology in order to replicate their genetic material, assemble new virus particles, and subvert host cell antiviral responses. Currently licensed antivirals are targeted against viral proteins to inhibit their function. However, experience with treating HIV and influenza virus demonstrates that resistant viruses are soon selected. An emerging area in virology is to transiently target host cell proteins that play critical proviral roles in virus biology, especially for acute infections. This has the advantage that the protein being targeted is evolutionary removed from the genome of the virus. Proteomics can aid in discovery biology and identify cellular proteins that may be utilized by the virus to facilitate infection. This work focused on defining the interactome of the EBOV nucleoprotein and identified that cellular chaperones, including HSP70, associate with this protein to promote stability. Utilization of a mini-genome replication system based on a recent Makona isolate demonstrated that disrupting the stability of NP had an adverse effect on viral RNA synthesis.

  20. Identification of elongation factor G as the conserved cellular target of argyrin B.

    Science.gov (United States)

    Nyfeler, Beat; Hoepfner, Dominic; Palestrant, Deborah; Kirby, Christina A; Whitehead, Lewis; Yu, Robert; Deng, Gejing; Caughlan, Ruth E; Woods, Angela L; Jones, Adriana K; Barnes, S Whitney; Walker, John R; Gaulis, Swann; Hauy, Ervan; Brachmann, Saskia M; Krastel, Philipp; Studer, Christian; Riedl, Ralph; Estoppey, David; Aust, Thomas; Movva, N Rao; Wang, Zuncai; Salcius, Michael; Michaud, Gregory A; McAllister, Gregory; Murphy, Leon O; Tallarico, John A; Wilson, Christopher J; Dean, Charles R

    2012-01-01

    Argyrins, produced by myxobacteria and actinomycetes, are cyclic octapeptides with antibacterial and antitumor activity. Here, we identify elongation factor G (EF-G) as the cellular target of argyrin B in bacteria, via resistant mutant selection and whole genome sequencing, biophysical binding studies and crystallography. Argyrin B binds a novel allosteric pocket in EF-G, distinct from the known EF-G inhibitor antibiotic fusidic acid, revealing a new mode of protein synthesis inhibition. In eukaryotic cells, argyrin B was found to target mitochondrial elongation factor G1 (EF-G1), the closest homologue of bacterial EF-G. By blocking mitochondrial translation, argyrin B depletes electron transport components and inhibits the growth of yeast and tumor cells. Further supporting direct inhibition of EF-G1, expression of an argyrin B-binding deficient EF-G1 L693Q variant partially rescued argyrin B-sensitivity in tumor cells. In summary, we show that argyrin B is an antibacterial and cytotoxic agent that inhibits the evolutionarily conserved target EF-G, blocking protein synthesis in bacteria and mitochondrial translation in yeast and mammalian cells.

  1. Identification of elongation factor G as the conserved cellular target of argyrin B.

    Directory of Open Access Journals (Sweden)

    Beat Nyfeler

    Full Text Available Argyrins, produced by myxobacteria and actinomycetes, are cyclic octapeptides with antibacterial and antitumor activity. Here, we identify elongation factor G (EF-G as the cellular target of argyrin B in bacteria, via resistant mutant selection and whole genome sequencing, biophysical binding studies and crystallography. Argyrin B binds a novel allosteric pocket in EF-G, distinct from the known EF-G inhibitor antibiotic fusidic acid, revealing a new mode of protein synthesis inhibition. In eukaryotic cells, argyrin B was found to target mitochondrial elongation factor G1 (EF-G1, the closest homologue of bacterial EF-G. By blocking mitochondrial translation, argyrin B depletes electron transport components and inhibits the growth of yeast and tumor cells. Further supporting direct inhibition of EF-G1, expression of an argyrin B-binding deficient EF-G1 L693Q variant partially rescued argyrin B-sensitivity in tumor cells. In summary, we show that argyrin B is an antibacterial and cytotoxic agent that inhibits the evolutionarily conserved target EF-G, blocking protein synthesis in bacteria and mitochondrial translation in yeast and mammalian cells.

  2. Target identification of volatile metabolites to allow the differentiation of lactic acid bacteria by gas chromatography-ion mobility spectrometry.

    Science.gov (United States)

    Gallegos, Janneth; Arce, Cristina; Jordano, Rafael; Arce, Lourdes; Medina, Luis M

    2017-04-01

    The purpose of this work was to study the potential of gas chromatography-ion mobility spectrometry (GC-IMS) to differentiate lactic acid bacteria (LAB) through target identification and fingerprints of volatile metabolites. The LAB selected were used as reference strains for their influence in the flavour of cheese. The four strains of LAB can be distinguished by the fingerprints generated by the volatile organic compounds (VOCs) emitted. 2-butanone, 2-pentanone, 2-heptanone and 3-methyl-1-butanol were identified as relevant VOCs for Lactobacillus casei and Lactobacillus paracasei subsp. paracasei. 2-Butanone and 3-methyl-1-butanol were identified in Lactococcus lactis subsp. lactis and Lactococcus cremoris subsp. cremoris. The IMS signals monitoring during a 24-30h period showed the growth of the LAB in vitro. The results demonstrated that GC-IMS is a useful technology for bacteria recognition and also for screening the aromatic potential of new isolates of LAB.

  3. Identification of magnetic anomalies based on ground magnetic data analysis using multifractal modelling: a case study in Qoja-Kandi, East Azerbaijan Province, Iran

    Science.gov (United States)

    Mansouri, E.; Feizi, F.; Karbalaei Ramezanali, A. A.

    2015-10-01

    Ground magnetic anomaly separation using the reduction-to-the-pole (RTP) technique and the fractal concentration-area (C-A) method has been applied to the Qoja-Kandi prospecting area in northwestern Iran. The geophysical survey resulting in the ground magnetic data was conducted for magnetic element exploration. Firstly, the RTP technique was applied to recognize underground magnetic anomalies. RTP anomalies were classified into different populations based on the current method. For this reason, drilling point area determination by the RTP technique was complicated for magnetic anomalies, which are in the center and north of the studied area. Next, the C-A method was applied to the RTP magnetic anomalies (RTP-MA) to demonstrate magnetic susceptibility concentrations. This identification was appropriate for increasing the resolution of the drilling point area determination and decreasing the drilling risk issue, due to the economic costs of underground prospecting. In this study, the results of C-A modelling on the RTP-MA are compared with 8 borehole data. The results show that there is a good correlation between anomalies derived via the C-A method and the log report of boreholes. Two boreholes were drilled in magnetic susceptibility concentrations, based on multifractal modelling data analyses, between 63 533.1 and 66 296 nT. Drilling results showed appropriate magnetite thickness with grades greater than 20 % Fe. The total associated with anomalies containing andesite units hosts iron mineralization.

  4. Identification of magnetic anomalies based on ground magnetic data analysis using multifractal modeling: a case study in Qoja-Kandi, East Azerbaijan Province, Iran

    Science.gov (United States)

    Mansouri, E.; Feizi, F.; Karbalaei Ramezanali, A. A.

    2015-07-01

    Ground magnetic anomaly separation using reduction-to-the-pole (RTP) technique and the fractal concentration-area (C-A) method has been applied to the Qoja-Kandi prosepecting area in NW Iran. The geophysical survey that resulted in the ground magnetic data was conducted for magnetic elements exploration. Firstly, RTP technique was applied for recognizing underground magnetic anomalies. RTP anomalies was classified to different populations based on this method. For this reason, drilling points determination with RTP technique was complicated. Next, C-A method was applied on the RTP-Magnetic-Anomalies (RTP-MA) for demonstrating magnetic susceptibility concentration. This identification was appropriate for increasing the resolution of the drilling points determination and decreasing the drilling risk, due to the economic costs of underground prospecting. In this study, the results of C-A Modeling on the RTP-MA are compared with 8 borehole data. The results show there is good correlation between anomalies derived via C-A method and log report of boreholes. Two boreholes were drilled in magnetic susceptibility concentration, based on multifractal modeling data analyses, between 63 533.1 and 66 296 nT. Drilling results show appropriate magnetite thickness with the grades greater than 20 % Fe total. Also, anomalies associated with andesite units host iron mineralization.

  5. REAL TIME PCR IDENTIFICATION FOR TARGET ADJUNCTIVE ANTIBIOTIC THERAPY OF SEVERE CHRONIC PERIODONTITIS. PART II - MICROBIOLOGICAL EFFECTIVENESS.

    Directory of Open Access Journals (Sweden)

    Kamen Kotsilkov

    2014-10-01

    Full Text Available INTRODUCTION: Antibiotic use in chronic periodontitis may result in improvement in periodontal status, although many questions regarding the indications for this therapy remain unanswered. The polymicrobial etiology of the periodontal infection hinders the choice of the proper antibiotic agent. Furthermore the indiscriminate use of antibiotics could lead to high levels of resistance and to various adverse reactions. In the recent years a various molecular diagnostics protocols were proposed in order to facilitate the decision for adjunctive antibiotic administration. OBJECTIVE: The aim of this study is to compare the microbiological effectiveness of adjunctive antibiotic administration with the mechanical periodontal therapy. METHODS: 30 patients with severe chronic periodontitis were enrolled in this study and were divided in 3 groups: Control group – with mechanical debridement only. Test group 1 – with combined adjunctive antibiotic administration using Amoxicillin+ Metronidazole. Test group 2 – with target antibiotic administration according to the resuts from the Real Time PCR identification. RESULTS: The prevalence of all the isolated microorganisms (exept. E.nodatum and C.gingivalis in Test Group 2 demonstrates statistically significant reduction compared with the other treatment approaches. Almost complete elimination was registered for the consensus pathogens from the red and orange complexes (above 99% and 100% for P.intemedia. CONCLUSION: The adjunct antibiotic treatment targeted with Real-Time PCR identification demonstrates almost complete elimination of the putative periodontal pathogens in the deep periodontal pockets in patients with severe chronic periodontitis. This result suggests slower recolonisation of these habitats thus limiting the risk for progression of the periodontal destruction.

  6. High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

    Energy Technology Data Exchange (ETDEWEB)

    Pan, Jian-Bo [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Nan; Pan, Wen; Hong, Ru [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Wang, Hao [Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China); Ji, Zhi-Liang, E-mail: appo@xmu.edu.cn [State Key Laboratory of Stress Cell Biology, School of Life Sciences, Xiamen University, Xiamen, Fujian 361102 (China); Department of Chemical Biology, College of Chemistry and Chemical Engineering, The Key Laboratory for Chemical Biology of Fujian Province, Xiamen University, Xiamen, Fujian 361005 (China)

    2014-01-01

    Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPs that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.

  7. Identification of Thiotetronic Acid Antibiotic Biosynthetic Pathways by Target-directed Genome Mining.

    Science.gov (United States)

    Tang, Xiaoyu; Li, Jie; Millán-Aguiñaga, Natalie; Zhang, Jia Jia; O'Neill, Ellis C; Ugalde, Juan A; Jensen, Paul R; Mantovani, Simone M; Moore, Bradley S

    2015-12-18

    Recent genome sequencing efforts have led to the rapid accumulation of uncharacterized or "orphaned" secondary metabolic biosynthesis gene clusters (BGCs) in public databases. This increase in DNA-sequenced big data has given rise to significant challenges in the applied field of natural product genome mining, including (i) how to prioritize the characterization of orphan BGCs and (ii) how to rapidly connect genes to biosynthesized small molecules. Here, we show that by correlating putative antibiotic resistance genes that encode target-modified proteins with orphan BGCs, we predict the biological function of pathway specific small molecules before they have been revealed in a process we call target-directed genome mining. By querying the pan-genome of 86 Salinispora bacterial genomes for duplicated house-keeping genes colocalized with natural product BGCs, we prioritized an orphan polyketide synthase-nonribosomal peptide synthetase hybrid BGC (tlm) with a putative fatty acid synthase resistance gene. We employed a new synthetic double-stranded DNA-mediated cloning strategy based on transformation-associated recombination to efficiently capture tlm and the related ttm BGCs directly from genomic DNA and to heterologously express them in Streptomyces hosts. We show the production of a group of unusual thiotetronic acid natural products, including the well-known fatty acid synthase inhibitor thiolactomycin that was first described over 30 years ago, yet never at the genetic level in regards to biosynthesis and autoresistance. This finding not only validates the target-directed genome mining strategy for the discovery of antibiotic producing gene clusters without a priori knowledge of the molecule synthesized but also paves the way for the investigation of novel enzymology involved in thiotetronic acid natural product biosynthesis.

  8. An Approach for Identification of Novel Drug Targets in Streptococcus pyogenes SF370 Through Pathway Analysis.

    Science.gov (United States)

    Singh, Satendra; Singh, Dev Bukhsh; Singh, Anamika; Gautam, Budhayash; Ram, Gurudayal; Dwivedi, Seema; Ramteke, Pramod W

    2016-12-01

    Streptococcus pyogenes is one of the most important pathogens as it is involved in various infections affecting upper respiratory tract and skin. Due to the emergence of multidrug resistance and cross-resistance, S. Pyogenes is becoming more pathogenic and dangerous. In the present study, an in silico comparative analysis of total 65 metabolic pathways of the host (Homo sapiens) and the pathogen was performed. Initially, 486 paralogous enzymes were identified so that they can be removed from possible drug target list. The 105 enzymes of the biochemical pathways of S. pyogenes from the KEGG metabolic pathway database were compared with the proteins from the Homo sapiens by performing a BLASTP search against the non-redundant database restricted to the Homo sapiens subset. Out of these, 83 enzymes were identified as non-human homologous while 30 enzymes of inadequate amino acid length were removed for further processing. Essential enzymes were finally mined from remaining 53 enzymes. Finally, 28 essential enzymes were identified in S. pyogenes SF370 (serotype M1). In subcellular localization study, 18 enzymes were predicted with cytoplasmic localization and ten enzymes with the membrane localization. These ten enzymes with putative membrane localization should be of particular interest. Acyl-carrier-protein S-malonyltransferase, DNA polymerase III subunit beta and dihydropteroate synthase are novel drug targets and thus can be used to design potential inhibitors against S. pyogenes infection. 3D structure of dihydropteroate synthase was modeled and validated that can be used for virtual screening and interaction study of potential inhibitors with the target enzyme.

  9. Phenotypic alteration and target gene identification using combinatorial libraries of zinc finger proteins in prokaryotic cells.

    Science.gov (United States)

    Park, Kyung-Soon; Jang, Young-Soon; Lee, Horim; Kim, Jin-Soo

    2005-08-01

    We have developed a method with prokaryotic organisms that uses randomized libraries of zinc finger-containing artificial transcription factors to induce phenotypic variations and to identify genes involved in the generation of a specific phenotype of interest. Combining chromatin immunoprecipitation experiments and in silico prediction of target DNA binding sequences for the artificial transcription factors, we identified ubiX, whose down-regulation correlates with the thermotolerance phenotype in Escherichia coli. Our results show that randomized libraries of artificial transcription factors are powerful tools for functional genomic studies.

  10. Methodologies and Application of New Target Identification, Drug Action Mechanism Investigation and New Molecular Entity Discovery

    Institute of Scientific and Technical Information of China (English)

    2011-01-01

    @@ The group, headed by Prof.JIANG Hualiang with the CAS Shanghai Institute of Materia Medica, has been centering on the basic research of pharmaceutical science, including identifying new targets, studying new drug action mechanisms and discovering new drug candidates.On the basis of new methodology development, an effective multi-disciplinary research platform for drug research and discovery has been established through the integration of different disciplines of computational chemistry, organic synthesis, molecular and cellular biology.A bunch of creative results have been achieved in these areas.

  11. Supplemental Student Support: Detection and Identification of Buried Targets using Time Reversal Acoustics

    Science.gov (United States)

    2009-11-04

    Stainless steel spherical shell target used in experiments. Weights are clamped to eyehooks located at the poles of the sphere...The test tank is made of galvanized steel and has internal dimensions 0.75 m wide x 2.40 m long x 0.57 m deep. The tank is surrounded by a custom...fix two solid steel weights to eyehooks located at opposite poles of the shell. One eyehook is welded to the shell while the other is threaded in

  12. Identification of Spitzer-IRS staring mode targets in the Magellanic Clouds

    CERN Document Server

    Ruffle, Paul M E; Kemper, F

    2011-01-01

    The SAGE-LMC, SAGE-SMC and HERITAGE surveys have mapped the Magellanic Clouds in the infrared using the Spitzer and Herschel Space Telescopes. Over 8.5 million point sources were detected and catalogued in the LMC alone. Staring mode observations using the InfraRed Spectrograph (IRS) on board Spitzer have been obtained for 1,000 positions in the LMC and ~250 in the SMC. From the infrared spectroscopy we have identified the nature of the sources for which spectroscopy is available. These IRS staring mode targets represent an important contribution to the SED of these dwarf galaxies. Here we report on our latest results.

  13. Computational identification of putative miRNAs and their target genes in pathogenic amoeba Naegleria fowleri.

    Science.gov (United States)

    Padmashree, Dyavegowda; Swamy, Narayanaswamy Ramachandra

    2015-01-01

    Naegleria fowleri is a parasitic unicellular free living eukaryotic amoeba. The parasite spreads through contaminated water and causes primary amoebic meningoencephalitis (PAM). Therefore, it is of interest to understand its molecular pathogenesis. Hence, we analyzed the parasite genome for miRNAs (microRNAs) that are non-coding, single stranded RNA molecules. We identified 245 miRNAs using computational methods in N. fowleri, of which five miRNAs are conserved. The predicted miRNA targets were analyzed by using miRanda (software) and further studied the functions by subsequently annotating using AmiGo (a gene ontology web tool).

  14. An approach to identification and modelling of artificial grounds in urban area from multidisciplinary data (Oviedo, NW Spain)

    Science.gov (United States)

    Pando, Luis; Flor-Blanco, Germán; María Díaz-Díaz, Luis; Arias, Daniel

    2016-04-01

    This contribution describes the investigation of changes on urban relief caused by anthropogenic processes in Oviedo (population 215,000), the capital city of Asturias, formerly a Christian kingdom (719-925 AD) located in the north-western Iberian Peninsula. This city is placed on a Mesozoic-Cenozoic basin above a folded Paleozoic basement. Oviedo's subsurface is formed by carbonate and siliciclastic Cretaceous formations, and the overlying fluvial-lacustrine deposits of Paleogene age; the latter are mainly composed of marls, clays and gypsum layers. The urban core, which extends 15 km2, presents an elevation range between 160 to 330 m above mean sea level and the natural slopes reach up 15o in the built-up area. The research involved at first the collection and review of more than 950 borehole logs, presenting the man-made fills an average thickness of 1.9 m with maximum value of 25 m. Then topographic variations that occurred during the period of greatest urban development were analysed through map algebra. The data used to construct Digital Elevation Models (DEM) were provided by 1:5,000 city maps performed since 1869 to the present, all properly georeferenced. The subtraction operations generated Digital Terrain Models representing ground elevation gains and losses during different periods of time, after setting the necessary control points (elevation remains invariant) and corrections in order to avoid altitude deviations between DEMs. The thicknesses estimated for the man-made fills were compared with borehole data to validate the prediction, obtaining good correlations. The GIS-based methodology was complemented by an inspection of the historical evolution of land uses (i.e., using ancient street maps, aerial images interpretation and documentary references since the thirteenth century), and the analysis of all the surficial geological maps that have been published. Man-made grounds were then classified into categories, mainly: (i) earthworks related to

  15. Global Identification of EVI1 Target Genes in Acute Myeloid Leukemia.

    Directory of Open Access Journals (Sweden)

    Carolyn Glass

    Full Text Available The ecotropic virus integration site 1 (EVI1 transcription factor is associated with human myeloid malignancy of poor prognosis and is overexpressed in 8-10% of adult AML and strikingly up to 27% of pediatric MLL-rearranged leukemias. For the first time, we report comprehensive genomewide EVI1 binding and whole transcriptome gene deregulation in leukemic cells using a combination of ChIP-Seq and RNA-Seq expression profiling. We found disruption of terminal myeloid differentiation and cell cycle regulation to be prominent in EVI-induced leukemogenesis. Specifically, we identified EVI1 directly binds to and downregulates the master myeloid differentiation gene Cebpe and several of its downstream gene targets critical for terminal myeloid differentiation. We also found EVI1 binds to and downregulates Serpinb2 as well as numerous genes involved in the Jak-Stat signaling pathway. Finally, we identified decreased expression of several ATP-dependent P2X purinoreceptors genes involved in apoptosis mechanisms. These findings provide a foundation for future study of potential therapeutic gene targets for EVI1-induced leukemia.

  16. Identification of novel human damage response proteins targeted through yeast orthology.

    Directory of Open Access Journals (Sweden)

    J Peter Svensson

    Full Text Available Studies in Saccharomyces cerevisiae show that many proteins influence cellular survival upon exposure to DNA damaging agents. We hypothesized that human orthologs of these S. cerevisiae proteins would also be required for cellular survival after treatment with DNA damaging agents. For this purpose, human homologs of S. cerevisiae proteins were identified and mapped onto the human protein-protein interaction network. The resulting human network was highly modular and a series of selection rules were implemented to identify 45 candidates for human toxicity-modulating proteins. The corresponding transcripts were targeted by RNA interference in human cells. The cell lines with depleted target expression were challenged with three DNA damaging agents: the alkylating agents MMS and 4-NQO, and the oxidizing agent t-BuOOH. A comparison of the survival revealed that the majority (74% of proteins conferred either sensitivity or resistance. The identified human toxicity-modulating proteins represent a variety of biological functions: autophagy, chromatin modifications, RNA and protein metabolism, and telomere maintenance. Further studies revealed that MMS-induced autophagy increase the survival of cells treated with DNA damaging agents. In summary, we show that damage recovery proteins in humans can be identified through homology to S. cerevisiae and that many of the same pathways are represented among the toxicity modulators.

  17. Comprehensive identification of SUMO2/3 targets and their dynamics during mitosis.

    Science.gov (United States)

    Schou, Julie; Kelstrup, Christian D; Hayward, Daniel G; Olsen, Jesper V; Nilsson, Jakob

    2014-01-01

    During mitosis large alterations in cellular structures occur rapidly, which to a large extent is regulated by post-translational modification of proteins. Modification of proteins with the small ubiquitin-related protein SUMO2/3 regulates mitotic progression, but few mitotic targets have been identified so far. To deepen our understanding of SUMO2/3 during this window of the cell cycle, we undertook a comprehensive proteomic characterization of SUMO2/3 modified proteins in mitosis and upon mitotic exit. We developed an efficient tandem affinity purification strategy of SUMO2/3 modified proteins from mitotic cells. Combining this purification strategy with cell synchronization procedures and quantitative mass spectrometry allowed for the mapping of numerous novel targets and their dynamics as cells progressed out of mitosis. This identified RhoGDIα as a major SUMO2/3 modified protein, specifically during mitosis, mediated by the SUMO ligases PIAS2 and PIAS3. Our data provide a rich resource for further exploring the role of SUMO2/3 modifications in mitosis and cell cycle regulation.

  18. Global identification of genes targeted by DNMT3b for epigenetic silencing in lung cancer.

    Science.gov (United States)

    Teneng, I; Tellez, C S; Picchi, M A; Klinge, D M; Yingling, C M; Snider, A M; Liu, Y; Belinsky, S A

    2015-01-29

    The maintenance cytosine DNA methyltransferase DNMT1 and de novo methyltransferase DNMT3b cooperate to establish aberrant DNA methylation and chromatin complexes to repress gene transcription during cancer development. The expression of DNMT3b was constitutively increased 5-20-fold in hTERT/CDK4-immortalized human bronchial epithelial cells (HBECs) before treatment with low doses of tobacco carcinogens. Overexpression of DNMT3b increased and accelerated carcinogen-induced transformation. Genome-wide profiling of transformed HBECs identified 143 DNMT3b-target genes, many of which were transcriptionally regulated by the polycomb repressive complex 2 (PRC2) complex and silenced through aberrant methylation in non-small-cell lung cancer cell lines. Two genes studied in detail, MAL and OLIG2, were silenced during transformation, initially through enrichment for H3K27me3 and H3K9me2, commonly methylated in lung cancer, and exert tumor suppressor effects in vivo through modulating cancer-related pathways. Re-expression of MAL and OLIG2 to physiological levels dramatically reduced the growth of lung tumor xenografts. Our results identify a key role for DNMT3b in the earliest stages of initiation and provide a comprehensive catalog of genes targeted for silencing by this methyltransferase in non-small-cell lung cancer.

  19. Identification of conserved microRNAs and their targets in the model legume Lotus japonicus.

    Science.gov (United States)

    Hu, Jihong; Zhang, Hongyuan; Ding, Yi

    2013-04-15

    MicroRNAs (miRNAs) are a new class of non-protein coding small RNAs that regulate gene expression at the post-transcriptional level in plants and animals. Although thousands of miRNAs were identified in many plant species, only 3 miRNAs have been reported in Lotus Japonicus, a model legume plant. In this study, 80 potential miRNA candidates were identified in 28 ESTs and 52 GSSs of L. japonicus using a homology-based computational analysis. A total of 735 miRNA targets were predicted and some of them encoded transcription factors as well as genes that function in stress response, signal transduction, methylation and others. Quantitative real-time PCR (qRT-PCR) analysis indicated that miR156a, miR160a and miR399a participated in seed germination of L. japonicus. GO and KEGG analysis suggested that the predicted miRNAs might target genes involved in lipid, nitrogen, starch sucrose metabolism and signal transduction.

  20. Identification of estrogen receptor-related receptor gamma as a direct transcriptional target of angiogenin.

    Directory of Open Access Journals (Sweden)

    Jian Ang

    Full Text Available Nuclear translocation of angiogenin (ANG is essential for the proliferation of its target cells. ANG promotes rRNA synthesis, while whether it regulates mRNA transcription remains unknown. Using the chromatin immunoprecipitation method, we have identified 12 ANG-binding sequences. One of these sequences lies in the estrogen receptor-related receptor gamma (ERRγ gene which we designated as ANG-Binding Sequence within ERRγ (ABSE. ABSE exhibited ANG-dependent repressor activity in the luciferase reporter system. Down-regulation of ANG increased ERRγ expression, and active gene marker level at the ABSE region. The expression levels of ERRγ targets genes, p21(WAF/CIP and p27(KIP1, and the occupation of ERRγ on their promoter regions were increased in ANG-deficient cells accordingly. Furthermore, knockdown of ERRγ promoted the proliferation rate in ANG-deficient breast cancer cells. Finally, immunohistochemistry staining showed negative correlation between ANG and ERRγ in breast cancer tissue. Altogether, our study provides evidence that nuclear ANG directly binds to the ABSE of ERRγ gene and inhibits ERRγ transcription to promote breast cancer cell proliferation.

  1. Computational identification of citrus microRNAs and target analysis in citrus expressed sequence tags.

    Science.gov (United States)

    Song, C; Jia, Q; Fang, J; Li, F; Wang, C; Zhang, Z

    2010-11-01

    MicroRNAs (miRNAs) are a new family of small RNA molecules found in plants and animals. We developed a comprehensive strategy for identifying new miRNA homologues by mining the repository of available citrus expressed sequence tags (ESTs). By adopting a range of filtering criteria, we identified a total of 38 potential miRNAs--nine, five, nine and 15 miRNAs in Citrus trifoliata (ctr-miRNAs), C. clementina (ccl-miRNAs), C. reticulata (crt-miRNAs) and C. sinensis (csi-miRNAs), respectively--from more than 430,000 EST sequences in citrus. Using the potential miRNA sequences, we conducted a further BLAST search of the mRNA database and found six potential target genes in these citrus species. Eight miRNAs were selected in order to verify their existence in citrus using Northern blotting, and the functions of several miRNAs in miRNA-mediated gene regulation are experimentally suggested. It appears that all these miRNAs regulate expression of their target genes by cleavage, which is the most common situation in gene regulation mediated by plant miRNAs. Our achievement in identifying new miRNAs in citrus provides a powerful incentive for further studies on the important roles of these miRNAs.

  2. Identification of a New Class of Antifungals Targeting the Synthesis of Fungal Sphingolipids

    Science.gov (United States)

    Mor, Visesato; Rella, Antonella; Farnoud, Amir M.; Singh, Ashutosh; Munshi, Mansa; Bryan, Arielle; Naseem, Shamoon; Konopka, James B.; Ojima, Iwao; Bullesbach, Erika; Ashbaugh, Alan; Linke, Michael J.; Cushion, Melanie; Collins, Margaret; Ananthula, Hari Krishna; Sallans, Larry; Desai, Pankaj B.; Wiederhold, Nathan P.; Fothergill, Annette W.; Kirkpatrick, William R.; Patterson, Thomas; Wong, Lai Hong; Sinha, Sunita; Giaever, Guri; Nislow, Corey; Flaherty, Patrick; Pan, Xuewen; Cesar, Gabriele Vargas; de Melo Tavares, Patricia; Frases, Susana; Miranda, Kildare; Rodrigues, Marcio L.; Luberto, Chiara; Nimrichter, Leonardo

    2015-01-01

    ABSTRACT Recent estimates suggest that >300 million people are afflicted by serious fungal infections worldwide. Current antifungal drugs are static and toxic and/or have a narrow spectrum of activity. Thus, there is an urgent need for the development of new antifungal drugs. The fungal sphingolipid glucosylceramide (GlcCer) is critical in promoting virulence of a variety of human-pathogenic fungi. In this study, we screened a synthetic drug library for compounds that target the synthesis of fungal, but not mammalian, GlcCer and found two compounds [N′-(3-bromo-4-hydroxybenzylidene)-2-methylbenzohydrazide (BHBM) and its derivative, 3-bromo-N′-(3-bromo-4-hydroxybenzylidene) benzohydrazide (D0)] that were highly effective in vitro and in vivo against several pathogenic fungi. BHBM and D0 were well tolerated in animals and are highly synergistic or additive to current antifungals. BHBM and D0 significantly affected fungal cell morphology and resulted in the accumulation of intracellular vesicles. Deep-sequencing analysis of drug-resistant mutants revealed that four protein products, encoded by genes APL5, COS111, MKK1, and STE2, which are involved in vesicular transport and cell cycle progression, are targeted by BHBM. PMID:26106079

  3. Rapid Identification of Coumarins from Micromelum falcatum by UPLC-HRMS/MS and Targeted Isolation of Three New Derivatives

    Directory of Open Access Journals (Sweden)

    Eirini Kouloura

    2014-09-01

    Full Text Available Micromelum falcatum, a medicinal plant of the Rutaceae family, has been used in the Traditional Chinese Medicine (TCM mainly against colds and rheumatoid arthritis. Despite its traditional use the association of its constituents with possible anti-inflammatory activity has not been explored. During this study, a rapid UPLC-ESI(+-HRMS method was developed for the profiling of M. falcatum leave extracts and the targeted isolation of coumarin constituents. Based on chromatographic, spectroscopic and spectrometric features several 7-oxygenated coumarin derivatives were detected. After targeted isolation, eight coumarins, among them three new natural products, namely microfalcrin, microcoumaririn and micromelosidester, were purified using semi-preparative HPLC and unambiguously identified by 1 and 2D NMR. Furthermore, important spectrometric characteristics were revealed based on the HRMS and HRMS/MS spectra of the isolated 7-oxygenated coumarins facilitating their identification in complex mixtures. Finally, the anti-inflammatory properties of the extracts and representative compounds were evaluated by measuring the inhibition of the pro-inflammatory mediator NF-κB induction and nitric oxide (NO production.

  4. Global gene expression profiling of human pleural mesotheliomas: identification of matrix metalloproteinase 14 (MMP-14 as potential tumour target.

    Directory of Open Access Journals (Sweden)

    Stefania Crispi

    Full Text Available BACKGROUND: The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. METHODOLOGY: We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002. CONCLUSIONS: Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma.

  5. Global Gene Expression Profiling Of Human Pleural Mesotheliomas: Identification of Matrix Metalloproteinase 14 (MMP-14) as Potential Tumour Target

    Science.gov (United States)

    Crispi, Stefania; Calogero, Raffaele A.; Santini, Mario; Mellone, Pasquale; Vincenzi, Bruno; Citro, Gennaro; Vicidomini, Giovanni; Fasano, Silvia; Meccariello, Rosaria; Cobellis, Gilda; Menegozzo, Simona; Pierantoni, Riccardo; Facciolo, Francesco; Baldi, Alfonso; Menegozzo, Massimo

    2009-01-01

    Background The goal of our study was to molecularly dissect mesothelioma tumour pathways by mean of microarray technologies in order to identify new tumour biomarkers that could be used as early diagnostic markers and possibly as specific molecular therapeutic targets. Methodology We performed Affymetrix HGU133A plus 2.0 microarray analysis, containing probes for about 39,000 human transcripts, comparing 9 human pleural mesotheliomas with 4 normal pleural specimens. Stringent statistical feature selection detected a set of differentially expressed genes that have been further evaluated to identify potential biomarkers to be used in early diagnostics. Selected genes were confirmed by RT-PCR. As reported by other mesothelioma profiling studies, most of genes are involved in G2/M transition. Our list contains several genes previously described as prognostic classifier. Furthermore, we found novel genes, never associated before to mesotheliom that could be involved in tumour progression. Notable is the identification of MMP-14, a member of matrix metalloproteinase family. In a cohort of 70 mesothelioma patients, we found by a multivariate Cox regression analysis, that the only parameter influencing overall survival was expression of MMP14. The calculated relative risk of death in MM patients with low MMP14 expression was significantly lower than patients with high MMp14 expression (P = 0.002). Conclusions Based on the results provided, this molecule could be viewed as a new and effective therapeutic target to test for the cure of mesothelioma. PMID:19753302

  6. Identification of novel targets for breast cancer by exploring gene switches on a genome scale

    Directory of Open Access Journals (Sweden)

    Wu Ming

    2011-11-01

    Full Text Available Abstract Background An important feature that emerges from analyzing gene regulatory networks is the "switch-like behavior" or "bistability", a dynamic feature of a particular gene to preferentially toggle between two steady-states. The state of gene switches plays pivotal roles in cell fate decision, but identifying switches has been difficult. Therefore a challenge confronting the field is to be able to systematically identify gene switches. Results We propose a top-down mining approach to exploring gene switches on a genome-scale level. Theoretical analysis, proof-of-concept examples, and experimental studies demonstrate the ability of our mining approach to identify bistable genes by sampling across a variety of different conditions. Applying the approach to human breast cancer data identified genes that show bimodality within the cancer samples, such as estrogen receptor (ER and ERBB2, as well as genes that show bimodality between cancer and non-cancer samples, where tumor-associated calcium signal transducer 2 (TACSTD2 is uncovered. We further suggest a likely transcription factor that regulates TACSTD2. Conclusions Our mining approach demonstrates that one can capitalize on genome-wide expression profiling to capture dynamic properties of a complex network. To the best of our knowledge, this is the first attempt in applying mining approaches to explore gene switches on a genome-scale, and the identification of TACSTD2 demonstrates that single cell-level bistability can be predicted from microarray data. Experimental confirmation of the computational results suggest TACSTD2 could be a potential biomarker and attractive candidate for drug therapy against both ER+ and ER- subtypes of breast cancer, including the triple negative subtype.

  7. Identification of STAT5A and STAT5B target genes in human T cells.

    Directory of Open Access Journals (Sweden)

    Takahiro Kanai

    Full Text Available Signal transducer and activator of transcription (STAT comprises a family of universal transcription factors that help cells sense and respond to environmental signals. STAT5 refers to two highly related proteins, STAT5A and STAT5B, with critical function: their complete deficiency is lethal in mice; in humans, STAT5B deficiency alone leads to endocrine and immunological problems, while STAT5A deficiency has not been reported. STAT5A and STAT5B show peptide sequence similarities greater than 90%, but subtle structural differences suggest possible non-redundant roles in gene regulation. However, these roles remain unclear in humans. We applied chromatin immunoprecipitation followed by DNA sequencing using human CD4(+ T cells to detect candidate genes regulated by STAT5A and/or STAT5B, and quantitative-PCR in STAT5A or STAT5B knock-down (KD human CD4(+ T cells to validate the findings. Our data show STAT5A and STAT5B play redundant roles in cell proliferation and apoptosis via SGK1 interaction. Interestingly, we found a novel, unique role for STAT5A in binding to genes involved in neural development and function (NDRG1, DNAJC6, and SSH2, while STAT5B appears to play a distinct role in T cell development and function via DOCK8, SNX9, FOXP3 and IL2RA binding. Our results also suggest that one or more co-activators for STAT5A and/or STAT5B may play important roles in establishing different binding abilities and gene regulation behaviors. The new identification of these genes regulated by STAT5A and/or STAT5B has major implications for understanding the pathophysiology of cancer progression, neural disorders, and immune abnormalities.

  8. Feature extraction for target identification and image classification of OMIS hyperspectral image

    Institute of Scientific and Technical Information of China (English)

    DU Pei-jun; TAN Kun; SU Hong-jun

    2009-01-01

    In order to combine feature extraction operations with specific hyperspectrai remote sensing information processing objectives, two aspects of feature extraction were explored. Based on clustering and decision tree algorithm, spectral absorption index (SAI), continuum-removal and derivative spectral analysis were employed to discover characterized spectral features of dif-ferent targets, and decision trees for identifying a specific class and discriminating different classes were generated. By combining support vector machine (SVM) classifier with different feature extraction strategies including principal component analysis (PCA), minimum noise fraction (MNF), grouping PCA, and derivate spectral analysis, the performance of feature extraction approaches in classification was evaluated. The results show that feature extraction by PCA and derivate spectral analysis are effective to OMIS (operational modular imaging spectrometer) image classification using SVM, and SVM outperforms traditional SAM and MLC classifiers for OMIS data.

  9. Identification of conserved microRNAs and their targets in chickpea (Cicer arietinum L.).

    Science.gov (United States)

    Hu, Jihong; Sun, Lulu; Ding, Yi

    2013-04-01

    The microRNAs (miRNAs) are a new class of non-protein coding small RNAs that regulate gene expression at the post-transcriptional level in plants. Although thousands of miRNAs have been identified in many plant species, little studies have been reported about chickpea microRNAs. In this study, 28 potential miRNA candidates belonging to 20 families were identified from 16 ESTs and 12 GSSs in chickpea using a comparative genome-based computational analysis. A total of 664 miRNA targets were predicted and some of them encoded transcription factors as well as genes that function in stress response, signal transduction, methylation and a variety of other metabolic processes. These findings lay the foundation for further understanding of miRNA function in the development of chickpea.

  10. Reducing impaired driving through the identification of Repeat Target Vehicles: A case study.

    Science.gov (United States)

    Stewart, James

    2012-02-01

    One of the most persistent groups of impaired drivers that are seemingly unaffected by social pressure, moral appeals, and the fear of arrest is that of the repeat impaired driver. This smaller group accounts for a disproportionate number of all impaired driving trips, often with high blood alcohol contents. New approaches are needed to identify and deal with the repeat impaired driver. We propose a method based on the discovery that almost 10% of all impaired driving calls for service involve repeat vehicles. Using the number of times a vehicle appears in our data, the average time to repeat, and the personality characteristics of the repeat impaired driver, we are able to create a comprehensive and predictive description of a Repeat Target Vehicle (RTV). Our method provides an opportunity to explore new and innovative crime reduction strategies that were never before possible. Copyright © 2011 Elsevier Ltd. All rights reserved.

  11. Identification and analysis of miRNAs and their targets in ginger using bioinformatics approach.

    Science.gov (United States)

    Singh, Noopur; Srivastava, Swati; Sharma, Ashok

    2016-01-10

    MicroRNAs (miRNAs) are a large family of endogenous small RNAs derived from the non-protein coding genes. miRNA regulates the gene expression at the post-transcriptional level and plays an important role in plant development. Zingiber officinale is an important medicinal plant having numerous therapeutic properties. Its bioactive compound gingerol and essential oil posses important pharmacological and physiological activities. In this study, we used a homology search based computational approach for identifying miRNAs in Z. officinale. A total of 16 potential miRNA families (miR167, miR407, miR414, miR5015, miR5021, miR5644, miR5645, miR5656, miR5658, miR5664, miR827, miR838, miR847, miR854, miR862 and miR864) were predicted in ginger. Phylogenetic and conserved analyses were performed for predicted miRNAs. Thirteen miRNA families were found to regulate 300 target transcripts and play an important role in cell signaling, reproduction, metabolic process and stress. To understand the miRNA mediated gene regulatory control and to validate miRNA target predictions, a biological network was also constructed. Gene ontology and pathway analyses were also done. miR5015 was observed to regulate the biosynthesis of gingerol by inhibiting phenyl ammonia lyase (PAL), a precursor enzyme in the biosynthesis of gingerol. Our results revealed that most of the predicted miRNAs were involved in the regulation of rhizome development. miR5021, miR854 and miR838 were identified to regulate the rhizome development and the essential oil biosynthesis in ginger. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Identification and target prediction of miRNAs specifically expressed in rat neural tissue

    Directory of Open Access Journals (Sweden)

    Tu Kang

    2009-05-01

    Full Text Available Abstract Background MicroRNAs (miRNAs are a large group of RNAs that play important roles in regulating gene expression and protein translation. Several studies have indicated that some miRNAs are specifically expressed in human, mouse and zebrafish tissues. For example, miR-1 and miR-133 are specifically expressed in muscles. Tissue-specific miRNAs may have particular functions. Although previous studies have reported the presence of human, mouse and zebrafish tissue-specific miRNAs, there have been no detailed reports of rat tissue-specific miRNAs. In this study, Home-made rat miRNA microarrays which established in our previous study were used to investigate rat neural tissue-specific miRNAs, and mapped their target genes in rat tissues. This study will provide information for the functional analysis of these miRNAs. Results In order to obtain as complete a picture of specific miRNA expression in rat neural tissues as possible, customized miRNA microarrays with 152 selected miRNAs from miRBase were used to detect miRNA expression in 14 rat tissues. After a general clustering analysis, 14 rat tissues could be clearly classified into neural and non-neural tissues based on the obtained expression profiles with p values Conclusion Our work provides a global view of rat neural tissue-specific miRNA profiles and a target map of miRNAs, which is expected to contribute to future investigations of miRNA regulatory mechanisms in neural systems.

  13. Identification of estrogen target genes during zebrafish embryonic development through transcriptomic analysis.

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    Ruixin Hao

    Full Text Available Estrogen signaling is important for vertebrate embryonic development. Here we have used zebrafish (Danio rerio as a vertebrate model to analyze estrogen signaling during development. Zebrafish embryos were exposed to 1 µM 17β-estradiol (E2 or vehicle from 3 hours to 4 days post fertilization (dpf, harvested at 1, 2, 3 and 4 dpf, and subjected to RNA extraction for transcriptome analysis using microarrays. Differentially expressed genes by E2-treatment were analyzed with hierarchical clustering followed by biological process and tissue enrichment analysis. Markedly distinct sets of genes were up and down-regulated by E2 at the four different time points. Among these genes, only the well-known estrogenic marker vtg1 was co-regulated at all time points. Despite this, the biological functional categories targeted by E2 were relatively similar throughout zebrafish development. According to knowledge-based tissue enrichment, estrogen responsive genes were clustered mainly in the liver, pancreas and brain. This was in line with the developmental dynamics of estrogen-target tissues that were visualized using transgenic zebrafish containing estrogen responsive elements driving the expression of GFP (Tg(5xERE:GFP. Finally, the identified embryonic estrogen-responsive genes were compared to already published estrogen-responsive genes identified in male adult zebrafish (Gene Expression Omnibus database. The expressions of a few genes were co-regulated by E2 in both embryonic and adult zebrafish. These could potentially be used as estrogenic biomarkers for exposure to estrogens or estrogenic endocrine disruptors in zebrafish. In conclusion, our data suggests that estrogen effects on early embryonic zebrafish development are stage- and tissue- specific.

  14. Identification of proteins involved in neural progenitor cell targeting of gliomas

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    Honeth Gabriella

    2009-06-01

    Full Text Available Abstract Background Glioblastoma are highly aggressive tumors with an average survival time of 12 months with currently available treatment. We have previously shown that specific embryonic neural progenitor cells (NPC have the potential to target glioma growth in the CNS of rats. The neural progenitor cell treatment can cure approximately 40% of the animals with malignant gliomas with no trace of a tumor burden 6 months after finishing the experiment. Furthermore, the NPCs have been shown to respond to signals from the tumor environment resulting in specific migration towards the tumor. Based on these results we wanted to investigate what factors could influence the growth and progression of gliomas in our rodent model. Methods Using microarrays we screened for candidate genes involved in the functional mechanism of tumor inhibition by comparing glioma cell lines to neural progenitor cells with or without anti-tumor activity. The expression of candidate genes was confirmed at RNA level by quantitative RT-PCR and at the protein level by Western blots and immunocytochemistry. Moreover, we have developed in vitro assays to mimic the antitumor effect seen in vivo. Results We identified several targets involved in glioma growth and migration, specifically CXCL1, CD81, TPT1, Gas6 and AXL proteins. We further showed that follistatin secretion from the NPC has the potential to decrease tumor proliferation. In vitro co-cultures of NPC and tumor cells resulted in the inhibition of tumor growth. The addition of antibodies against proteins selected by gene and protein expression analysis either increased or decreased the proliferation rate of the glioma cell lines in vitro. Conclusion These results suggest that these identified factors might be useful starting points for performing future experiments directed towards a potential therapy against malignant gliomas.

  15. Identification of nuclear protein targets for six leukemogenic tyrosine kinases governed by post-translational regulation.

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    Andrew Pierce

    Full Text Available Mutated tyrosine kinases are associated with a number of different haematological malignancies including myeloproliferative disorders, lymphoma and acute myeloid leukaemia. The potential commonalities in the action of six of these leukemogenic proteins on nuclear proteins were investigated using systematic proteomic analysis. The effects on over 3600 nuclear proteins and 1500 phosphopeptide sites were relatively quantified in seven isogenic cell lines. The effects of the kinases were diverse although some commonalities were found. Comparison of the nuclear proteomic data with transcriptome data and cytoplasmic proteomic data indicated that the major changes are due to post-translational mechanisms rather than changes in mRNA or protein distribution. Analysis of the promoter regions of genes whose protein levels changed in response to the kinases showed the most common binding site found was that for NFκB whilst other sites such as those for the glucocorticoid receptor were also found. Glucocorticoid receptor levels and phosphorylation were decreased by all 6 PTKs. Whilst Glucocorticoid receptor action can potentiate NFκB action those proteins where genes have NFκB binding sites were in often regulated post-translationally. However all 6 PTKs showed evidence of NFkB pathway modulation via activation via altered IkB and NFKB levels. Validation of a common change was also undertaken with PMS2, a DNA mismatch repair protein. PMS2 nuclear levels were decreased in response to the expression of all 6 kinases, with no concomitant change in mRNA level or cytosolic protein level. Response to thioguanine, that requires the mismatch repair pathway, was modulated by all 6 oncogenic kinases. In summary common targets for 6 oncogenic PTKs have been found that are regulated by post-translational mechanisms. They represent potential new avenues for therapies but also demonstrate the post-translational regulation is a key target of leukaemogenic kinases.

  16. Identification and Characterization of a Chloroplast-Targeted Obg GTPase in Dendrobium officinale.

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    Chen, Ji; Deng, Feng; Deng, Mengsheng; Han, Jincheng; Chen, Jianbin; Wang, Li; Yan, Shen; Tong, Kai; Liu, Fan; Tian, Mengliang

    2016-12-01

    Bacterial homologous chloroplast-targeted Obg GTPases (ObgCs) belong to the plant-typical Obg group, which is involved in diverse physiological processes during chloroplast development. However, the evolutionarily conserved function of ObgC in plants remains elusive and requires further investigation. In this study, we identified DoObgC from an epiphytic plant Dendrobium officinale and demonstrated the characteristics of DoObgC. Sequence analysis indicated that DoObgC is highly conserved with other plant ObgCs, which contain the chloroplast transit peptide (cTP), Obg fold, G domain, and OCT regions. The C terminus of DoObgC lacking the chloroplast-targeting cTP region, DoObgCΔ1-160, showed strong similarity to ObgE and other bacterial Obgs. Overexpression of DoObgCΔ1-160 in Escherichia coli caused slow cell growth and an increased number of elongated cells. This phenotype was consistent with the phenotype of cells overexpressing ObgE. Furthermore, the expression of recombinant DoObgCΔ1-160 enhanced the cell persistence of E. coli to streptomycin. Results of transient expression assays revealed that DoObgC was localized to chloroplasts. Moreover, we demonstrated that DoObgC could rescue the embryotic lethal phenotype of the Arabidopsis obgc-t mutant, suggesting that DoObgC is a functional homolog to Arabidopsis AtObgC in D. officinale. Gene expression profiles showed that DoObgC was expressed in leaf-specific and light-dependent patterns and that DoObgC responded to wounding treatments. Our previous and present studies reveal that ObgC has an evolutionarily conserved role in ribosome biogenesis to adapt chloroplast development to the environment.

  17. Propagation of tau pathology in Alzheimer's disease: identification of novel therapeutic targets.

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    Pooler, Amy M; Polydoro, Manuela; Wegmann, Susanne; Nicholls, Samantha B; Spires-Jones, Tara L; Hyman, Bradley T

    2013-01-01

    Accumulation and aggregation of the microtubule-associated protein tau are a pathological hallmark of neurodegenerative disorders such as Alzheimer's disease (AD). In AD, tau becomes abnormally phosphorylated and forms inclusions throughout the brain, starting in the entorhinal cortex and progressively affecting additional brain regions as the disease progresses. Formation of these inclusions is thought to lead to synapse loss and cell death. Tau is also found in the cerebrospinal fluid (CSF), and elevated levels are a biomarker for AD. Until recently, it was thought that the presence of tau in the CSF was due to the passive release of aggregated tau from dead or dying tangle-bearing neurons. However, accumulating evidence from different AD model systems suggests that tau is actively secreted and transferred between synaptically connected neurons. Transgenic mouse lines with localized expression of aggregating human tau in the entorhinal cortex have demonstrated that, as these animals age, tau becomes mislocalized from axons to cell bodies and dendrites and that human tau-positive aggregates form first in the entorhinal cortex and later in downstream projection targets. Numerous in vitro and in vivo studies have provided insight into the mechanisms by which tau may be released and internalized by neurons and have started to provide insight into how tau pathology may spread in AD. In this review, we discuss the evidence for regulated tau release and its specific uptake by neurons. Furthermore, we identify possible therapeutic targets for preventing the propagation of tau pathology, as inhibition of tau transfer may restrict development of tau tangles in a small subset of neurons affected in early stages of AD and therefore prevent widespread neuron loss and cognitive dysfunction associated with later stages of the disease.

  18. Chemogenomic identification of Ref-1/AP-1 as a therapeutic target for asthma.

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    Nguyen, Cu; Teo, Jia-Ling; Matsuda, Akihisa; Eguchi, Masakatsu; Chi, Emil Y; Henderson, William R; Kahn, Michael

    2003-02-04

    Asthma is characterized by an oxidantantioxidant imbalance in the lungs leading to activation of redox-sensitive transcription factors, nuclear factor kappaB (NF-kappaB), and activator protein-1 (AP-1). To develop therapeutic strategies for asthma, we used a chemogenomics approach to screen for small molecule inhibitor(s) of AP-1 transcription. We developed a beta-strand mimetic template that acts as a reversible inhibitor (pseudosubstrate) of redox proteins. This template incorporates an enedione moiety to trap reactive cysteine nucleophiles in the active sites of redox proteins. Specificity for individual redox factors was achieved through variations in X and Y functionality by using a combinatorial library approach. A limited array (2 x 6) was constructed where X was either NHCH(3) or NHCH(2) Ph and Y was methyl, phenyl, m-cyanophenyl, m-nitrophenyl, m-acetylaniline, or m-methylbenzoate. These analogs were evaluated for their ability to inhibit transcription in transiently transfected human lung epithelial A549 cells from either an AP-1 or NF-kappaB reporter. A small-molecule inhibitor, PNRI-299, was identified that selectively inhibited AP-1 transcription (IC(50) of 20 microM) without affecting NF-kappaB transcription (up to 200 microM) or thioredoxin (up to 200 microM). The molecular target of PNRI-299 was determined to be the oxidoreductase, redox effector factor-1 by an affinity chromatography approach. The selective redox effector factor-1 inhibitor, PNRI-299, significantly reduced airway eosinophil infiltration, mucus hypersecretion, edema, and IL-4 levels in a mouse asthma model. These data validate AP-1 as an important therapeutic target in allergic airway inflammation.

  19. Identification of Arx targets unveils new candidates for controlling cortical interneuron migration and differentiation

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    Gaelle M Friocourt

    2011-12-01

    Full Text Available Mutations in the homeobox transcription factor ARX have been found to be responsible for a wide spectrum of disorders extending from phenotypes with severe neuronal migration defects, such as lissencephaly, to mild forms of intellectual disabilities without apparent brain abnormalities, but with associated features of dystonia and epilepsy. Arx expression is mainly restricted to populations of GABA-containing neurons. Studies of the effects of ARX loss of function, either in humans or mutant mice, revealed varying defects, suggesting multiple roles of this gene in brain patterning, neuronal proliferation and migration, cell maturation and differentiation, as well as axonal outgrowth and connectivity. However, to date, little is known about how Arx functions as a transcription factor or which genes it binds and regulates. Recently, we combined chromatin immunoprecipitation and mRNA expression with microarray analysis and identified approximately 1000 gene promoters bound by Arx in transfected neuroblastoma N2a cells and mouse embryonic brain. To narrow the analysis of Arx targets to those most likely to control cortical interneuron migration and/or differentiation, we compare here our data to previously published studies searching for genes enriched or down-regulated in cortical interneurons between E13.5 and E15.5. We thus identified 14 Arx-target genes enriched (Cxcr7, Meis1, Ppap2a, Slc12a5, Ets2, Phlda1, Zif268, Igf1, Lmo3, Sema6, Lgi1, Alk, Tgfb3, Napb and 5 genes specifically down-regulated (Hmgn3, Lmo1, Ebf3, Rasgef1b and Slit2 in cortical migrating neurons. In this review, we present these genes and discuss how their possible regulation by Arx may lead to the dysfunction of GABAergic neurons, resulting in mental retardation and epilepsy.

  20. Endogenous occurrence of protein S-guanylation in Escherichia coli: Target identification and genetic regulation.

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    Tsutsuki, Hiroyasu; Jung, Minkyung; Zhang, Tianli; Ono, Katsuhiko; Ida, Tomoaki; Kunieda, Kohei; Ihara, Hideshi; Akaike, Takaaki; Sawa, Tomohiro

    2016-09-09

    8-Nitroguanosine 3',5'-cyclic monophosphate (8-nitro-cGMP) is a nitrated cGMP derivative formed in response to nitric oxide (NO) and reactive oxygen species (ROS). It can cause a post-translational modification (PTM) of protein thiols through cGMP adduction (protein S-guanylation). Accumulating evidence has suggested that, in mammals, S-guanylation of redox-sensor proteins may implicate in regulation of adaptive responses against ROS-associated oxidative stress. Occurrence as well as protein targets of S-guanylation in bacteria remained unknown, however. Here we demonstrated, for the first time, the endogenous occurrence of protein S-guanylation in Escherichia coli (E. coli). Western blotting using anti-S-guanylation antibody clearly showed that multiple proteins were S-guanylated in E. coli. Interestingly, some of those proteins were more intensely S-guanylated when bacteria were cultured under static culture condition than shaking culture condition. It has been known that E. coli is deficient of guanylate cyclase, an enzyme indispensable for 8-nitro-cGMP formation in mammals. We found that adenylate cyclase from E. coli potentially catalyzed 8-nitro-cGMP formation from its precursor 8-nitroguanosine 5'-triphosphate. More importantly, E. coli lacking adenylate cyclase showed significantly reduced formation of S-guanylated proteins. Our S-guanylation proteomics successfully identified S-guanylation protein targets in E. coli, including chaperons, ribosomal proteins, and enzymes which associate with protein synthesis, redox regulation and metabolism. Understanding of functional impacts for protein S-guanylation in bacterial signal transduction is necessary basis for development of potential chemotherapy and new diagnostic strategy for control of pathogenic bacterial infections.

  1. Identification of potential inhibitors for oncogenic target of dihydroorotate dehydrogenase using in silico approaches

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    Surekha, Kanagarajan; Nachiappan, Mutharasappan; Prabhu, Dhamodharan; Choubey, Sanjay Kumar; Biswal, Jayashree; Jeyakanthan, Jeyaraman

    2017-01-01

    Dihydroorotate dehydrogenase (DHODH) plays a major role in the rate limiting step of de novo pyrimidine biosynthesis pathway and it is pronounced as a novel target for drug development of cancer. The currently available drugs against DHODH are ineffective and bear various side effects. Three-dimensional structure of the targeted protein was constructed using molecular modeling approach followed by 100 ns molecular dynamics simulations. In this study, High Throughput Virtual Screening (HTVS) was performed using various compound libraries to identify pharmacologically potential molecules. The top four identified lead molecules includes NCI_47074, HitFinder_7630, Binding_66981 and Specs_108872 with high docking score of -9.45, -8.29, -8.04 and -8.03 kcal/mol and the corresponding binding free energy were -16.25, -56.37, -26.93 and -48.04 kcal/mol respectively. Arg122, Arg185, Glu255 and Gly257 are the key residues found to be interacting with the ligands. Molecular dynamics simulations of DHODH-inhibitors complexes were performed to assess the stability of various conformations from complex structures of TtDHODH. Furthermore, stereoelectronic features of the ligands were explored to facilitate charge transfer during the protein-ligand interactions using Density Functional Theoretical approach. Based on in silico analysis, the ligand NCI_47074 ((2Z)-3-({6-[(2Z)-3-carboxylatoprop-2-enamido]pyridin-2-yl}carbamoyl)prop-2-enoate) was found to be the most potent lead molecule which was validated using energetic and electronic parameters and it could serve as a template for designing effective anticancerous drug molecule.

  2. Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a New Anti-Mycobacterium Tuberculosis Target.

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    Meng, Jianzhou; Yang, Yanhui; Xiao, Chunling; Guan, Yan; Hao, Xueqin; Deng, Qi; Lu, Zhongyang

    2015-09-30

    Aspartic acid semialdehyde dehydrogenase (ASADH) lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. Mutations in the asadh gene encoding ASADH produce an inactive enzyme, which is lethal. Therefore, in this study, we investigated the hypothesis that ASADH represents a new anti-Mycobacterium tuberculosis (MTB) target. An asadh promoter-replacement mutant MTB, designated MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was constructed to investigate the physiological functions of ASADH in the host bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression was analyzed by Western blotting. The results showed that the growth and survival of MTB::asadh was completely inhibited in the absence of the inducer pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on the presence of the inducer in the medium. The starved mutant exhibited a marked reduction (approximately 80%) in the cell wall materials compared to the wild-type, in addition to obvious morphological differences that were apparent in scanning electron microscopy studies; however, with the addition of pristinamycin, the cell wall contents and morphology similar to those of the wild-type strain were recovered. The starved mutant also exhibited almost no pathogenicity in an in vitro model of infection using mouse macrophage J774A.1 cells. The mutant showed a concentration-dependent recovery of pathogenicity with the addition of the inducer. These findings implicate ASADH as a promising target for the development of novel anti-MTB drugs.

  3. Identification and Validation of Aspartic Acid Semialdehyde Dehydrogenase as a New Anti-Mycobacterium Tuberculosis Target

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    Jianzhou Meng

    2015-09-01

    Full Text Available Aspartic acid semialdehyde dehydrogenase (ASADH lies at the first branch point in the essential aspartic acid biosynthetic pathway that is found in bacteria and plants but is absent from animals. Mutations in the asadh gene encoding ASADH produce an inactive enzyme, which is lethal. Therefore, in this study, we investigated the hypothesis that ASADH represents a new anti-Mycobacterium tuberculosis (MTB target. An asadh promoter-replacement mutant MTB, designated MTB::asadh, in which asadh gene expression is regulated by pristinamycin, was constructed to investigate the physiological functions of ASADH in the host bacteria. Bacterial growth was evaluated by monitoring OD600 and ASADH expression was analyzed by Western blotting. The results showed that the growth and survival of MTB::asadh was completely inhibited in the absence of the inducer pristinamycin. Furthermore, the growth of the mutant was rigorously dependent on the presence of the inducer in the medium. The starved mutant exhibited a marked reduction (approximately 80% in the cell wall materials compared to the wild-type, in addition to obvious morphological differences that were apparent in scanning electron microscopy studies; however, with the addition of pristinamycin, the cell wall contents and morphology similar to those of the wild-type strain were recovered. The starved mutant also exhibited almost no pathogenicity in an in vitro model of infection using mouse macrophage J774A.1 cells. The mutant showed a concentration-dependent recovery of pathogenicity with the addition of the inducer. These findings implicate ASADH as a promising target for the development of novel anti-MTB drugs.

  4. Identification of an aptamer through whole cell-SELEX for targeting high metastatic liver cancers.

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    Rong, Yuan; Chen, Hao; Zhou, Xue-Feng; Yin, Chang-Qing; Wang, Bi-Cheng; Peng, Chun-Wei; Liu, Shao-Ping; Wang, Fu-Bing

    2016-02-16

    Hepatocellular carcinoma (HCC) is one of the most deadly human cancers due to its ability of invasion and metastasis. Thus, the approaches to identify potential compounds that inhibit invasion and metastasis of HCC are critical for treatment of this disease. In the present study, we used HCCLM9 cells with high metastatic potential and MHCC97L with low metastatic potential as a model system to study the molecular mechanisms of HCC metastasis. By applying cell- Systematic Evolution of Ligands by Exponential enrichment (SELEX) against living cells, we used HCCLM9 as target cells and MHCC97L cells as control to screen a group of HCC metastasis- and cell-specific DNA aptamers. One of selected aptamers, LY-1, could specifically bind to metastatic HCC with a dissociation constant (Kd) in nanomolar range. In vitro studies demonstrated that LY-1 can recognize and bind to membrane protein of metastatic HCC cells. Furthermore, QD605 labeled LY-1 aptamer could recognize HCC cells in both local liver cancer tissues and pulmonary metastatic sites in a xenograft model of HCC with pulmonary metastasis. Further biochemical and immunostaining studies showed that LY-1 could selectively bind to a subpopulation of more metastatic cells in HCCLM9 cells, which express more CK19 and vimentin. Finally, treatment of highly metastatic cells with LY-1 led to reduced migration and invasiveness of HCCLM9 cells in vitro and suppression of xenograft growth in vivo. Taken together, the present study demonstrated the tumor targeting and tumor suppressive effects of LY-1, which could be a promising molecular probe for metastatic HCC and a potential candidate of chemotherapy for metastatic HCC.

  5. Identification of unique expression signatures and therapeutic targets in esophageal squamous cell carcinoma

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    Yan Wusheng

    2012-01-01

    Full Text Available Abstract Background Esophageal squamous cell carcinoma (ESCC, the predominant histological subtype of esophageal cancer, is characterized by high mortality. Previous work identified important mRNA expression differences between normal and tumor cells; however, to date there are limited ex vivo studies examining expression changes occurring during normal esophageal squamous cell differentiation versus those associated with tumorigenesis. In this study, we used a unique tissue microdissection strategy and microarrays to measure gene expression profiles associated with cell differentiation versus tumorigenesis in twelve cases of patient-matched normal basal squamous epithelial cells (NB, normal differentiated squamous epithelium (ND, and squamous cell cancer. Class comparison and pathway analysis were used to compare NB versus tumor in a search for unique therapeutic targets. Results As a first step towards this goal, gene expression profiles and pathways were evaluated. Overall, ND expression patterns were markedly different from NB and tumor; whereas, tumor and NB were more closely related. Tumor showed a general decrease in differentially expressed genes relative to NB as opposed to ND that exhibited the opposite trend. FSH and IgG networks were most highly dysregulated in normal differentiation and tumorigenesis, respectively. DNA repair pathways were generally elevated in NB and tumor relative to ND indicating involvement in both normal and pathological growth. PDGF signaling pathway and 12 individual genes unique to the tumor/NB comparison were identified as therapeutic targets, and 10 associated ESCC gene-drug pairs were identified. We further examined the protein expression level and the distribution patterns of four genes: ODC1, POSTN, ASPA and IGF2BP3. Ultimately, three genes (ODC1, POSTN, ASPA were verified to be dysregulated in the same pattern at both the mRNA and protein levels. Conclusions These data reveal insight into genes and

  6. Identification, characterization and target gene analysis of testicular microRNAs in the oriental fruit fly Bactrocera dorsalis.

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    Tariq, K; Peng, W; Saccone, G; Zhang, H

    2016-02-01

    MicroRNAs (miRNAs) are small noncoding RNAs that regulate various diverse biological processes including insect spermatogenesis. The oriental fruit fly, Bactrocera dorsalis, is one of the most destructive horticultural pests in East Asia and the Pacific region. Although developmental miRNA profiles of B. dorsalis have enriched our knowledge, specific testicular miRNAs in this dipteran species are unexplored. In this study, we identified miRNAs from B. dorsalis testes by deep sequencing, which provided an overview of miRNA expression during spermatogenesis. Small RNA libraries were constructed from the testes of fully mature (FM), immature (IM) and middle-aged (MA) adult flies of B. dorsalis. Small RNA sequencing and data analysis revealed 172 known and 78 novel miRNAs amongst these libraries. Pairwise comparisons of libraries led to the identification of 24, 15 and 14 differentially expressed miRNAs in FM vs. IM, FM vs. MA and IM vs. MA insects, respectively. Using a bioinformatic approach, we predicted 124 target genes against the 13 most differentially expressed miRNAs. Furthermore, the expression patterns of six randomly selected miRNAs (from the 13 most differentially expressed miRNAs) and their putative target genes (from the 124 predicted target genes) were analysed in the testis of B. dorsalis by quantitative real-time PCR, which showed that out of six, four tested miRNAs-mRNAs had an inverse expression pattern and are probably co-regulated. This study is the first comparative profile of the miRNA transcriptome in three developmental stages of the testis, and provides a useful resource for further studies on the role of miRNAs in spermatogenesis in B. dorsalis. © 2015 The Royal Entomological Society.

  7. Identification of drought-responsive microRNAs and their targets in Ammopiptanthus mongolicus by using high-throughput sequencing

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    Gao, Fei; Wang, Ning; Li, Huayun; Liu, Jisheng; Fu, Chenxi; Xiao, Zihua; Wei, Chunxiang; Lu, Xiaoduo; Feng, Jinchao; Zhou, Yijun

    2016-01-01

    MicroRNAs (miRNAs) regulate target gene expression to modulate plant growth, development, and biotic and abiotic stress response at the post-transcriptional level. Ammopiptanthus mongolicus, an ecologically important desert plant, is increasingly used as a model for studying stress tolerance in plants. The miRNA-mediated gene regulatory network might remarkably contribute to the high stress tolerance of A. mongolicus. However, a genome-wide identification of miRNAs and their targets is still lacking in A. mongolicus. In this study, 170 conserved and 156 non-conserved miRNAs were identified in A. mongolicus. We experimentally identified 298 miRNA-target pairs from the degradome data. Quantitative real-time polymerase chain reaction analyses identified 28 drought-responsive miRNAs in leaves and 15 in roots. Some characteristics of the miRNA-mediated regulatory network were found in A. mongolicus. Multiple miRNAs, including 2 newly identified non-conserved miRNAs, miR-P11 and miR-P14, generated from the precursors of miR169, were found to be involved in drought stress response. Further, miR2118 and miR858 participated in drought stress response by up-regulating OZF1 gene and certain MYB genes that were involved in the regulation of flavonol biosynthesis in A. mongolicus. The findings of this study might provide new insights for understanding the functions of miRNA in stress response in plants. PMID:27698373

  8. An improved DS acoustic-seismic modality fusion algorithm based on a new cascaded fuzzy classifier for ground-moving targets classification in wireless sensor networks

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    Pan, Qiang; Wei, Jianming; Cao, Hongbing; Li, Na; Liu, Haitao

    2007-04-01

    A new cascaded fuzzy classifier (CFC) is proposed to implement ground-moving targets classification tasks locally at sensor nodes in wireless sensor networks (WSN). The CFC is composed of three and two binary fuzzy classifiers (BFC) respectively in seismic and acoustic signal channel in order to classify person, Light-wheeled (LW) Vehicle, and Heavywheeled (HW) Vehicle in presence of environmental background noise. Base on the CFC, a new basic belief assignment (bba) function is defined for each component BFC to give out a piece of evidence instead of a hard decision label. An evidence generator is used to synthesize available evidences from BFCs into channel evidences and channel evidences are further temporal-fused. Finally, acoustic-seismic modality fusion using Dempster-Shafer method is performed. Our implementation gives significantly better performance than the implementation with majority-voting fusion method through leave-one-out experiments.

  9. Identification of putative TAL effector targets of the citrus canker pathogens shows functional convergence underlying disease development and defense response.

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    Pereira, Andre L A; Carazzolle, Marcelo F; Abe, Valeria Y; de Oliveira, Maria L P; Domingues, Mariane N; Silva, Jaqueline C; Cernadas, Raul A; Benedetti, Celso E

    2014-02-25

    Transcriptional activator-like (TAL) effectors, formerly known as the AvrBs3/PthA protein family, are DNA-binding effectors broadly found in Xanthomonas spp. that transactivate host genes upon injection via the bacterial type three-secretion system. Biologically relevant targets of TAL effectors, i.e. host genes whose induction is vital to establish a compatible interaction, have been reported for xanthomonads that colonize rice and pepper; however, citrus genes modulated by the TAL effectors PthA"s" and PthC"s" of the citrus canker bacteria Xanthomonas citri (Xc) and Xanthomonas aurantifolii pathotype C (XaC), respectively, are poorly characterized. Of particular interest, XaC causes canker disease in its host lemon (Citrus aurantifolia), but triggers a defense response in sweet orange. Based on, 1) the TAL effector-DNA binding code, 2) gene expression data of Xc and XaC-infiltrated sweet orange leaves, and 3) citrus hypocotyls transformed with PthA2, PthA4 or PthC1, we have identified a collection of Citrus sinensis genes potentially targeted by Xc and XaC TAL effectors. Our results suggest that similar with other strains of Xanthomonas TAL effectors, PthA2 and PthA4, and PthC1 to some extent, functionally converge. In particular, towards induction of genes involved in the auxin and gibberellin synthesis and response, cell division, and defense response. We also present evidence indicating that the TAL effectors act as transcriptional repressors and that the best scoring predicted DNA targets of PthA"s" and PthC"s" in citrus promoters predominantly overlap with or localize near to TATA boxes of core promoters, supporting the idea that TAL effectors interact with the host basal transcriptional machinery to recruit the RNA pol II and start transcription. The identification of PthA"s" and PthC"s" targets, such as the LOB (lateral organ boundary) and CCNBS genes that we report here, is key for the understanding of the canker symptoms development during host

  10. De-novo identification of PPARgamma/RXR binding sites and direct targets during adipogenesis.

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    Mohamed Sabry Hamza

    Full Text Available BACKGROUND: The pathophysiology of obesity and type 2 diabetes mellitus is associated with abnormalities in endocrine signaling in adipose tissue and one of the key signaling affectors operative in these disorders is the nuclear hormone transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma. PPARgamma has pleiotropic functions affecting a wide range of fundamental biological processes including the regulation of genes that modulate insulin sensitivity, adipocyte differentiation, inflammation and atherosclerosis. To date, only a limited number of direct targets for PPARgamma have been identified through research using the well established pre-adipogenic cell line, 3T3-L1. In order to obtain a genome-wide view of PPARgamma binding sites, we applied the pair end-tagging technology (ChIP-PET to map PPARgamma binding sites in 3T3-L1 preadipocyte cells. METHODOLOGY/PRINCIPAL FINDINGS: Coupling gene expression profile analysis with ChIP-PET, we identified in a genome-wide manner over 7700 DNA binding sites of the transcription factor PPARgamma and its heterodimeric partner RXR during the course of adipocyte differentiation. Our validation studies prove that the identified sites are bona fide binding sites for both PPARgamma and RXR and that they are functionally capable of driving PPARgamma specific transcription. Our results strongly indicate that PPARgamma is the predominant heterodimerization partner for RXR during late stages of adipocyte differentiation. Additionally, we find that PPARgamma/RXR association is enriched within the proximity of the 5' region of the transcription start site and this association is significantly associated with transcriptional up-regulation of genes involved in fatty acid and lipid metabolism confirming the role of PPARgamma as the master transcriptional regulator of adipogenesis. Evolutionary conservation analysis of these binding sites is greater when adjacent to up-regulated genes than down

  11. Ground-based characterization of Leucus and Polymele, two fly-by targets of the Lucy Discovery mission

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    Buie, Marc W.; Zangari, Amanda Marie; Marchi, Simone; Mottola, Stefano; Levison, Harold F.

    2016-10-01

    Lucy is a proposed NASA Discovery mission designed to perform close fly-bys with six Jupiter Trojan asteroids. The mission, which is currently in the Phase A development phase, is planned to launch in 2021 and arrive at the L4 Trojan cloud in 2027. We report on the results of an observational campaign of (11351) Leucus and (15094) Polymele conducted this year. The goal is to characterize their shape, spin state and photometric properties to aid in mission planning and to complement the mission data. Leucus was previously observed by French et al (2013) where they reported a 514 hour rotation period with a lightcurve amplitude as high as 1 magnitude. Our data confirm a long-period and high-amplitude lightcurve but with a period closer to 440 hours. The lightcurve shape has a symmetric double-peaked shape with a ~0.7mag peak-to-peak amplitude. Initial results for Polymele indicate a low-amplitude lightcurve at or below 0.1 mag with a period near 4 hours. Thus, the Lucy target sample includes bodies with among the slowest and fastest rotation rates. Additional observations will be required to further refine the period and pole orientation for both bodies. This year's data are especially challenging due to observing at low galactic latitude. We will report on final results of this year's campaign along with our methods for removing field confusion using optimal image subtraction and photometric calibration based on the new APASS catalog (Henden et al, 2012).

  12. Metabolomics as a tool for target identification in strain improvement: the influence of phenotype definition.

    Science.gov (United States)

    Braaksma, Machtelt; Bijlsma, Sabina; Coulier, Leon; Punt, Peter J; van der Werf, Mariët J

    2011-01-01

    For the optimization of microbial production processes, the choice of the quantitative phenotype to be optimized is crucial. For instance, for the optimization of product formation, either product concentration or productivity can be pursued, potentially resulting in different targets for strain improvement. The choice of a quantitative phenotype is highly relevant for classical improvement approaches, and even more so for modern systems biology approaches. In this study, the information content of a metabolomics dataset was determined with respect to different quantitative phenotypes related to the formation of specific products. To this end, the production of two industrially relevant products by Aspergillus niger was evaluated: (i) the enzyme glucoamylase, and (ii) the more complex product group of secreted proteases, consisting of multiple enzymes. For both products, six quantitative phenotypes associated with activity and productivity were defined, also taking into account different time points of sampling during the fermentation. Both linear and nonlinear relationships between the metabolome data and the different quantitative phenotypes were considered. The multivariate data analysis tool partial least-squares (PLS) was used to evaluate the information content of the datasets for all the different quantitative phenotypes defined. Depending on the product studied, different quantitative phenotypes were found to have the highest information content in specific metabolomics datasets. A detailed analysis of the metabolites that showed strong correlation with these quantitative phenotypes revealed that various sugar derivatives correlated with glucoamylase activity. For the reduction of protease activity, mainly as-yet-unidentified compounds correlated.

  13. Identification of ligands that target the HCV-E2 binding site on CD81

    Science.gov (United States)

    Olaby, Reem Al; Azzazy, Hassan M.; Harris, Rodney; Chromy, Brett; Vielmetter, Jost; Balhorn, Rod

    2013-04-01

    Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.

  14. Computer-assisted identification of novel small molecule inhibitors targeting GLUT1

    Science.gov (United States)

    Wan, Zhining; Li, Xin; Sun, Rong; Li, Yuanyuan; Wang, Xiaoyun; Li, Xinru; Rong, Li; Shi, Zheng; Bao, Jinku

    2015-12-01

    Glucose transporters (GLUTs) are the main carriers of glucose that facilitate the diffusion of glucose in mammalian cells, especially GLUT1. Notably, GLUT1 is a rate-limiting transporter for glucose uptake, and its overexpression is a common characteristic in most cancers. Thus, the inhibition of GLUT1 by novel small compounds to lower glucose levels for cancer cells has become an emerging strategy. Herein, we employed high-throughput screening approaches to identify potential inhibitors against the sugar-binding site of GLUT1. Firstly, molecular docking screening was launched against the specs products, and three molecules (ZINC19909927, ZINC19908826, and ZINC19815451) were selected as candidate GLUT1 inhibitors for further analysis. Then, taking the initial ligand β-NG as a reference, molecular dynamic (MD) simulations and molecular mechanics/generalized born surface area (MM/GBSA) method were applied to evaluate the binding stability and affinity of the three candidates towards GLUT1. Finally, we found that ZINC19909927 might have the highest affinity to occupy the binding site of GLUT1. Meanwhile, energy decomposition analysis identified several residues located in substrate-binding site that might provide clues for future inhibitor discovery towards GLUT1. Taken together, these results in our study may provide valuable information for identifying new inhibitors targeting GLUT1-mediated glucose transport and metabolism for cancer therapeutics.

  15. Identification of a New Peptide for Fibrosarcoma Tumor Targeting and Imaging In Vivo

    Directory of Open Access Journals (Sweden)

    Chia-Che Wu

    2010-01-01

    Full Text Available A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of 131I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data suggest that TK4 holds promise as a lead structure for tumor targeting, and it could be further applied in the development of diagnostic or therapeutic agent.

  16. Identification of a new peptide for fibrosarcoma tumor targeting and imaging in vivo.

    Science.gov (United States)

    Wu, Chia-Che; Lin, Erh-Hsuan; Lee, Yu-Ching; Tai, Cheng-Jeng; Kuo, Tsu-Hsiang; Wang, Hsin-Ell; Luo, Tsai-Yueh; Fu, Ying-Kai; Chen, Haw-Jan; Sun, Ming-Ding; Wu, Chih-Hsiung; Wu, Cheng-Wen; Leu, Sy-Jye; Deng, Win-Ping

    2010-01-01

    A 12-mer amino acid peptide SATTHYRLQAAN, denominated TK4, was isolated from a phage-display library with fibrosarcoma tumor-binding activity. In vivo biodistribution analysis of TK4-displaying phage showed a significant increased phage titer in implanted tumor up to 10-fold in comparison with normal tissues after systemic administration in mouse. Competition assay confirmed that the binding of TK4-phage to tumor cells depends on the TK4 peptide. Intravenous injection of (131)I-labeled synthetic TK4 peptide in mice showed a tumor retention of 3.3% and 2.7% ID/g at 1- and 4-hour postinjection, respectively. Tumor-to-muscle ratio was 1.1, 5.7, and 3.2 at 1-, 4-, and 24-hour, respectively, and tumors were imaged on a digital γ-camera at 4-hour postinjection. The present data suggest that TK4 holds promise as a lead structure for tumor targeting, and it could be further applied in the development of diagnostic or therapeutic agent.

  17. Identification of novel human WW domain-containing proteins by cloning of ligand targets.

    Science.gov (United States)

    Pirozzi, G; McConnell, S J; Uveges, A J; Carter, J M; Sparks, A B; Kay, B K; Fowlkes, D M

    1997-06-06

    A recently described protein module consisting of 35-40 semiconserved residues, termed the WW domain, has been identified in a number of diverse proteins including dystrophin and Yes-associated protein (YAP). Two putative ligands of YAP, termed WBP-1 and WBP-2, have been found previously to contain several short peptide regions consisting of PPPPY residues (PY motif) that mediate binding to the WW domain of YAP. Although the function(s) of the WW domain remain to be elucidated, these observations strongly support a role for the WW domain in protein-protein interactions. Here we report the isolation of three novel human cDNAs encoding a total of nine WW domains, using a newly developed approach termed COLT (cloning of ligand targets), in which the rapid cloning of modular protein domains is accomplished by screening cDNA expression libraries with specific peptide ligands. Two of the new genes identified appear to be members of a family of proteins, including Rsp5 and Nedd-4, which have ubiquitin-protein ligase activity. In addition, we demonstrate that peptides corresponding to PY and PY-like motifs present in several known signaling or regulatory proteins, including RasGAP, AP-2, p53BP-2 (p53-binding protein-2), interleukin-6 receptor-alpha, chloride channel CLCN5, and epithelial sodium channel ENaC, can selectively bind to certain of these novel WW domains.

  18. Transcription Factors Expressed in Lateral Organ Boundaries: Identification of Downstream Targets

    Energy Technology Data Exchange (ETDEWEB)

    Springer, Patricia S

    2010-07-12

    The processes of lateral organ initiation and patterning are central to the generation of mature plant form. Characterization of the molecular mechanisms underlying these processes is essential to our understanding of plant development. Communication between the shoot apical meristem and initiating organ primordia is important both for functioning of the meristem and for proper organ patterning, and very little is known about this process. In particular, the boundary between meristem and leaf is emerging as a critical region that is important for SAM maintenance and regulation of organogenesis. The goal of this project was to characterize three boundary-expressed genes that encode predicted transcription factors. Specifically, we have studied LATERAL ORGAN BOUNDARIES (LOB), LATERAL ORGAN FUSION1 (LOF1), and LATERAL ORGAN FUSION2 (LOF2). LOB encodes the founding member of the LOB-DOMAIN (LBD) plant-specific DNA binding transcription factor family and LOF1 and LOF2 encode paralogous MYB-domain transcription factors. We characterized the genetic relationship between these three genes and other boundary and meristem genes. We also used an ectopic inducible expression system to identify direct targets of LOB.

  19. Identification of dopaminergic neurons of the substantia nigra pars compacta as a target of manganese accumulation

    Science.gov (United States)

    Robison, Gregory; Sullivan, Brendan; Cannon, Jason R.; Pushkar, Yulia

    2015-01-01

    Manganese serves as a cofactor to a variety of proteins necessary for proper bodily development and function. However, an overabundance of Mn in the brain can result in manganism, a neurological condition resembling Parkinson’s disease (PD). Bulk sample measurement techniques have identified the globus pallidus and thalamus as targets of Mn accumulation in the brain, however smaller structures/cells cannot be measured. Here, X-ray fluorescence microscopy determined the metal content and distribution in the substantia nigra (SN) of the rodent brain. In vivo retrograde labeling of dopaminergic cells (via FluoroGold™) of the SN pars compacta (SNc) subsequently allowed for XRF imaging of dopaminergic cells in situ at subcellular resolution. Chronic Mn exposure resulted in a significant Mn increase in both the SN pars reticulata (>163%) and the SNc (>170%) as compared to control; no other metal concentrations were significantly changed. Subcellular imaging of dopaminergic cells demonstrated that Mn is located adjacent to the nucleus. Measured intracellular manganese concentrations range between 40–200 μM; concentrations as low as 100 μM have been observed to cause cell death in cell cultures. Direct observation of Mn accumulation in the SNc could establish a biological basis for movement disorders associated with manganism, specifically Mn caused insult to the SNc. Accumulation of Mn in dopaminergic cells of the SNc may help clarify the relationship between Mn and the loss of motor skills associated with manganism. PMID:25695229

  20. Construction and identification of Fas-targeting siRNA-expressing plasmid

    Institute of Scientific and Technical Information of China (English)

    LIU Su-hu; ZHANG Wang-gang; ZHANG Mei; ZHU Qing; TIAN Wei

    2005-01-01

    Objective: To study the therapeutic potential of Fas inhibition in different diseases, a Fas-targeting siRNA (small interfering)-expressing plasmid was constructed. Methods: The U6 promoter cassette and siFas (small interfering RNA that inhibit Fas expression) template sequence were obtained by PCR method. They were cloned into modified pcDNA3.1. The resultant plasmid pU6-siFas was transfected into P815 cells with lipofectin2000 and selected under G-418-containing culture medium. Fas inhibition in stably transfected cells was detected by immunocytochemistry. Results: The plasmid pU6-siFas efficiently reduced the expression of Fas and conferred G-418 resistance in P815 cells. Conclusion: The successful construction of the siRNA expressing plasmid will facilitate the application of RNA interference technique and lay the foundation for further study of Fas inhibition in the treatment of different diseases such as aplastic anemia and acute liver failure.

  1. Identification of novel knockout targets for improving terpenoids biosynthesis in Saccharomyces cerevisiae.

    Science.gov (United States)

    Sun, Zhiqiang; Meng, Hailin; Li, Jing; Wang, Jianfeng; Li, Qian; Wang, Yong; Zhang, Yansheng

    2014-01-01

    Many terpenoids have important pharmacological activity and commercial value; however, application of these terpenoids is often limited by problems associated with the production of sufficient amounts of these molecules. The use of Saccharomyces cerevisiae (S. cerevisiae) for the production of heterologous terpenoids has achieved some success. The objective of this study was to identify S. cerevisiae knockout targets for improving the synthesis of heterologous terpeniods. On the basis of computational analysis of the S. cerevisiae metabolic network, we identified the knockout sites with the potential to promote terpenoid production and the corresponding single mutant was constructed by molecular manipulations. The growth rates of these strains were measured and the results indicated that the gene deletion had no adverse effects. Using the expression of amorphadiene biosynthesis as a testing model, the gene deletion was assessed for its effect on the production of exogenous terpenoids. The results showed that the dysfunction of most genes led to increased production of amorphadiene. The yield of amorphadiene produced by most single mutants was 8-10-fold greater compared to the wild type, indicating that the knockout sites can be engineered to promote the synthesis of exogenous terpenoids.

  2. Challenges and strategies for targeted phosphorylation site identification and quantification using mass spectrometry analysis.

    Science.gov (United States)

    Blackburn, Kevin; Goshe, Michael B

    2009-03-01

    Despite its importance, the 'ultimate' method to identify and quantify site-specific protein phosphorylation using mass spectrometry (MS) has yet to be established. This is as much a function of the dynamic range of instrumentation as it is the complexities surrounding the isolation and behavior of phosphopeptides. Phosphorylation site analysis using MS can be quite challenging when analyzing just one protein and quickly becomes a daunting task when attempting to perform proteome-wide measurements. Data-dependent tandem MS-based methods which are useful for the discovery and characterization of novel phosphorylation sites often lack the dynamic range and quantitative aspect required for studying the temporal phases of phosphorylation. While targeted methods such as multiple reaction monitoring do provide a highly specific and quantitative methodology for studying phosphorylation changes over time, they are not suited for initial discovery of previously unreported sites of phosphorylation. Data-independent acquisition represents a relatively new approach for simultaneous qualitative and quantitative sample analysis which holds promise for filling this technological gap.

  3. Identification of Goodpasture target antigens in basement membranes of human glomeruli, lung, and placenta.

    Science.gov (United States)

    Weber, M; Köhler, H; Manns, M; Baum, H P; Meyer zum Büschenfelde, K H

    1987-01-01

    Collagenase-digests of human glomerular (GBM), alveolar (ABM), and placenta basement membranes (PBM) were separated by gel filtration columns and the pools rich in Goodpasture antigens (GP) were identified by an antibody inhibition-ELISA. Sodium dodecyl sulphate-polyacrylamide gel electrophoresis (SDS-PAGE) followed by immunoblotting on nitrocellulose membranes was performed with each basement membrane preparation. Sera from patients with florid GP-syndrome and antibodies to glomerular basement membrane (anti-GBM antibodies) were incubated with nitrocellulose strips of GBM, ABM, and PBM. Immunoperoxidase staining revealed reactivity with target antigens of 24, 26, 44, and 50 kD in the GBM and of 44 and 50 kD in the ABM and PBM, respectively. No corresponding reactivity was observed using convalescent GP-sera, sera from patients with other immunological diseases or sera from healthy blood donors. The antigens were sensitive to reduction. We conclude, that antigens of similar molecular-weights can be identified by anti-GBM positive sera in human glomerular, alveolar and placenta basement membranes. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:3608225

  4. Identification of ligands that target the HCV-E2 binding site on CD81.

    Science.gov (United States)

    Olaby, Reem Al; Azzazy, Hassan M; Harris, Rodney; Chromy, Brett; Vielmetter, Jost; Balhorn, Rod

    2013-04-01

    Hepatitis C is a global health problem. While many drug companies have active R&D efforts to develop new drugs for treating Hepatitis C virus (HCV), most target the viral enzymes. The HCV glycoprotein E2 has been shown to play an essential role in hepatocyte invasion by binding to CD81 and other cell surface receptors. This paper describes the use of AutoDock to identify ligand binding sites on the large extracellular loop of the open conformation of CD81 and to perform virtual screening runs to identify sets of small molecule ligands predicted to bind to two of these sites. The best sites selected by AutoLigand were located in regions identified by mutational studies to be the site of E2 binding. Thirty-six ligands predicted by AutoDock to bind to these sites were subsequently tested experimentally to determine if they bound to CD81-LEL. Binding assays conducted using surface Plasmon resonance revealed that 26 out of 36 (72 %) of the ligands bound in vitro to the recombinant CD81-LEL protein. Competition experiments performed using dual polarization interferometry showed that one of the ligands predicted to bind to the large cleft between the C and D helices was also effective in blocking E2 binding to CD81-LEL.

  5. Computational identification of microRNAs and their targets in cassava (Manihot esculenta Crantz.).

    Science.gov (United States)

    Patanun, Onsaya; Lertpanyasampatha, Manassawe; Sojikul, Punchapat; Viboonjun, Unchera; Narangajavana, Jarunya

    2013-03-01

    MicroRNAs (miRNAs) are a newly discovered class of noncoding endogenous small RNAs involved in plant growth and development as well as response to environmental stresses. miRNAs have been extensively studied in various plant species, however, only few information are available in cassava, which serves as one of the staple food crops, a biofuel crop, animal feed and industrial raw materials. In this study, the 169 potential cassava miRNAs belonging to 34 miRNA families were identified by computational approach. Interestingly, mes-miR319b was represented as the first putative mirtron demonstrated in cassava. A total of 15 miRNA clusters involving 7 miRNA families, and 12 pairs of sense and antisense strand cassava miRNAs belonging to six different miRNA families were discovered. Prediction of potential miRNA target genes revealed their functions involved in various important plant biological processes. The cis-regulatory elements relevant to drought stress and plant hormone response were identified in the promoter regions of those miRNA genes. The results provided a foundation for further investigation of the functional role of known transcription factors in the regulation of cassava miRNAs. The better understandings of the complexity of miRNA-mediated genes network in cassava would unravel cassava complex biology in storage root development and in coping with environmental stresses, thus providing more insights for future exploitation in cassava improvement.

  6. Identification of active release planes using ground-based differential InSAR at the Randa rock slope instability, Switzerland

    Directory of Open Access Journals (Sweden)

    V. Gischig

    2009-12-01

    Full Text Available Five ground-based differential interferometric synthetic aperture radar (GB-DInSAR surveys were conducted between 2005 and 2007 at the rock slope instability at Randa, Switzerland. Resultant displacement maps revealed, for the first time, the presence of an active basal rupture zone and a lateral release surface daylighting on the exposed 1991 failure scarp. Structures correlated with the boundaries of interferometric displacement domains were confirmed using a helicopter-based LiDAR DTM and oblique aerial photography. Former investigations at the site failed to conclusively detect these active release surfaces essential for kinematic and hazard analysis of the instability, although their existence had been hypothesized. The determination of the basal and lateral release planes also allowed a more accurate estimate of the currently unstable volume of 5.7±1.5 million m3. The displacement patterns reveal that two different kinematic behaviors dominate the instability, i.e. toppling above 2200 m and translational failure below. In the toppling part of the instability the areas with the highest GB-DInSAR displacements correspond to areas of enhanced micro-seismic activity. The observation of only few strongly active discontinuities daylighting on the 1991 failure surface points to a rather uniform movement in the lower portion of the instability, while most of the slip occurs along the basal rupture plane. Comparison of GB-DInSAR displacements with mapped discontinuities revealed correlations between displacement patterns and active structures, although spatial offsets occur as a result of the effective resolution of GB-DInSAR. Similarly, comparisons with measurements from total station surveys generally showed good agreement. Discrepancies arose in several cases due to local movement of blocks, the size of which could not be resolved using GB-DInSAR.

  7. Identification of potential target genes associated with the pathogenesis of osteoarthritis using microarray based analysis.

    Science.gov (United States)

    Li, Meng; Zhi, Liqiang; Zhang, Zhi; Bian, Weiguo; Qiu, Yusheng

    2017-09-01

    The aim of the present study was to investigate the molecular circuitry of osteoarthritis (OA) and identify more potential target genes for OA treatment. Microarray data of GSE32317 was downloaded from the National Center for Biotechnology Information Gene Expression Omnibus database. Differentially expressed genes (DEGs) were identified in samples of synovial membrane from patients with early stage of knee OA (OA_Early) and late stage of knee OA (OA_End) that were compared with healthy specimens. Bioinformatics analysis was applied to analyze the significant functions and pathways that were enriched by the common DEGs identified in OA_Early and OA_End samples. Furthermore, a protein‑protein interaction (PPI) network was constructed and significant modules were extracted. Transcription factors (TFs) that could regulate genes in the significant modules were identified. A total of 1,207 and 1,575 DEGs were identified in OA_Early and OA_End samples compared with healthy samples, respectively. A total of 740 genes were upregulated and 308 genes were downregulated across the OA_Early and OA_End samples. These common DEGs were enriched in different gene ontology terms and pathways, such as immune response. Angiotensinogen (AGT) and C‑X‑C motif chemokine ligand 12 (CXCL12) were identified to be hub proteins in the PPI network or in the selected module 1. In addition, the DEG lysine demethylase 2B (KDM2B) was identified as a TF that can regulate genes in the significant modules 2 and 3. In conclusion, the present study has identified AGT, CXCL12 and KDM2B as potentially essential genes associated with the pathogenesis of knee OA.

  8. Identification of Rorβ targets in cultured osteoblasts and in human bone

    Energy Technology Data Exchange (ETDEWEB)

    Roforth, Matthew M., E-mail: roforth.matthew@mayo.edu; Khosla, Sundeep, E-mail: khosla.sundeep@mayo.edu; Monroe, David G., E-mail: monroe.david@mayo.edu

    2013-11-01

    Highlights: •We examine the gene expression patterns controlled by Rorβ in osteoblasts. •Genes involved in extracellular matrix regulation and proliferation are affected. •Rorβ mRNA levels increase in aged, human bone biopsies. •Rorβ may affect osteoblast activity by modulation of these pathways. -- Abstract: Control of osteoblastic bone formation involves the cumulative action of numerous transcription factors, including both activating and repressive functions that are important during specific stages of differentiation. The nuclear receptor retinoic acid receptor-related orphan receptor β (Rorβ) has been recently shown to suppress the osteogenic phenotype in cultured osteoblasts, and is highly upregulated in bone marrow-derived osteogenic precursors isolated from aged osteoporotic mice, suggesting Rorβ is an important regulator of osteoblast function. However the specific gene expression patterns elicited by Rorβ are unknown. Using microarray analysis, we identified 281 genes regulated by Rorβ in an MC3T3-E1 mouse osteoblast cell model (MC3T3-Rorβ-GFP). Pathway analysis revealed alterations in genes involved in MAPK signaling, genes involved in extracellular matrix (ECM) regulation, and cytokine-receptor interactions. Whereas the identified Rorβ-regulated ECM genes normally decline during osteoblastic differentiation, they were highly upregulated in this non-mineralizing MC3T3-Rorβ-GFP model system, suggesting that Rorβ may exert its anti-osteogenic effects through ECM disruption. Consistent with these in vitro findings, the expression of both RORβ and a subset of RORβ-regulated genes were increased in bone biopsies from postmenopausal women (73 ± 7 years old) compared to premenopausal women (30 ± 5 years old), suggesting a role for RORβ in human age-related bone loss. Collectively, these data demonstrate that Rorβ regulates known osteogenic pathways, and may represent a novel therapeutic target for age-associated bone loss.

  9. Identification of the DEAD box RNA helicase DDX3 as a therapeutic target in colorectal cancer.

    Science.gov (United States)

    Heerma van Voss, Marise R; Vesuna, Farhad; Trumpi, Kari; Brilliant, Justin; Berlinicke, Cynthia; de Leng, Wendy; Kranenburg, Onno; Offerhaus, G Johan; Bürger, Horst; van der Wall, Elsken; van Diest, Paul J; Raman, Venu

    2015-09-29

    Identifying druggable targets in the Wnt-signaling pathway can optimize colorectal cancer treatment. Recent studies have identified a member of the RNA helicase family DDX3 (DDX3X) as a multilevel activator of Wnt signaling in cells without activating mutations in the Wnt-signaling pathway. In this study, we evaluated whether DDX3 plays a role in the constitutively active Wnt pathway that drives colorectal cancer. We determined DDX3 expression levels in 303 colorectal cancers by immunohistochemistry. 39% of tumors overexpressed DDX3. High cytoplasmic DDX3 expression correlated with nuclear β-catenin expression, a marker of activated Wnt signaling. Functionally, we validated this finding in vitro and found that inhibition of DDX3 with siRNA resulted in reduced TCF4-reporter activity and lowered the mRNA expression levels of downstream TCF4-regulated genes. In addition, DDX3 knockdown in colorectal cancer cell lines reduced proliferation and caused a G1 arrest, supporting a potential oncogenic role of DDX3 in colorectal cancer. RK-33 is a small molecule inhibitor designed to bind to the ATP-binding site of DDX3. Treatment of colorectal cancer cell lines and patient-derived 3D cultures with RK-33 inhibited growth and promoted cell death with IC50 values ranging from 2.5 to 8 μM. The highest RK-33 sensitivity was observed in tumors with wild-type APC-status and a mutation in CTNNB1. Based on these results, we conclude that DDX3 has an oncogenic role in colorectal cancer. Inhibition of DDX3 with the small molecule inhibitor RK-33 causes inhibition of Wnt signaling and may therefore be a promising future treatment strategy for a subset of colorectal cancers.

  10. Identification and Validation of Small-Gatekeeper Kinases as Drug Targets in Giardia lamblia.

    Science.gov (United States)

    Hennessey, Kelly M; Smith, Tess R; Xu, Jennifer W; Alas, Germain C M; Ojo, Kayode K; Merritt, Ethan A; Paredez, Alexander R

    2016-11-01

    Giardiasis is widely acknowledged to be a neglected disease in need of new therapeutics to address toxicity and resistance issues associated with the limited available treatment options. We examined seven protein kinases in the Giardia lamblia genome that are predicted to share an unusual structural feature in their active site. This feature, an expanded active site pocket resulting from an atypically small gatekeeper residue, confers sensitivity to "bumped" kinase inhibitors (BKIs), a class of compounds that has previously shown good pharmacological properties and minimal toxicity. An initial phenotypic screen for biological activity using a subset of an in-house BKI library found that 5 of the 36 compounds tested reduced trophozoite growth by at least 50% at a concentration of 5 μM. The cellular localization and the relative expression levels of the seven protein kinases of interest were determined after endogenously tagging the kinases. Essentiality of these kinases for parasite growth and infectivity were evaluated genetically using morpholino knockdown of protein expression to establish those that could be attractive targets for drug design. Two of the kinases were critical for trophozoite growth and attachment. Therefore, recombinant enzymes were expressed, purified and screened against a BKI library of >400 compounds in thermal stability assays in order to identify high affinity compounds. Compounds with substantial thermal stabilization effects on recombinant protein were shown to have good inhibition of cell growth in wild-type G. lamblia and metronidazole-resistant strains of G. lamblia. Our data suggest that BKIs are a promising starting point for the development of new anti-giardiasis therapeutics that do not overlap in mechanism with current drugs.

  11. Identification of Small Molecule Inhibitors of Human Cytochrome c Oxidase That Target Chemoresistant Glioma Cells.

    Science.gov (United States)

    Oliva, Claudia R; Markert, Tahireh; Ross, Larry J; White, E Lucile; Rasmussen, Lynn; Zhang, Wei; Everts, Maaike; Moellering, Douglas R; Bailey, Shannon M; Suto, Mark J; Griguer, Corinne E

    2016-11-11

    The enzyme cytochrome c oxidase (CcO) or complex IV (EC 1.9.3.1) is a large transmembrane protein complex that serves as the last enzyme in the respiratory electron transport chain of eukaryotic mitochondria. CcO promotes the switch from glycolytic to oxidative phosphorylation (OXPHOS) metabolism and has been associated with increased self-renewal characteristics in gliomas. Increased CcO activity in tumors has been associated with tumor progression after chemotherapy failure, and patients with primary glioblastoma multiforme and high tumor CcO activity have worse clinical outcomes than those with low tumor CcO activity. Therefore, CcO is an attractive target for cancer therapy. We report here the characterization of a CcO inhibitor (ADDA 5) that was identified using a high throughput screening paradigm. ADDA 5 demonstrated specificity for CcO, with no inhibition of other mitochondrial complexes or other relevant enzymes, and biochemical characterization showed that this compound is a non-competitive inhibitor of cytochrome c When tested in cellular assays, ADDA 5 dose-dependently inhibited the proliferation of chemosensitive and chemoresistant glioma cells but did not display toxicity against non-cancer cells. Furthermore, treatment with ADDA 5 led to significant inhibition of tumor growth in flank xenograft mouse models. Importantly, ADDA 5 inhibited CcO activity and blocked cell proliferation and neurosphere formation in cultures of glioma stem cells, the cells implicated in tumor recurrence and resistance to therapy in patients with glioblastoma. In summary, we have identified ADDA 5 as a lead CcO inhibitor for further optimization as a novel approach for the treatment of glioblastoma and related cancers.

  12. Monocyte ADAM17 promotes diapedesis during transendothelial migration: identification of steps and substrates targeted by metalloproteinases.

    Science.gov (United States)

    Tsubota, Yoshiaki; Frey, Jeremy M; Tai, Phillip W L; Welikson, Robert E; Raines, Elaine W

    2013-04-15

    Despite expanded definition of the leukocyte adhesion cascade and mechanisms underlying individual steps, very little is known about regulatory mechanisms controlling sequential shifts between steps. We tested the hypothesis that metalloproteinases provide a mechanism to rapidly transition monocytes between different steps. Our study identifies diapedesis as a step targeted by metalloproteinase activity. Time-lapse video microscopy shows that the presence of a metalloproteinase inhibitor results in a doubling of the time required for human monocytes to complete diapedesis on unactivated or inflamed human endothelium, under both static and physiological-flow conditions. Thus, diapedesis is promoted by metalloproteinase activity. In contrast, neither adhesion of monocytes nor their locomotion over the endothelium is altered by metalloproteinase inhibition. We further demonstrate that metalloproteinase inhibition significantly elevates monocyte cell surface levels of integrins CD11b/CD18 (Mac-1), specifically during transendothelial migration. Interestingly, such alterations are not detected for other endothelial- and monocyte-adhesion molecules that are presumed metalloproteinase substrates. Two major transmembrane metalloproteinases, a disintegrin and metalloproteinase (ADAM)17 and ADAM10, are identified as enzymes that control constitutive cleavage of Mac-1. We further establish that knockdown of monocyte ADAM17, but not endothelial ADAM10 or ADAM17 or monocyte ADAM10, reproduces the diapedesis delay observed with metalloproteinase inhibition. Therefore, we conclude that monocyte ADAM17 facilitates the completion of transendothelial migration by accelerating the rate of diapedesis. We propose that the progression of diapedesis may be regulated by spatial and temporal cleavage of Mac-1, which is triggered upon interaction with endothelium.

  13. Construction of a rice glycoside hydrolase phylogenomic database and identification of targets for biofuel research

    Directory of Open Access Journals (Sweden)

    Rita eSharma

    2013-08-01

    Full Text Available Glycoside hydrolases (GH catalyze the hydrolysis of glycosidic bonds in cell wall polymers and can have major effects on cell wall architecture. Taking advantage of the massive datasets available in public databases, we have constructed a rice phylogenomic database of GHs (http://ricephylogenomics.ucdavis.edu/cellwalls/gh/. This database integrates multiple data types including the structural features, orthologous relationships, mutant availability and gene expression patterns for each GH family in a phylogenomic context. The rice genome encodes 437 GH genes classified into 34 families. Based on pairwise comparison with eight dicot and four monocot genomes, we identified 138 GH genes that are highly diverged between monocots and dicots, 57 of which have diverged further in rice as compared with four monocot genomes scanned in this study. Chromosomal localization and expression analysis suggest a role for both whole-genome and localized gene duplications in expansion and diversification of GH families in rice. We examined the meta-profiles of expression patterns of GH genes in twenty different anatomical tissues of rice. Transcripts of 51 genes exhibit tissue or developmental stage-preferential expression, whereas, seventeen other genes preferentially accumulate in actively growing tissues. When queried in RiceNet, a probabilistic functional gene network that facilitates functional gene predictions, nine out of seventeen genes form a regulatory network with the well-characterized genes involved in biosynthesis of cell wall polymers including cellulose synthase and cellulose synthase-like genes of rice. Two-thirds of the GH genes in rice are up regulated in response to biotic and abiotic stress treatments indicating a role in stress adaptation. Our analyses identify potential GH targets for cell wall modification.

  14. Escherichia coli genome-wide promoter analysis: Identification of additional AtoC binding target elements

    Directory of Open Access Journals (Sweden)

    Kolisis Fragiskos N

    2011-05-01

    Full Text Available Abstract Background Studies on bacterial signal transduction systems have revealed complex networks of functional interactions, where the response regulators play a pivotal role. The AtoSC system of E. coli activates the expression of atoDAEB operon genes, and the subsequent catabolism of short-chain fatty acids, upon acetoacetate induction. Transcriptome and phenotypic analyses suggested that atoSC is also involved in several other cellular activities, although we have recently reported a palindromic repeat within the atoDAEB promoter as the single, cis-regulatory binding site of the AtoC response regulator. In this work, we used a computational approach to explore the presence of yet unidentified AtoC binding sites within other parts of the E. coli genome. Results Through the implementation of a computational de novo motif detection workflow, a set of candidate motifs was generated, representing putative AtoC binding targets within the E. coli genome. In order to assess the biological relevance of the motifs and to select for experimental validation of those sequences related robustly with distinct cellular functions, we implemented a novel approach that applies Gene Ontology Term Analysis to the motif hits and selected those that were qualified through this procedure. The computational results were validated using Chromatin Immunoprecipitation assays to assess the in vivo binding of AtoC to the predicted sites. This process verified twenty-two additional AtoC binding sites, located not only within intergenic regions, but also within gene-encoding sequences. Conclusions This study, by tracing a number of putative AtoC binding sites, has indicated an AtoC-related cross-regulatory function. This highlights the significance of computational genome-wide approaches in elucidating complex patterns of bacterial cell regulation.

  15. Target organ identification of jellyfish envenomation using systemic and integrative analyses in anesthetized dogs.

    Science.gov (United States)

    Kang, Changkeun; Kim, Young Ki; Lee, Hyunkyoung; Cha, Mijin; Sohn, Eun-Tae; Jung, Eun-Sun; Song, Chiyoun; Kim, Minkyung; Lee, Hee Chun; Kim, Jong-Shu; Hwang, Jin-Yong; Yoon, Won Duk; Kim, Euikyung

    2011-01-01

    Proper treatment of jellyfish envenomed patients can be successfully achieved only from an understanding of the overall functional changes and alterations in physiological parameters under its envenomation. The majority of previous investigations on jellyfish venoms have covered only a couple of parameters at a time. Unlike most other fragmentary jellyfish studies, we employed an integrative toxicological approach, including hemodynamics, clinical chemistry and hematology analyses, using N. nomurai jellyfish venom (NnV) in dogs. After the baseline measurements for mean arterial pressure (MAP), cardiac output (CO) and heart rate (HR), NnV was intravenously administered to the dogs at doses of 0.1 or 0.3mg/kg body weight. The dogs showed significant decreases in MAP (-27.4±3.7 and -48.1±9.9 mmHg), CO (-1.1±0.1 L/min and -1.0±0.2 L/min), and HR (-4.5±0.3 and -9.9±3.1 beats/min) comparing with the respective baseline controls. The onset of systemic hypotension and bradycardia occurred within 1 min of NnV injection and they lasted for 1-35 min, depending on the NnV doses. Interestingly, serum biochemical analyses of envenomed dogs exhibited dramatic increases of alkaline phosphatase (ALP), creatine phosphokinase (CPK), alanine aminotransferase (ALT) and aspartate aminotransferase (AST), indicating its possible target organs. In conclusion, we have demonstrated simultaneously, for the first time, the multiple organ toxicities (cardiotoxic, myotoxic and hepatotoxic) of a scyphozoan jellyfish venom. Based on these results, an integrative toxinological approach using dogs appears to be effective in predicting jellyfish venom toxicities and designing their therapeutic strategies. We expect this method can be applied to other jellyfish venom research as well.

  16. Identification and Validation of Small-Gatekeeper Kinases as Drug Targets in Giardia lamblia

    Science.gov (United States)

    Hennessey, Kelly M.; Smith, Tess R.; Xu, Jennifer W.; Alas, Germain C. M.; Ojo, Kayode K.; Merritt, Ethan A.

    2016-01-01

    Giardiasis is widely acknowledged to be a neglected disease in need of new therapeutics to address toxicity and resistance issues associated with the limited available treatment options. We examined seven protein kinases in the Giardia lamblia genome that are predicted to share an unusual structural feature in their active site. This feature, an expanded active site pocket resulting from an atypically small gatekeeper residue, confers sensitivity to “bumped” kinase inhibitors (BKIs), a class of compounds that has previously shown good pharmacological properties and minimal toxicity. An initial phenotypic screen for biological activity using a subset of an in-house BKI library found that 5 of the 36 compounds tested reduced trophozoite growth by at least 50% at a concentration of 5 μM. The cellular localization and the relative expression levels of the seven protein kinases of interest were determined after endogenously tagging the kinases. Essentiality of these kinases for parasite growth and infectivity were evaluated genetically using morpholino knockdown of protein expression to establish those that could be attractive targets for drug design. Two of the kinases were critical for trophozoite growth and attachment. Therefore, recombinant enzymes were expressed, purified and screened against a BKI library of >400 compounds in thermal stability assays in order to identify high affinity compounds. Compounds with substantial thermal stabilization effects on recombinant protein were shown to have good inhibition of cell growth in wild-type G. lamblia and metronidazole-resistant strains of G. lamblia. Our data suggest that BKIs are a promising starting point for the development of new anti-giardiasis therapeutics that do not overlap in mechanism with current drugs. PMID:27806042

  17. Identification of vitamin D3 target genes in human breast cancer tissue.

    Science.gov (United States)

    Sheng, Lei; Anderson, Paul H; Turner, Andrew G; Pishas, Kathleen I; Dhatrak, Deepak J; Gill, Peter G; Morris, Howard A; Callen, David F

    2016-11-01

    Multiple epidemiological studies have shown that high vitamin D3 status is strongly associated with improved breast cancer survival. To determine the molecular pathways influenced by 1 alpha, 25-dihydroxyvitamin D3 (1,25D) in breast epithelial cells we isolated RNA from normal human breast and cancer tissues treated with 1,25D in an ex vivo explant system. RNA-Seq revealed 523 genes that were differentially expressed in breast cancer tissues in response to 1,25D treatment, and 127 genes with altered expression in normal breast tissues. GoSeq KEGG pathway analysis revealed 1,25D down-regulated cellular metabolic pathways and enriched pathways involved with intercellular adhesion. The highly 1,25D up-regulated target genes CLMN, SERPINB1, EFTUD1, and KLK6were selected for further analysis and up-regulation by 1,25D was confirmed by qRT-PCR analysis in breast cancer cell lines and in a subset of human clinical samples from normal and cancer breast tissues. Ketoconazole potentiated 1,25D-mediated induction of CLMN, SERPINB1, and KLK6 mRNA through inhibition of 24-hydroxylase (CYP24A1) activity. Elevated expression levels of CLMN, SERPINB1, and KLK6 are associated with prolonged relapse-free survival for breast cancer patients. The major finding of the present study is that exposure of both normal and malignant breast tissue to 1,25D results in changes in cellular adhesion, metabolic pathways and tumor suppressor-like pathways, which support epidemiological data suggesting that adequate vitamin D3 levels may improve breast cancer outcome.

  18. Identification of potential target genes for the tomato fruit-ripening regulator RIN by chromatin immunoprecipitation

    Directory of Open Access Journals (Sweden)

    Nakano Toshitsugu

    2011-01-01

    Full Text Available Abstract Background During ripening, climacteric fruits increase their ethylene level and subsequently undergo various physiological changes, such as softening, pigmentation and development of aroma and flavor. These changes occur simultaneously and are caused by the highly synchronized expression of numerous genes at the onset of ripening. In tomatoes, the MADS-box transcription factor RIN has been regarded as a key regulator responsible for the onset of ripening by acting upstream of both ethylene- and non-ethylene-mediated controls. However, except for LeACS2, direct targets of RIN have not been clarified, and little is known about the transcriptional cascade for ripening. Results Using immunoprecipitated (IPed DNA fragments recovered by chromatin immunoprecipitation (ChIP with anti-RIN antibody from ripening tomato fruit, we analyzed potential binding sites for RIN (CArG-box sites in the promoters of representative ripening-induced genes by quantitative PCR. Results revealed nearly a 5- to 20-fold enrichment of CArG boxes in the promoters of LeACS2, LeACS4, PG, TBG4, LeEXP1, and LeMAN4 and of RIN itself, indicating direct interaction of RIN with their promoters in vivo. Moreover, sequence analysis and genome mapping of 51 cloned IPed DNAs revealed potential RIN binding sites. Quantitative PCR revealed that four of the potential binding sites were enriched 4- to 17-fold in the IPed DNA pools compared with the controls, indicating direct interaction of RIN with these sites in vivo. Near one of the four CArG boxes we found a gene encoding a protein similar to thioredoxin y1. An increase in the transcript level of this gene was observed with ripening in normal fruit but not in the rin mutant, suggesting that RIN possibly induces its expression. Conclusions The presented results suggest that RIN controls fruit softening and ethylene production by the direct transcriptional regulation of cell-wall-modifying genes and ethylene biosynthesis genes

  19. The Fur regulon in anaerobically grown Salmonella enterica sv. Typhimurium: identification of new Fur targets

    Directory of Open Access Journals (Sweden)

    Porwollik Steffen

    2011-10-01

    B regulation, while serving to repress the expression of hmpA. Furthermore, Fur is required for the proper expression and activation of the antioxidant enzymes, FeSOD and MnSOD. Finally, this work identified twenty-six new targets of Fur regulation, and demonstrates that H-NS repressed genes are down-regulated in Δfur.

  20. Arylamine N-acetyltransferases--from drug metabolism and pharmacogenetics to identification of novel targets for pharmacological intervention.

    Science.gov (United States)

    Sim, Edith; Fakis, Giannoulis; Laurieri, Nicola; Boukouvala, Sotiria

    2012-01-01

    Arylamine N-acetyltransferases (NATs) are defined as xenobiotic metabolizing enzymes, adding an acetyl group from acetyl coenzyme A (CoA) to arylamines and arylhydrazines. NATs are found in organisms from bacteria and fungi to vertebrates. Several isoenzymes, often polymorphic, may be present in one organism. There are two functional polymorphic NATs in humans and polymorphisms in NAT2 underpinned pharmacogenetics as a discipline. NAT enzymes have had a role in important metabolic concepts: the identification of acetyl-CoA and endogenous metabolic roles in bacteria and in eukaryotic folate metabolism. In fungi, NAT is linked to formation of unique metabolites. A broad and exciting canvas of investigations has emerged over the past five years from fundamental studies on NAT enzymes. The role of human NAT1 in breast cancer where it is a biomarker and possible therapeutic target may also underlie NAT's early appearance during mammalian fetal development. Studies of NAT in Mycobacterium tuberculosis have identified potential therapeutic targets for tuberculosis whilst the role of NATs in fungi opens up potential toxicological intervention in agriculture. These developments are possible through the combination of genomics, enzymology and structural data. Strong binding of CoA to Bacillis anthracis NAT may point to divergent roles of NATs amongst organisms as does differential control of mammalian NAT gene expression. The powerful combination of phenotypic investigation following genetic manipulation of NAT genes from mice to mycobacteria has been coupled with generation of isoenzyme-specific inhibitors. This battery of molecular and systems biology approaches heralds a new era for NAT research in pharmacology and toxicology. Copyright © 2012 Elsevier Inc. All rights reserved.

  1. Identification of bacteria associated with underground parts of Crocus sativus by 16S rRNA gene targeted metagenomic approach.

    Science.gov (United States)

    Ambardar, Sheetal; Sangwan, Naseer; Manjula, A; Rajendhran, J; Gunasekaran, P; Lal, Rup; Vakhlu, Jyoti

    2014-10-01

    Saffron (Crocus sativus L), an autumn-flowering perennial sterile plant, reproduces vegetatively by underground corms. Saffron has biannual corm-root cycle that makes it an interesting candidate to study microbial dynamics in its rhizosphere and cormosphere (area under influence of corm). Culture independent 16S rRNA gene metagenomic study of rhizosphere and cormosphere of Saffron during flowering stage revealed presence of 22 genera but none of the genus was common in all the three samples. Bulk soil bacterial community was represented by 13 genera with Acidobacteria being dominant. In rhizosphere, out of eight different genera identified, Pseudomonas was the most dominant genus. Cormosphere bacteria comprised of six different genera, dominated by the genus Pantoea. This study revealed that the bacterial composition of all the three samples is significantly different (P < 0.05) from each other. This is the first report on the identification of bacteria associated with rhizosphere, cormosphere and bulk soil of Saffron, using cultivation independent 16S rRNA gene targeted metagenomic approach.

  2. Pax6 interactions with chromatin and identification of its novel direct target genes in lens and forebrain.

    Directory of Open Access Journals (Sweden)

    Qing Xie

    Full Text Available Pax6 encodes a specific DNA-binding transcription factor that regulates the development of multiple organs, including the eye, brain and pancreas. Previous studies have shown that Pax6 regulates the entire process of ocular lens development. In the developing forebrain, Pax6 is expressed in ventricular zone precursor cells and in specific populations of neurons; absence of Pax6 results in disrupted cell proliferation and cell fate specification in telencephalon. In the pancreas, Pax6 is essential for the differentiation of α-, β- and δ-islet cells. To elucidate molecular roles of Pax6, chromatin immunoprecipitation experiments combined with high-density oligonucleotide array hybridizations (ChIP-chip were performed using three distinct sources of chromatin (lens, forebrain and β-cells. ChIP-chip studies, performed as biological triplicates, identified a total of 5,260 promoters occupied by Pax6. 1,001 (133 of these promoter regions were shared between at least two (three distinct chromatin sources, respectively. In lens chromatin, 2,335 promoters were bound by Pax6. RNA expression profiling from Pax6⁺/⁻ lenses combined with in vivo Pax6-binding data yielded 76 putative Pax6-direct targets, including the Gaa, Isl1, Kif1b, Mtmr2, Pcsk1n, and Snca genes. RNA and ChIP data were validated for all these genes. In lens cells, reporter assays established Kib1b and Snca as Pax6 activated and repressed genes, respectively. In situ hybridization revealed reduced expression of these genes in E14 cerebral cortex. Moreover, we examined differentially expressed transcripts between E9.5 wild type and Pax6⁻/⁻ lens placodes that suggested Efnb2, Fat4, Has2, Nav1, and Trpm3 as novel Pax6-direct targets. Collectively, the present studies, through the identification of Pax6-direct target genes, provide novel insights into the molecular mechanisms of Pax6 gene control during mouse embryonic development. In addition, the present data demonstrate that Pax6

  3. RAS - Target Identification - Informatics

    Science.gov (United States)

    The RAS Informatics lab group develops tools to track and analyze “big data” from the RAS Initiative, as well as analyzes data from external projects. By integrating internal and external data, this group helps improve understanding of RAS-driven cancers.

  4. Fast Identification of Near-Trench Earthquakes Along the Mexican Subduction Zone Based on Characteristics of Ground Motion in Mexico City

    Science.gov (United States)

    Perez-Campos, X.; Singh, S. K.; Arroyo, D.; Rodríguez, Q.; Iglesias, A.

    2015-12-01

    The disastrous 1985 Michoacan earthquake gave rise to a seismic alert system for Mexico City which became operational in 1991. Initially limited to earthquakes along the Guerrero coast, the system now has a much wider coverage. Also, the 2004 Sumatra earthquake exposed the need for a tsunami early warning along the Mexican subduction zone. A fast identification of near-trench earthquakes along this zone may be useful in issuing a reliable early tsunami alert. The confusion caused by low PGA for the magnitude of an earthquake, leading to "missed" seismic alert, would be averted if its near-trench origin can be quickly established. It may also help reveal the spatial extent and degree of seismic coupling on the near-trench portion of the plate interface. This would lead to a better understanding of tsunami potential and seismic hazard along the Mexican subduction zone. We explore three methods for quick detection of near-trench earthquakes, testing them on recordings of 65 earthquakes at station CU in Mexico City (4.8 ≤Mw≤8.0; 270≤R≤615 km). The first method is based on the ratio of total to high-frequency energy, ER (Shapiro et al., 1998). The second method is based on parameter Sa*(6) which is the pseudo-acceleration response spectrum with 5% damping, Sa, at 6 s normalized by the PGA. The third parameter is the PGA residual, RESN, at CU, with respect to a newly-derived ground motion prediction equation at CU for coastal shallow-dipping thrust earthquakes following a bayesian approach. Since the near-trench earthquakes are relatively deficient in high-frequency radiation, we expect ER and Sa*(6) to be relatively large and RESN to be negative for such events. Tests on CU recordings show that if ER ≥ 100 and/or Sa*(6) ≥ 0.70, then the earthquake is near trench; for these events RESN ≤ 0. Such an event has greater tsunami potential. Few misidentifications and missed events are most probably a consequence of poor location, although unusual depth and source

  5. Identification of the bacterial protein FtsX as a unique target of chemokine-mediated antimicrobial activity against Bacillus anthracis

    OpenAIRE

    Matthew A Crawford; Lowe, David E.; Fisher, Debra J.; Stibitz, Scott; Plaut, Roger D; Beaber, John W.; Zemansky, Jason; Mehrad, Borna; Glomski, Ian J.; Strieter, Robert M.; Hughes, Molly A

    2011-01-01

    Chemokines are a family of chemotactic cytokines that function in host defense by orchestrating cellular movement during infection. In addition to this function, many chemokines have also been found to mediate the direct killing of a range of pathogenic microorganisms through an as-yet-undefined mechanism. As an understanding of the molecular mechanism and microbial targets of chemokine-mediated antimicrobial activity is likely to lead to the identification of unique, broad-spectrum therapeut...

  6. Novel sequential ChIP and simplified basic ChIP protocols for promoter co-occupancy and target gene identification in human embryonic stem cells

    OpenAIRE

    Elayaperumal Anuratha; Goh Saik-Kia; Jadrich Joy; Coley Kristen; Hoium Brian; Papenfuss Kate J; Medeiros Ricardo B; Herrera Julio E; Resnik Ernesto; Ni Hsiao-Tzu

    2009-01-01

    Abstract Background The investigation of molecular mechanisms underlying transcriptional regulation, particularly in embryonic stem cells, has received increasing attention and involves the systematic identification of target genes and the analysis of promoter co-occupancy. High-throughput approaches based on chromatin immunoprecipitation (ChIP) have been widely used for this purpose. However, these approaches remain time-consuming, expensive, labor-intensive, involve multiple steps, and requ...

  7. Identification of the bacterial protein FtsX as a unique target of chemokine-mediated antimicrobial activity against Bacillus anthracis

    OpenAIRE

    Crawford, Matthew A.; Lowe, David E.; Fisher, Debra J.; Stibitz, Scott; Roger D Plaut; Beaber, John W.; Zemansky, Jason; Mehrad, Borna; Glomski, Ian J.; Strieter, Robert M.; Hughes, Molly A.

    2011-01-01

    Chemokines are a family of chemotactic cytokines that function in host defense by orchestrating cellular movement during infection. In addition to this function, many chemokines have also been found to mediate the direct killing of a range of pathogenic microorganisms through an as-yet-undefined mechanism. As an understanding of the molecular mechanism and microbial targets of chemokine-mediated antimicrobial activity is likely to lead to the identification of unique, broad-spectrum therapeut...

  8. Cy5 maleimide labelling for sensitive detection of free thiols in native protein extracts: identification of seed proteins targeted by barley thioredoxin h isoforms.

    Science.gov (United States)

    Maeda, Kenji; Finnie, Christine; Svensson, Birte

    2004-03-01

    Barley thioredoxin h isoforms HvTrxh1 and HvTrxh2 differ in temporal and spatial distribution and in kinetic properties. Target proteins of HvTrxh1 and HvTrxh2 were identified in mature seeds and in seeds after 72 h of germination. Improvement of the established method for identification of thioredoxin-targeted proteins based on two-dimensional electrophoresis and fluorescence labelling of thiol groups was achieved by application of a highly sensitive Cy5 maleimide dye and large-format two-dimensional gels, resulting in a 10-fold increase in the observed number of labelled protein spots. The technique also provided information about accessible thiol groups in the proteins identified in the barley seed proteome. In total, 16 different putative target proteins were identified from 26 spots using tryptic in-gel digestion, matrix-assisted laser-desorption ionization-time-of-flight MS and database search. HvTrxh1 and HvTrxh2 were shown to have similar target specificity. Barley alpha-amylase/subtilisin inhibitor, previously demonstrated to be reduced by both HvTrxh1 and HvTrxh2, was among the identified target proteins, confirming the suitability of the method. Several alpha-amylase/trypsin inhibitors, some of which are already known as target proteins of thioredoxin h, and cyclophilin known as a target protein of m-type thioredoxin were also identified. Lipid transfer protein, embryospecific protein, three chitinase isoenzymes, a single-domain glyoxalase-like protein and superoxide dismutase were novel identifications of putative target proteins, suggesting new physiological roles of thioredoxin h in barley seeds.

  9. Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing

    Science.gov (United States)

    Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; Meng, Patrick; Xie, Lei

    2016-01-01

    Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and

  10. Identification of MCAM/CD146 as the target antigen of a human monoclonal antibody that recognizes both epithelioid and sarcomatoid types of mesothelioma.

    Science.gov (United States)

    Bidlingmaier, Scott; He, Jiang; Wang, Yong; An, Feng; Feng, Jinjin; Barbone, Dario; Gao, Dongwei; Franc, Ben; Broaddus, V Courtney; Liu, Bin

    2009-02-15

    The prognosis for patients diagnosed with mesothelioma is generally poor, and currently available treatments are usually ineffective. Therapies that specifically target tumor cells hold much promise for the treatment of cancers that are resistant to current approaches. We have previously selected phage antibody display libraries on mesothelioma cell lines to identify a panel of internalizing human single chain (scFv) antibodies that target mesothelioma-associated, clinically represented cell surface antigens and further exploited the internalizing function of these scFvs to specifically deliver lethal doses of liposome-encapsulated small molecule drugs to both epithelioid and sarcomatous subtypes of mesothelioma cells. Here, we report the identification of MCAM/MUC18/CD146 as the surface antigen bound by one of the mesothelioma-targeting scFvs using a novel cloning strategy based on yeast surface human proteome display. Immunohistochemical analysis of mesothelioma tissue microarrays confirmed that MCAM is widely expressed by both epithelioid and sarcomatous types of mesothelioma tumor cells in situ but not by normal mesothelial cells. In addition, quantum dot-labeled anti-MCAM scFv targets primary meosthelioma cells in tumor fragment spheroids cultured ex vivo. As the first step in evaluating the therapeutic potential of MCAM-targeting antibodies, we performed single-photon emission computed tomography studies using the anti-MCAM scFv and found that it recognizes mesothelioma organotypic xenografts in vivo. The combination of phage antibody library selection on tumor cells and rapid target antigen identification by screening the yeast surface-displayed human proteome could be a powerful method for mapping the targetable tumor cell surface epitope space.

  11. A large-scale identification of direct targets of the tomato MADS box transcription factor RIPENING INHIBITOR reveals the regulation of fruit ripening.

    Science.gov (United States)

    Fujisawa, Masaki; Nakano, Toshitsugu; Shima, Yoko; Ito, Yasuhiro

    2013-02-01

    The fruit ripening developmental program is specific to plants bearing fleshy fruits and dramatically changes fruit characteristics, including color, aroma, and texture. The tomato (Solanum lycopersicum) MADS box transcription factor RIPENING INHIBITOR (RIN), one of the earliest acting ripening regulators, is required for both ethylene-dependent and -independent ripening regulatory pathways. Recent studies have identified two dozen direct RIN targets, but many more RIN targets remain to be identified. Here, we report the large-scale identification of direct RIN targets by chromatin immunoprecipitation coupled with DNA microarray analysis (ChIP-chip) targeting the predicted promoters of tomato genes. Our combined ChIP-chip and transcriptome analysis identified 241 direct RIN target genes that contain a RIN binding site and exhibit RIN-dependent positive or negative regulation during fruit ripening, suggesting that RIN has both activator and repressor roles. Examination of the predicted functions of RIN targets revealed that RIN participates in the regulation of lycopene accumulation, ethylene production, chlorophyll degradation, and many other physiological processes. Analysis of the effect of ethylene using 1-methylcyclopropene revealed that the positively regulated subset of RIN targets includes ethylene-sensitive and -insensitive transcription factors. Intriguingly, ethylene is involved in the upregulation of RIN expression during ripening. These results suggest that tomato fruit ripening is regulated by the interaction between RIN and ethylene signaling.

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

    Directory of Open Access Journals (Sweden)

    Rosario Diaz

    2014-10-01

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

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

    Science.gov (United States)

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

    2014-10-01

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

  14. A multidisciplinary approach to the identification and evaluation of novel concepts for deeply buried hardened target defeat

    Science.gov (United States)

    Branscome, Ewell Caleb

    During the Cold War, Deeply Buried Hardened Targets (DBHTs) and the assets they protected were of great strategic and tactical concern to the Department of Defense. Megaton-class nuclear warheads were the only viable means of attacking many of these facilities, and even so, a small subset of DBHTs was anticipated to be robust even in the face of such an attack. Post Cold War, the threat posed by DBHTs has not disappeared. Rather, the conventional warfare advantages of the United States have led to an increasing emphasis by potential adversaries on the construction and use of hardened facilities such as DBHTs for protection of both conventional and unconventional assets. Further, the shift in perceived relative risk to the United States' national security from large scale all-out nuclear attack towards very limited attack by Weapons of Mass Destruction (WMD) has led some to hypothesize that "self-deterrence" may diminish the strategic value of current inventory nuclear weapons. The objective of the work described was to identify and explore a paradigm shifting solution that could offer leap-ahead capabilities to counter current and future DBHT threats while mitigating or eliminating the "self-deterrence" issue. Systematic evaluation of DHBT defeat alternatives lead to the selection of a thermal subterrene as a hypothetical means of providing such a capability. A number of possible implementation alternatives for a thermal subterrene were investigated, resulting in the identification of the RadioIsotope Powered Thermal Penetrator (RIPTP) concept for providing an effectively unlimited hard rock penetration capability using near-term technologies. However, the proposed approach was novel and thus required formulation and application of a physics based multidisciplinary analysis code to enable evaluation of lv design alternatives and analysis of performance. Technical considerations identified as important to the feasibility of a RIPTP for DBHT defeat included: packing

  15. 越野环境中无人驾驶车的障碍目标识别%Obstacle Identification in Cross-Country Environment for Unmanned Ground Vehicles

    Institute of Scientific and Technical Information of China (English)

    赵一兵; 郭烈; 张明恒; 李琳辉

    2011-01-01

    针对无人驾驶车环境感知技术,基于D-S证据理论融合多传感器信息,旨在解决障碍物身份识别技术难点.基于CCD和激光传感器建立信息融合系统,并提取每种障碍物的5个特征证据,包括距离对比度特征、平行四边形特征、边缘形状特征、灰度纹理特征和颜色特征.再根据目标类型和环境加权系数选择经验公式,通过模糊插值法求取身份隶属度近似获得各特征对目标的相关系数构造基本概率赋值函数.最后制定Dempster组合规则,融合多传感器特征信息识别障碍身份.试验表明本文方法能够准确有效地获取基本概率赋值函数,D-S证据理论融合方法提高了障碍物身份识别的准确性和鲁棒性.%Autonomous navigation in cross-country environments presents many new challenges including obstacle perception for unmanned ground vehicle. A new method suitable for recognizing obstacle is proposed. The first step is to build the sensor fusion system by using sensors such as CCD and ladar, then to extract five different types of features, including distance contrast, parallelogram rate, edge-shape-factor, gray texture and HSV value. The experiment formula is selected according to the types of obstacle and weight efficiency to calculate basic probability assignment (BPA). The subordinatien to each event in identification framework is obtained by using the fuzzy interpolation. It is supposed that the subordination is equal to correlation coefficient in the formula. Finally, dempster rules are used to integrate sensors information and the obstacle is recognized based on the D-S theory of evidence. The test results indicate that the resolution of BPA is correct, thus improving the validity and robustness of cross-country environment perception based on the new method.

  16. Target identification of grape seed extract in colorectal cancer using drug affinity responsive target stability (DARTS) technique: role of endoplasmic reticulum stress response proteins.

    Science.gov (United States)

    Derry, Molly M; Somasagara, Ranganatha R; Raina, Komal; Kumar, Sushil; Gomez, Joe; Patel, Manisha; Agarwal, Rajesh; Agarwal, Chapla

    2014-01-01

    Various natural agents, including grape seed extract (GSE), have shown considerable chemopreventive and anti-cancer efficacy against different cancers in pre-clinical studies; however, their specific protein targets are largely unknown and thus, their clinical usefulness is marred by limited scientific evidences about their direct cellular targets. Accordingly, herein, employing, for the first time, the recently developed drug affinity responsive target stability (DARTS) technique, we aimed to profile the potential protein targets of GSE in human colorectal cancer (CRC) cells. Unlike other methods, which can cause chemical alteration of the drug components to allow for detection, this approach relies on the fact that a drug bound protein may become less susceptible to proteolysis and hence the enriched proteins can be detected by Mass Spectroscopy methods. Our results, utilizing the DARTS technique followed by examination of the spectral output by LC/MS and the MASCOT data, revealed that GSE targets endoplasmic reticulum (ER) stress response proteins resulting in overall down regulation of proteins involved in translation and that GSE also causes oxidative protein modifications, specifically on methionine amino acids residues on its protein targets. Corroborating these findings, mechanistic studies revealed that GSE indeed caused ER stress and strongly inhibited PI3k-Akt-mTOR pathway for its biological effects in CRC cells. Furthermore, bioenergetics studies indicated that GSE also interferes with glycolysis and mitochondrial metabolism in CRC cells. Together, the present study identifying GSE molecular targets in CRC cells, combined with its efficacy in vast pre-clinical CRC models, further supports its usefulness for CRC prevention and treatment.

  17. A novel neural network based image reconstruction model with scale and rotation invariance for target identification and classification for Active millimetre wave imaging

    Science.gov (United States)

    Agarwal, Smriti; Bisht, Amit Singh; Singh, Dharmendra; Pathak, Nagendra Prasad

    2014-12-01

    Millimetre wave imaging (MMW) is gaining tremendous interest among researchers, which has potential applications for security check, standoff personal screening, automotive collision-avoidance, and lot more. Current state-of-art imaging techniques viz. microwave and X-ray imaging suffers from lower resolution and harmful ionizing radiation, respectively. In contrast, MMW imaging operates at lower power and is non-ionizing, hence, medically safe. Despite these favourable attributes, MMW imaging encounters various challenges as; still it is very less explored area and lacks suitable imaging methodology for extracting complete target information. Keeping in view of these challenges, a MMW active imaging radar system at 60 GHz was designed for standoff imaging application. A C-scan (horizontal and vertical scanning) methodology was developed that provides cross-range resolution of 8.59 mm. The paper further details a suitable target identification and classification methodology. For identification of regular shape targets: mean-standard deviation based segmentation technique was formulated and further validated using a different target shape. For classification: probability density function based target material discrimination methodology was proposed and further validated on different dataset. Lastly, a novel artificial neural network based scale and rotation invariant, image reconstruction methodology has been proposed to counter the distortions in the image caused due to noise, rotation or scale variations. The designed neural network once trained with sample images, automatically takes care of these deformations and successfully reconstructs the corrected image for the test targets. Techniques developed in this paper are tested and validated using four different regular shapes viz. rectangle, square, triangle and circle.

  18. A reference substance free diagnostic fragment ion-based approach for rapid identification of non-target components in Pudilan Xiaoyan oral liquid by high resolution mass spectrometry.

    Science.gov (United States)

    Dai, Chen; Wang, Chong; Zhang, Chunhua; Wang, Guoxiang; Wang, Jin; Chen, Jun; Guo, Bin; Yang, Tianshu; Cai, Bo

    2016-05-30

    Rapid and reliable identification of non-target components in herbal preparations remains a primary challenge, especially when corresponding reference substances are inaccessible. In this work, an efficient post-experiment data processing methodology, named reference substance free diagnostic fragment ion (RSFDFI), was developed based on ultra-high-performance liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC/LTQ-Orbitrap). The first step of this approach was to cluster the components that share common fragment ions into several groups. After querying the database using a predicted chemical formula, the component with the fewest primary hits was preferentially deduced based on its MS/MS spectrum. Once the structure was characterized, its common fragment ions could be used as the prior structural information to select the possible candidates that would facilitate the subsequent identification for each group. Taking Pudilan Xiaoyan oral liquid (PDL) as a model herbal preparation, which has been extensively used for the treatment of epidemic parotitis and children with hand-foot-mouth diseases, this strategy enables a nearly eight-fold narrowing of the database hits, with fifty-two components, including lignans, flavonoids, alkaloids and steroids, being rapidly identified. In conclusion, our work clearly demonstrates that integrating RSFDFI with high-resolution mass spectrometry is a powerful methodology for rapid identification of non-target components from herbal prescriptions and may open new avenues for chemical analysis in other complex mixtures.

  19. Proteome mining for the identification and in-silico characterization of putative drug targets of multi-drug resistant Clostridium difficile strain 630.

    Science.gov (United States)

    Lohani, Mohtashim; Dhasmana, Anupam; Haque, Shafiul; Wahid, Mohd; Jawed, Arshad; Dar, Sajad A; Mandal, Raju K; Areeshi, Mohammed Y; Khan, Saif

    2017-05-01

    Clostridium difficile is an enteric pathogen that causes approximately 20% to 30% of antibiotic-associated diarrhea. In recent years, there has been a substantial rise in the rate of C. difficile infections as well as the emergence of virulent and antibiotic resistant C. difficile strains. So, there is an urgent need for the identification of therapeutic potential targets and development of new drugs for the treatment and prevention of C. difficile infections. In the current study, we used a hybrid approach by combining sequence similarity-based approach and protein-protein interaction network topology-based approach to identify and characterize the potential drug targets of C. difficile. A total of 155 putative drug targets of C. difficile were identified and the metabolic pathway analysis of these putative drug targets using DAVID revealed that 46 of them are involved in 9 metabolic pathways. In-silico characterization of these proteins identified seven proteins involved in pathogen-specific peptidoglycan biosynthesis pathway. Three promising targets viz. homoserine dehydrogenase, aspartate-semialdehyde dehydrogenase and aspartokinase etc. were found to be involved in multiple enzymatic pathways of the pathogen. These 3 drug targets are of particular interest as they can be used for developing effective drugs against multi-drug resistant C. difficile strain 630 in the near future.

  20. Clinical spectrum of food allergy in children in Australia and South-East Asia: identification and targets for treatment.

    Science.gov (United States)

    Hill, D J; Hosking, C S; Heine, R G

    1999-08-01

    modification, particularly that of breastfeeding mothers whose infants present with colic before the age of 6 weeks, alleviated symptoms. Colic associated with vomiting has been attributed to gastro-oesophageal reflux (GOR). This has been considered primarily a motility disorder, but a secondary form resulting from food protein intolerance has been described recently. We have also recently identified a group of infants with distressed behaviour attributed to GOR who have failed to respond to H2-receptor antagonists, prokinetic agents and multiple formula changes. Symptoms resolved on commencement of an elemental amino acid-based formula. In two-thirds of the patients, symptoms relapsed when challenged with low-allergen soy formula or extensively hydrolysed formula. We propose that a period of food protein intolerance is a part of the normal development of the immune system as it encounters common dietary proteins in infancy and early childhood. Future targets for research are development of appropriate dietary and management strategies for these entities and identification of genetic markers for these disorders.

  1. Simultaneous identification and DNA barcoding of six Eimeria species infecting turkeys using PCR primers targeting the mitochondrial cytochrome c oxidase subunit I (mtCOI) locus.

    Science.gov (United States)

    Hafeez, Mian A; Shivaramaiah, Srichaitanya; Dorsey, Kristi Moore; Ogedengbe, Mosun E; El-Sherry, Shiem; Whale, Julia; Cobean, Julie; Barta, John R

    2015-05-01

    Species-specific PCR primers targeting the mitochondrial cytochrome c oxidase subunit I (mtCOI) locus were generated that allow for the specific identification of the most common Eimeria species infecting turkeys (i.e., Eimeria adenoeides, Eimeria meleagrimitis, Eimeria gallopavonis, Eimeria meleagridis, Eimeria dispersa, and Eimeria innocua). PCR reaction chemistries were optimized with respect to divalent cation (MgCl2) and dNTP concentrations, as well as PCR cycling conditions (particularly anneal temperature for primers). Genomic DNA samples from single oocyst-derived lines of six Eimeria species were tested to establish specificity and sensitivity of these newly designed primer pairs. A mixed 60-ng total DNA sample containing 10 ng of each of the six Eimeria species was used as DNA template to demonstrate specific amplification of the correct product using each of the species-specific primer pairs. Ten nanograms of each of the five non-target Eimeria species was pooled to provide a non-target, control DNA sample suitable to test the specificity of each primer pair. The amplifications of the COI region with species-specific primer pairs from pooled samples yielded products of expected sizes (209 to 1,012 bp) and no amplification of non-target Eimeria sp. DNA was detected using the non-target, control DNA samples. These primer pairs specific for Eimeria spp. of turkeys did not amplify any of the seven Eimeria species infecting chickens. The newly developed PCR primers can be used as a diagnostic tool capable of specifically identifying six turkey Eimeria species; additionally, sequencing of the PCR amplification products yields sequence-based genotyping data suitable for identification and molecular phylogenetics.

  2. Cis-regulatory element-based genome-wide identification of DREB1/CBF targets in Arabidopsis

    Institute of Scientific and Technical Information of China (English)

    Huan Zhao; Weizhong Liu; Yong Hu; Xianglin Liu; Yikun He

    2008-01-01

    Microarray analysis is used to identify transcriptional targets.However,the direct targets of transcription factors cannot be distin guished from indirect ones;further,genes with low-expression levels cannot be identified by this method.In the present study,we exploi the cis-element dehydration-responsive element(DRE)that is known to be responsible for the transcription of DRE binding factor](DREB1)targets in the promoter region of all Arabidopsis genes.Putative targets whose promoters contain the elements were verified by both microarray and reverse transcription-polymerase chain reaction(RT-PCR)analysis.Five new DREB 1/CBF direct targets were identified.Compared with traditional microarray analysis,our method is convenient and cost-effective for identifying the downstream targets of transcription factors.

  3. A computational method for identification of vaccine targets from protein regions of conserved human leukocyte antigen binding

    DEFF Research Database (Denmark)

    Olsen, Lars Rønn; Simon, Christian; Kudahl, Ulrich J.;

    2015-01-01

    target diverse regions in highly variable viral pathogens and this diversity may need to be addressed through redefinition of suitable peptide targets. Methods: We have developed a method for antigen assessment and target selection for polyvalent vaccines, with which we identified immune epitopes from...... the number of potential vaccine targets compared to the number of targets discovered using the traditional approach where low-frequency peptides are excluded. Conclusions: We developed a webserver with an intuitive visualization scheme for summarizing the T cell-based antigenic potential of any given protein......Background: Computational methods for T cell-based vaccine target discovery focus on selection of highly conserved peptides identified across pathogen variants, followed by prediction of their binding of human leukocyte antigen molecules. However, experimental studies have shown that T cells often...

  4. Rapid and accurate identification of Mycobacterium tuberculosis complex and common non-tuberculous mycobacteria by multiplex real-time PCR targeting different housekeeping genes.

    Science.gov (United States)

    Nasr Esfahani, Bahram; Rezaei Yazdi, Hadi; Moghim, Sharareh; Ghasemian Safaei, Hajieh; Zarkesh Esfahani, Hamid

    2012-11-01

    Rapid and accurate identification of mycobacteria isolates from primary culture is important due to timely and appropriate antibiotic therapy. Conventional methods for identification of Mycobacterium species based on biochemical tests needs several weeks and may remain inconclusive. In this study, a novel multiplex real-time PCR was developed for rapid identification of Mycobacterium genus, Mycobacterium tuberculosis complex (MTC) and the most common non-tuberculosis mycobacteria species including M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and the M. gordonae in three reaction tubes but under same PCR condition. Genetic targets for primer designing included the 16S rDNA gene, the dnaJ gene, the gyrB gene and internal transcribed spacer (ITS). Multiplex real-time PCR was setup with reference Mycobacterium strains and was subsequently tested with 66 clinical isolates. Results of multiplex real-time PCR were analyzed with melting curves and melting temperature (T (m)) of Mycobacterium genus, MTC, and each of non-tuberculosis Mycobacterium species were determined. Multiplex real-time PCR results were compared with amplification and sequencing of 16S-23S rDNA ITS for identification of Mycobacterium species. Sensitivity and specificity of designed primers were each 100 % for MTC, M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and M. gordonae. Sensitivity and specificity of designed primer for genus Mycobacterium was 96 and 100 %, respectively. According to the obtained results, we conclude that this multiplex real-time PCR with melting curve analysis and these novel primers can be used for rapid and accurate identification of genus Mycobacterium, MTC, and the most common non-tuberculosis Mycobacterium species.

  5. Identification of CETP as a molecular target for estrogen positive breast cancer cell death by cholesterol depleting agents

    OpenAIRE

    Esau, Luke; Sagar, Sunil; Bangarusamy, Dhinoth; Kaur, Mandeep

    2016-01-01

    Cholesterol and its metabolites act as steroid hormone precursors, which promote estrogen receptor positive (ER+) breast cancer (BC) progression. Development of cholesterol targeting anticancer drugs has been hindered due to the lack of knowledge of viable molecular targets. Till now, Cholesteryl ester transfer protein (CETP) has been envisaged as a feasible molecular target in atherosclerosis, but for the first time, we show that CETP contributes to BC cell survival when challenged with chol...

  6. Strand Analysis, a free online program for the computational identification of the best RNA interference (RNAi targets based on Gibbs free energy

    Directory of Open Access Journals (Sweden)

    Tiago Campos Pereira

    2007-01-01

    Full Text Available The RNA interference (RNAi technique is a recent technology that uses double-stranded RNA molecules to promote potent and specific gene silencing. The application of this technique to molecular biology has increased considerably, from gene function identification to disease treatment. However, not all small interfering RNAs (siRNAs are equally efficient, making target selection an essential procedure. Here we present Strand Analysis (SA, a free online software tool able to identify and classify the best RNAi targets based on Gibbs free energy (deltaG. Furthermore, particular features of the software, such as the free energy landscape and deltaG gradient, may be used to shed light on RNA-induced silencing complex (RISC activity and RNAi mechanisms, which makes the SA software a distinct and innovative tool.

  7. Identification of Cellular Targets of MicroRNA-181a in HepG2 Cells: A New Approach for Functional Analysis of MicroRNAs.

    Science.gov (United States)

    Tan, Jane Yi Lin; Habib, Nagy A; Chuah, York Wieo; Yau, Yin Hoe; Geifman-Shochat, Susana; Chen, Wei Ning

    2015-01-01

    MicroRNAs (miRNAs) are known to play a part in regulating important cellular processes. They generally perform their regulatory function through their binding with mRNAs, ultimately leading to a repression of target protein expression levels. However, their roles in cellular processes are poorly understood due to the limited understanding of their specific cellular targets. Aberrant levels of miRNAs have been found in hepatocellular carcinoma (HCC) including miR-181a. Using bioinformatics analysis, cyclin-dependent kinase inhibitor 1B (CDKN1β) and transcriptional factor E2F7 were identified as potential targets of miR-181a. Validation analysis using surface plasmon resonance (SPR) showed a positive binding between miR-181a and the 3'UTRs of these two potential mRNA targets. In vivo luciferase assay further confirmed the positive miR-181a:mRNA bindings, where a significant decrease in luciferase activity was detected when HepG2 cells were co-transfected with the 3'UTR-containing reporter plasmids and miR-181a. The potential impact of miR-181a binding to its specific targets on the general cellular behavior was further investigated. Results showed that miR-181a significantly activated the MAPK/JNK pathway which regulates cell proliferation, supporting our recently reported findings. Inhibition of miR-181a, on the other hand, abolished the observed activation. Our findings open up a new approach in designing targeted functional analysis of miRNAs in cellular processes, through the identification of their cellular targets.

  8. Detection Performance Assessment of Ground-Based Phased Array Radar for Ballistic Targets%地基相控阵雷达对弹道目标的探测性能评估

    Institute of Scientific and Technical Information of China (English)

    李星星; 姚汉英; 孙文峰

    2014-01-01

    为解决地基相控阵雷达对弹道目标探测的最优部署问题,建立弹道中段目标轨道运动和进动模型,提出弹道中段多部地基相控阵雷达的弹道目标探测概率模型,以及平均检测概率、稳定跟踪时间和资源冗余时间3种组合的雷达探测性能评估指标。依据弹道目标RCS及探测距离随观测时间的变化情况,通过仿真实验对多种部署方式下地基雷达对弹道目标探测性能评估指标的分析,得出的结论为弹道导弹防御系统中地基雷达的部署方式提供了有效的参考依据。%In order to solve the optimal deployment problem of ground-based phased array radar in detecting ballistic targets,the orbit motion and precession motion models of ballistic targets were built up,and the detection probability model for ballistic targets by using several ground-based phased array radars was proposed.Three evaluation indexes of radars'detection performance were given: average detection probability,stable tracking time and resource redundancy time .According to the variation of RCS and detection range for ballistic targets in midcourse,detection performance evaluation indexes of several radar deployment schemes were analyzed through experiments .The conclusion in this paper may provide some reference for deploying the ground-based radar in ballistic missile defense (BMD) system for targets'optimal detection.

  9. Identification of off-target cleavage sites of zinc finger nucleases and TAL effector nucleases using predictive models.

    Science.gov (United States)

    Fine, Eli J; Cradick, Thomas J; Bao, Gang

    2014-01-01

    Using engineered nucleases, such as Zinc Finger Nucleases (ZFNs) or Transcription Activator-Like Effector Nucleases (TALENs), to make targeted genomic modifications has become a common technique to create new model organisms and custom cell lines, and has shown great promise for disease treatment. However, these nucleases have the potential for off-target cleavage that could confound interpretation of experimental results and be detrimental for therapeutic use. Here, we describe a method to test for nuclease cleavage at potential off-target sites predicted by bioinformatics models.

  10. Development and validation of a multiplex real-time PCR method to simultaneously detect 47 targets for the identification of genetically modified organisms.

    Science.gov (United States)

    Cottenet, Geoffrey; Blancpain, Carine; Sonnard, Véronique; Chuah, Poh Fong

    2013-08-01

    Considering the increase of the total cultivated land area dedicated to genetically modified organisms (GMO), the consumers' perception toward GMO and the need to comply with various local GMO legislations, efficient and accurate analytical methods are needed for their detection and identification. Considered as the gold standard for GMO analysis, the real-time polymerase chain reaction (RTi-PCR) technology was optimised to produce a high-throughput GMO screening method. Based on simultaneous 24 multiplex RTi-PCR running on a ready-to-use 384-well plate, this new procedure allows the detection and identification of 47 targets on seven samples in duplicate. To comply with GMO analytical quality requirements, a negative and a positive control were analysed in parallel. In addition, an internal positive control was also included in each reaction well for the detection of potential PCR inhibition. Tested on non-GM materials, on different GM events and on proficiency test samples, the method offered high specificity and sensitivity with an absolute limit of detection between 1 and 16 copies depending on the target. Easy to use, fast and cost efficient, this multiplex approach fits the purpose of GMO testing laboratories.

  11. A novel targeted proteomics method for identification and relative quantitation of difference in nitration degree of OGDH between healthy and diabetic mouse.

    Science.gov (United States)

    Yu, Qing; Liu, Bin; Ruan, Dandan; Niu, Chao; Shen, Jiayi; Ni, Maowei; Cong, Weitao; Lu, Xianghong; Jin, Litai

    2014-11-01

    For analysis of nitration modification of α oxoglutarate dehydrogenase (α-OGDH) induced by diabetes, a targeted proteomics strategy was developed through the use of Skyline. All peptides containing Y and W of the target proteins were nitrated in silico and output to produce parallel reaction monitoring (PRM) or SRM method for nitration analysis. A nitrated casein mixture was used as standard protein to assess the feasibility of this method. The results demonstrated the availability of this strategy for nitration identification, and subsequently this method was used to analyze the nitration of α-OGDH from myocardial tissue extracts of diabetic mouse. The PRM method was primarily generated by Skyline for identification of the actual nitrated peptides from all possible nitrated peptides of α-OGDH due to the complexity of α-OGDH. The PRM-based data were analyzed by SEQUEST, and transitions of the identified nitrated peptides were used to develop an SRM method for relative quantitation of nitration degree. The nitration degree of α-OGDH for diabetic mouse is higher than that for control mouse, indicating that α-OGDH of the diabetic mouse suffered from more intense oxidative damage. We believe that this approach for obtaining information regarding nitration will facilitate the study of other PTMs in complex mixtures. © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  12. Identification of targets of miR-200b by a SILAC-based quantitative proteomic approach

    Directory of Open Access Journals (Sweden)

    Arivusudar Marimuthu

    2014-09-01

    Full Text Available miRNAs regulate gene expression by binding to cognate mRNAs causing mRNA degradation or translational repression. Mass spectrometry-based proteomic analysis is being widely used to identify miRNA targets. The miR-200b miRNA cluster is often overexpressed in multiple cancer types, but the identity of the targets remains elusive. Using SILAC-based analysis, we examined the effects of overexpression of a miR-200b mimic or a control miRNA in fibrosarcoma cells. We identified around 300 potential targets of miR-200b based on a change in the expression of protein levels. We validated a subset of potential targets at the transcript level using quantitative PCR.

  13. Systematic Identification and Assessment of Therapeutic Targets for Breast Cancer Based on Genome-Wide RNA Interference Transcriptomes

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2017-02-01

    Full Text Available With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration. We first establish the reference gene expression profiles from breast cancer cell line MCF7 upon genome-wide RNA interference (RNAi of a total of 3689 genes, and the breast cancer query signatures using RNA-seq data generated from tissue samples of clinical breast cancer patients in the Cancer Genome Atlas (TCGA. Based on gene set enrichment analysis, we identified a set of 510 genes that when knocked down could significantly reverse the transcriptome of breast cancer state. We then perform multifaceted assessment to analyze the gene set to prioritize potential targets for gene therapy. We also propose drug repurposing opportunities and identify potentially druggable proteins that have been poorly explored with regard to the discovery of small-molecule modulators. Finally, we obtained a small list of candidate therapeutic targets for four major breast cancer subtypes, i.e., luminal A, luminal B, HER2+ and triple negative breast cancer. This RNAi transcriptome-based approach can be a helpful paradigm for relevant researches to identify and prioritize candidate targets for experimental validation.

  14. Computational identification and characterization of conserved miRNAs and their target genes in garlic (Allium sativum L.) expressed sequence tags.

    Science.gov (United States)

    Panda, Debashis; Dehury, Budheswar; Sahu, Jagajjit; Barooah, Madhumita; Sen, Priyabrata; Modi, Mahendra K

    2014-03-10

    The endogenous small non-coding functional microRNAs (miRNAs) are short in size, range from ~21 to 24 nucleotides in length, play a pivotal role in gene expression in plants and animals by silencing genes either by destructing or blocking of translation of homologous mRNA. Although various high-throughput, time consuming and expensive techniques like forward genetics and direct cloning are employed to detect miRNAs in plants but comparative genomics complemented with novel bioinformatic tools pave the way for efficient and cost-effective identification of miRNAs through homologous sequence search with previously known miRNAs. In this study, an attempt was made to identify and characterize conserved miRNAs in garlic expressed sequence tags (ESTs) through computational means. For identification of novel miRNAs in garlic, a total 3227 known mature miRNAs of plant kingdom Viridiplantae were searched for homology against 21,637 EST sequences resulting in identification of 6 potential miRNA candidates belonging to 6 different miRNA families. The psRNATarget server predicted 33 potential target genes and their probable functions for the six identified miRNA families in garlic. Most of the garlic miRNA target genes seem to encode transcription factors as well as genes involved in stress response, metabolism, plant growth and development. The results from the present study will shed more light on the understanding of molecular mechanisms of miRNA in garlic which may aid in the development of novel and precise techniques to understand some post-transcriptional gene silencing mechanism in response to stress tolerance.

  15. Integrating Small RNA Sequencing with QTL Mapping for Identification of miRNAs and Their Target Genes Associated with Heat Tolerance at the Flowering Stage in Rice

    Science.gov (United States)

    Liu, Qing; Yang, Tifeng; Yu, Ting; Zhang, Shaohong; Mao, Xingxue; Zhao, Junliang; Wang, Xiaofei; Dong, Jingfang; Liu, Bin

    2017-01-01

    Although, microRNAs (miRNAs) have been reported to be associated with heat tolerance at the seedling stage in rice, their involvement in heat tolerance at the flowering stage is still unknown. In this study, small RNA profiling was conducted in a heat-tolerant variety Gan-Xiang-Nuo (GXN) and a heat-sensitive variety Hua-Jing-Xian-74 (HJX), respectively. Totally, 102 miRNAs were differentially expressed (DE) under heat stress. Compared to HJX, GXN had more DE miRNAs and its DE miRNAs changed earlier under heat stress. Plant Ontology (PO) analysis of the target genes revealed that many DE miRNAs were involved in flower development. As a parallel experiment, QTL mapping was also conducted and four QTLs for heat tolerance at the flowering stage were identified using chromosome single-segment substitution lines derived from GXN and HJX. Further, through integrating analysis of DE miRNAs with QTLs, we identified 8 target genes corresponding to 26 miRNAs within the four QTL regions. Some meaningful target genes such as LOC_Os12g42400, SGT1, and pectinesterase were within the QTL regions. The negative correlation between miR169r-5p and its target gene LOC_Os12g42400 was confirmed under heat stress, and overexpression of miR169r-5p enhanced heat tolerance at flowering stage in rice. Our results demonstrate that the integrated analysis of genome-wide miRNA profiling with QTL mapping can facilitate identification of miRNAs and their target genes associated with the target traits and the limited candidates identified in this study offer an important source for further functional analysis and molecular breeding for heat tolerance in rice. PMID:28174587

  16. 历史人物伦理思想的指认依据--以梁漱溟为例%Identification grounds of historical figures’ ethical thoughts:Taking Liang Shuming as an example

    Institute of Scientific and Technical Information of China (English)

    廖济忠; 李建华

    2015-01-01

    堪称伦理思想者,当有指认依据在。以梁漱溟为例,提出伦理思想的三个指认依据:一是基本稳定的形上基础;二是相对系统的伦理主张;三是较为广泛的实际影响。只有坚持论从史出,我们才有可能靠近历史人物伦理思想的历史真实和价值真实。%Whether one can be rated as an ethical thinker or not, there should be some identification grounds. By taking Liang Shuming as an example, this paper proposes three identification grounds of ethical thoughts: basically stable metaphysical foundation, relatively systematic ethical proposition, and comparatively extensive and actual influence. Only by adhering to theory coming from historical materials, can we approach historical truth and value truth of historical figures’ ethical thoughts.

  17. Identification of putative drug targets in Vancomycin-resistant Staphylococcus aureus (VRSA) using computer aided protein data analysis.

    Science.gov (United States)

    Hasan, Md Anayet; Khan, Md Arif; Sharmin, Tahmina; Hasan Mazumder, Md Habibul; Chowdhury, Afrin Sultana

    2016-01-01

    Vancomycin-resistant Staphylococcus aureus (VRSA) is a Gram-positive, facultative aerobic bacterium which is evolved from the extensive exposure of Vancomycin to Methicillin resistant S. aureus (MRSA) that had become the most common cause of hospital and community-acquired infections. Due to the emergence of different antibiotic resistance strains, there is an exigency to develop novel drug targets to address the provocation of multidrug-resistant bacteria. In this study, in-silico genome subtraction methodology was used to design potential and pathogen specific drug targets against VRSA. Our study divulged 1987 proteins from the proteome of 34,549 proteins, which have no homologues in human genome after sequential analysis through CD-HIT and BLASTp. The high stringency analysis of the remaining proteins against database of essential genes (DEG) resulted in 169 proteins which are essential for S. aureus. Metabolic pathway analysis of human host and pathogen by KAAS at the KEGG server sorted out 19 proteins involved in unique metabolic pathways. 26 human non-homologous membrane-bound essential proteins including 4 which were also involved in unique metabolic pathway were deduced through PSORTb, CELLO v.2.5, ngLOC. Functional classification of uncharacterized proteins through SVMprot derived 7 human non-homologous membrane-bound hypothetical essential proteins. Study of potential drug target against Drug Bank revealed pbpA-penicillin-binding protein 1 and hypothetical protein MQW_01796 as the best drug target candidate. 2D structure was predicted by PRED-TMBB, 3D structure and functional analysis was also performed. Protein-protein interaction network of potential drug target proteins was analyzed by using STRING. The identified drug targets are expected to have great potential for designing novel drugs against VRSA infections and further screening of the compounds against these new targets may result in the discovery of novel therapeutic compounds that can be

  18. Identification of direct serum-response factor gene targets during Me2SO-induced P19 cardiac cell differentiation.

    Science.gov (United States)

    Zhang, Shu Xing; Garcia-Gras, Eduardo; Wycuff, Diane R; Marriot, Suzanne J; Kadeer, Nijiati; Yu, Wei; Olson, Eric N; Garry, Daniel J; Parmacek, Michael S; Schwartz, Robert J

    2005-05-13

    Serum-response factor (SRF) is an obligatory transcription factor, required for the formation of vertebrate mesoderm leading to the origin of the cardiovascular system. Protein A-TEV-tagged chromatin immunoprecipitation technology was used to collect direct SRF-bound gene targets from pluripotent P19 cells, induced by Me2SO treatment into an enriched cardiac cell population. From 242 sequenced DNA fragments, we identified 188 genomic DNA fragments as potential direct SRF targets that contain CArG boxes and CArG-like boxes. Of the 92 contiguous genes that were identified, a subgroup of 43 SRF targets was then further validated by co-transfection assays with SRF. Expression patterns of representative candidate genes were compared with the LacZ reporter expression activity of the endogenous SRF gene. According to the Unigene data base, 84% of the SRF target candidates were expressed, at least, in the heart. In SRF null embryonic stem cells, 81% of these SRF target candidates were greatly affected by the absence of SRF. Among these SRF-regulated genes, Raf1, Map4k4, and Bicc1 have essential roles in mesoderm formation. The 12 regulated SRF target genes, Mapk10 (JNK3), Txnl2, Azi2, Tera, Sema3a, Lrp4, Actc1, Myl3, Hspg2, Pgm2, Hif3a, and Asb5, have been implicated in cardiovascular formation, and the Ski and Hes6 genes have roles in muscle differentiation. SRF target genes related to cell mitosis and cycle, E2f5, Npm1, Cenpb, Rbbp6, and Scyl1, expressed in the heart tissue were differentially regulated in SRF null ES cells.

  19. Identification of a novel peptide ligand targeting visceral adipose tissue via transdermal route by in vivo phage display.

    Science.gov (United States)

    Lee, Nam Kyung; Kim, Hong Shin; Kim, Kyung Hyun; Kim, Eun-Bae; Cho, Chong Su; Kang, Sang Kee; Choi, Yun Jaie

    2011-11-01

    To find novel peptide ligands targeting visceral adipose tissue (visceral fat) via transdermal route, in vivo phage display screening was conducted by dermal administration of a phage-peptide library to rats and a peptide sequence, CGLHPAFQC (designated as TDA1), was identified as a targeting ligand to visceral adipose tissue through the consecutive transdermal biopannings. Adipocyte-specific affinity and transdermal activity of the TDA1 were validated in vitro and targeting ability of the dermally administered TDA1 to visceral adipose tissue was also confirmed in vivo. TDA1 was effectively translocated into systemic circulation after dermal administration and selectively targeted visceral adipose tissue without any preference to other organs tested. Fluorescent microscopic analysis revealed that the TDA1 could be specifically localized in the hair follicles of the skin, as well as in the visceral adipose tissue. Thus, we inferred that dermally administered TDA1 would first access systemic circulation via hair follicles as its transdermal route and then could target visceral fat effectively. The overall results suggest that the TDA1 peptide could be potentially applied as a homing moiety for delivery of anti-obesity therapeutics to visceral fat through the convenient transdermal pathway.

  20. Identification, characterization and expression analysis of MicroRNAs and their targets in the potato (Solanum tuberosum).

    Science.gov (United States)

    Xie, Fuliang; Frazier, Taylor P; Zhang, Baohong

    2011-02-15

    MicroRNAs (miRNAs) are recognized as a class of important post-transcriptional expression regulators that act on their target genes by degradation of target mRNAs or by inhibition of target protein translation. Compared with the current numbers of identified miRNAs for other species in the plant kingdom, a large number of potential miRNAs remains to be identified in potato. In this study, using a newly modified comparative genome strategy, a total of 202 potential potato miRNAs were identified, which belong to 78 families. miR162, miR167, and miR396 are highly expressed in all tested organs. miR372 is highly expressed in flowers. A total of 1094 miRNA targets were predicted and some of them encode transcription factors as well as genes that function in stress response, signal transduction, and a variety of other metabolic processes. Gene ontology (GO) analysis implicates that these targets are involved in 545 biological processes. Of those processes, 28 are related to potato defense mechanisms against bacteria, viruses, and fungi, the metabolism of molecules such as carbon, sucrose, starch, and lipid, and the development of primary and lateral roots. Pathway enrichment analysis, based on the Kyoto Encyclopedia of Genes and Genomes (KEGG), demonstrates that the identified miRNAs participated in 98 metabolism networks, some of which include sucrose metabolism, fatty acid metabolism, amino acid metabolism, carbon fixation, and the biosynthesis of plant hormones.

  1. High-throughput identification of C/D box snoRNA targets with CLIP and RiboMeth-seq.

    Science.gov (United States)

    Gumienny, Rafal; Jedlinski, Dominik J; Schmidt, Alexander; Gypas, Foivos; Martin, Georges; Vina-Vilaseca, Arnau; Zavolan, Mihaela

    2017-03-17

    High-throughput sequencing has greatly facilitated the discovery of long and short non-coding RNAs (ncRNAs), which frequently guide ribonucleoprotein complexes to RNA targets, to modulate their metabolism and expression. However, for many ncRNAs, the targets remain to be discovered. In this study, we developed computational methods to map C/D box snoRNA target sites using data from core small nucleolar ribonucleoprotein crosslinking and immunoprecipitation and from transcriptome-wide mapping of 2΄-O-ribose methylation sites. We thereby assigned the snoRNA guide to a known methylation site in the 18S rRNA, we uncovered a novel partially methylated site in the 28S ribosomal RNA, and we captured a site in the 28S rRNA in interaction with multiple snoRNAs. Although we also captured mRNAs in interaction with snoRNAs, we did not detect 2΄-O-methylation of these targets. Our study provides an integrated approach to the comprehensive characterization of 2΄-O-methylation targets of snoRNAs in species beyond those in which these interactions have been traditionally studied and contributes to the rapidly developing field of 'epitranscriptomics'. © The Author(s) 2016. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Identification of multipath genes differentially expressed in pathway-targeted microarrays in zebrafish infected and surviving spring viremia carp virus (SVCV suggest preventive drug candidates.

    Directory of Open Access Journals (Sweden)

    Paloma Encinas

    Full Text Available Spring viremia carp virus (SVCV is a rhabdovirus seasonally affecting warm-water cyprinid fish farming causing high impacts in worldwide economy. Because of the lack of effective preventive treatments, the identification of multipath genes involved in SVCV infection might be an alternative to explore the possibilities of using drugs for seasonal prevention of this fish disease. Because the zebrafish (Danio rerio is a cyprinid susceptible to SVCV and their genetics and genome sequence are well advanced, it has been chosen as a model for SVCV infections. We have used newly designed pathway-targeted microarrays 3-4-fold enriched for immune/infection functional-relevant probes by using zebrafish orthologous to human genes from selected pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG. The comparative analysis of differential expression of genes through 20 pathways in 2-day exposed or 30-day survivors of SVCV infection allowed the identification of 16 multipath genes common to more than 6 pathways. In addition, receptors (Toll-like, B-cell, T-cell, RIG1-like as well as viral RNA infection pathways were identified as the most important human-like pathways targeted by SVCV infection. Furthermore, by using bioinformatic tools to compare the promoter sequences corresponding to up and downregulated multipath gene groups, we identified putative common transcription factors which might be controlling such responses in a coordinated manner. Possible drug candidates to be tested in fish, can be identified now through search of data bases among those associated with the human orthologous to the zebrafish multipath genes. With the use of pathway-targeted microarrays, we identified some of the most important genes and transcription factors which might be implicated in viral shutoff and/or host survival responses after SVCV infection. These results could contribute to develop novel drug-based prevention methods and consolidate the zebrafish/SVCV as a

  3. Identification of multipath genes differentially expressed in pathway-targeted microarrays in zebrafish infected and surviving spring viremia carp virus (SVCV) suggest preventive drug candidates.

    Science.gov (United States)

    Encinas, Paloma; Garcia-Valtanen, Pablo; Chinchilla, Blanca; Gomez-Casado, Eduardo; Estepa, Amparo; Coll, Julio

    2013-01-01

    Spring viremia carp virus (SVCV) is a rhabdovirus seasonally affecting warm-water cyprinid fish farming causing high impacts in worldwide economy. Because of the lack of effective preventive treatments, the identification of multipath genes involved in SVCV infection might be an alternative to explore the possibilities of using drugs for seasonal prevention of this fish disease. Because the zebrafish (Danio rerio) is a cyprinid susceptible to SVCV and their genetics and genome sequence are well advanced, it has been chosen as a model for SVCV infections. We have used newly designed pathway-targeted microarrays 3-4-fold enriched for immune/infection functional-relevant probes by using zebrafish orthologous to human genes from selected pathways of the Kyoto Encyclopedia of Genes and Genomes (KEGG). The comparative analysis of differential expression of genes through 20 pathways in 2-day exposed or 30-day survivors of SVCV infection allowed the identification of 16 multipath genes common to more than 6 pathways. In addition, receptors (Toll-like, B-cell, T-cell, RIG1-like) as well as viral RNA infection pathways were identified as the most important human-like pathways targeted by SVCV infection. Furthermore, by using bioinformatic tools to compare the promoter sequences corresponding to up and downregulated multipath gene groups, we identified putative common transcription factors which might be controlling such responses in a coordinated manner. Possible drug candidates to be tested in fish, can be identified now through search of data bases among those associated with the human orthologous to the zebrafish multipath genes. With the use of pathway-targeted microarrays, we identified some of the most important genes and transcription factors which might be implicated in viral shutoff and/or host survival responses after SVCV infection. These results could contribute to develop novel drug-based prevention methods and consolidate the zebrafish/SVCV as a model for

  4. Grounded theory.

    Science.gov (United States)

    Harris, Tina

    2015-04-29

    Grounded theory is a popular research approach in health care and the social sciences. This article provides a description of grounded theory methodology and its key components, using examples from published studies to demonstrate practical application. It aims to demystify grounded theory for novice nurse researchers, by explaining what it is, when to use it, why they would want to use it and how to use it. It should enable nurse researchers to decide if grounded theory is an appropriate approach for their research, and to determine the quality of any grounded theory research they read.

  5. Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

    Directory of Open Access Journals (Sweden)

    Bin Tang

    Full Text Available B-cell leukemia/lymphoma 11B (Bcl11b is a transcription factor showing predominant expression in the striatum. To date, there are no known gene targets of Bcl11b in the nervous system. Here, we define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq in combination with genome-wide expression profiling. Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b. ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene. Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified. Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic factor/neurotrophin signaling. Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b. These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders. Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.

  6. Investigate the rock mechanics aspects of potholes in the platinum mines, their contribution to poor ground conditions, and if proactive identification is possible

    CSIR Research Space (South Africa)

    Urcan, H

    2003-07-01

    Full Text Available The main aim of this project was to define and quantify the effect of potholes on ground conditions in platinum stopes, and assess whether these changes could be used to predict the occurrence of potholes ahead of stope faces. In order to gain...

  7. IDENTIFICATION OF OCEANOGRAPHIC PARAMETERS FOR DETERMINING PELAGIC TUNA FISHING GROUND IN THE NORTH PAPUA WATERS USING MULTI-SENSOR SATELLITE DATA

    Directory of Open Access Journals (Sweden)

    VlNCENTIUS SlREGAR

    2006-01-01

    Full Text Available The North Papua waters as one of the important fi shing grounds in the world contribute approximately 75% of world production of pelagic tunas. These fishing grounds are still determined by hunting method. This method is time consuming and costly. However, in many areas determination of fishing ground using satellited data lias been applied by detecting the important oceanographic parameter of the presence of fish schooling such as, sea surface temperature and chlorophyl. Mostly these parameters are used integrat edly. The aim of this study is to assess the important oceanographic parameters detected from mu lti-sensor satellites (NO AA/AVHRR, Seawifs and Topex Poisedon for determining fishing ground of pelagic tunas in the North Papua waters at east season. The parameters include Sea Surface Temperature (STT, chlorophyl-a and currents. The ava ilability of data from optic sensor (Seawifs: chl-a and AVHRR: Thermal is limited by the presence of cloud cover. In that case, Topex Poseidon satellite data can be used to provide the currents data. The integration of data from multi-sensors increases the availability of the oceanographic parameters for prediction of the potential fishing zones in the study area.

  8. Genome-wide identification of Brassica napus microRNAs and their targets in response to cadmium.

    Science.gov (United States)

    Zhou, Zhao Sheng; Song, Jian Bo; Yang, Zhi Min

    2012-07-01

    MicroRNAs (miRNAs) are a distinct class of small RNAs in plants that not only regulate biological processes but also regulate response to environmental stresses. The toxic heavy metal cadmium (Cd) induces expression of several miRNAs in rapeseed (Brassica napus), but it is not known on a genome-wide scale how the expression of miRNAs and their target genes, is regulated by Cd. In this study, four small RNA libraries and four degradome libraries were constructed from Cd-treated and non-Cd-treated roots and shoots of B. napus seedlings. Using high-throughput sequencing, the study identified 84 conserved and non-conserved miRNAs (belonging to 37 miRNA families) from Cd-treated and non-treated B. napus, including 19 miRNA members that were not identified before. Some of the miRNAs were validated by RNA gel blotting. Most of the identified miRNAs were found to be differentially expressed in roots/shoots or regulated by Cd exposure. The study simultaneously identified 802 targets for the 37 (24 conserved and 13 non-conserved) miRNA families, from which there are 200, 537, and 65 targets, belonging to categories I, II, and III, respectively. In category I alone, many novel targets for miRNAs were identified and shown to be involved in plant response to Cd.

  9. Identification of Thioredoxin Disulfide Targets Using a Quantitative Proteomics Approach Based on Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji;

    2008-01-01

    , protein extract of embryos from germinated barley seeds was treated +/- Trx, and thiols released from target protein disulfides were irreversibly blocked with iodoacetamide. The remaining cysteine residues in the Trx-treated and the control (-Trx) samples were then chemically reduced and labeled...

  10. PPARa: master regulator of lipid metabolism im mouse and human : identification of hepatic PPARa target genes by expression profiling

    NARCIS (Netherlands)

    Rakhshandehroo, M.

    2010-01-01

    The peroxisome proliferator activated receptor alpha (PPARα) is a ligand activated tran- scription factor involved in the regulation of a variety of processes, ranging from inflam- mation and immunity to nutrient metabolism and energy homeostasis. PPARα serves as a molecular target for hypolipidemic

  11. A brassinosteroid transcriptional network revealed by genome-wide identification of BESI target genes in Arabidopsis thaliana.

    Science.gov (United States)

    Yu, Xiaofei; Li, Lei; Zola, Jaroslaw; Aluru, Maneesha; Ye, Huaxun; Foudree, Andrew; Guo, Hongqing; Anderson, Sarah; Aluru, Srinivas; Liu, Peng; Rodermel, Steve; Yin, Yanhai

    2011-02-01

    Brassinosteroids (BRs) are important regulators for plant growth and development. BRs signal to control the activities of the BES1 and BZR1 family transcription factors. The transcriptional network through which BES1 and BZR regulate large number of target genes is mostly unknown. By combining chromatin immunoprecipitation coupled with Arabidopsis tiling arrays (ChIP-chip) and gene expression studies, we have identified 1609 putative BES1 target genes, 404 of which are regulated by BRs and/or in gain-of-function bes1-D mutant. BES1 targets contribute to BR responses and interactions with other hormonal or light signaling pathways. Computational modeling of gene expression data using Algorithm for the Reconstruction of Accurate Cellular Networks (ARACNe) reveals that BES1-targeted transcriptional factors form a gene regulatory network (GRN). Mutants of many genes in the network displayed defects in BR responses. Moreover, we found that BES1 functions to inhibit chloroplast development by repressing the expression of GLK1 and GLK2 transcription factors, confirming a hypothesis generated from the GRN. Our results thus provide a global view of BR regulated gene expression and a GRN that guides future studies in understanding BR-regulated plant growth.

  12. Identification and Functional Analysis of MicroRNAs and Their Targets in Platanus acerifolia under Lead (Pb Stress

    Directory of Open Access Journals (Sweden)

    Yuanlong Wang

    2015-03-01

    Full Text Available MicroRNAs (miRNAs play important regulatory roles in development and stress responses in plants. Lead (Pb is a non-essential element that is highly toxic to living organisms. Platanus acerifolia is grown as a street tree in cities throughout temperate regions for its importance in improving the urban ecological environment. MiRNAs that respond to abiotic stresses have been identified in plants; however, until now, the influence of Pb stress on P. acerifolia miRNAs has not been reported. To identify miRNAs and predict their target genes under Pb stress, two small RNA and two degradome libraries were constructed from Pb-treated and Pb-free leaves of P. acerifolia seedlings. After sequencing, 55 known miRNAs and 129 novel miRNAs were obtained, and 104 target genes for the miRNAs were identified by degradome sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to predict the functions of the targets. The expressions of eight differentially expressed miRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR. This is the first report about P. acerifolia miRNAs and their target genes under Pb stress. This study has provided data for further research into molecular mechanisms involved in resistance of P. acerifolia to Pb stress.

  13. Identification of CETP as a molecular target for estrogen positive breast cancer cell death by cholesterol depleting agents.

    Science.gov (United States)

    Esau, Luke; Sagar, Sunil; Bangarusamy, Dhinoth; Kaur, Mandeep

    2016-09-01

    Cholesterol and its metabolites act as steroid hormone precursors, which promote estrogen receptor positive (ER+) breast cancer (BC) progression. Development of cholesterol targeting anticancer drugs has been hindered due to the lack of knowledge of viable molecular targets. Till now, Cholesteryl ester transfer protein (CETP) has been envisaged as a feasible molecular target in atherosclerosis, but for the first time, we show that CETP contributes to BC cell survival when challenged with cholesterol depleting agents. We show that MCF-7 CETP knockout BC cells pose less resistance towards cytotoxic compounds (Tamoxifen and Acetyl Plumbagin (AP)), and were more susceptible to intrinsic apoptosis. Analysis of differentially expressed genes using Ingenuity Pathway Analysis (IPA), in vivo tumor inhibition, and in vitro phenotypic responses to AP revealed a unique CETP-centric cholesterol pathway involved in sensitizing ER+ BC cells to intrinsic mitochondrial apoptosis. Furthermore, analysis of cell line, tissue and patient data available in publicly available databases linked elevated CETP expression to cancer, cancer relapse and overall poor survival. Overall, our findings highlight CETP as a pharmacologically relevant and unexploited cellular target in BC. The work also highlights AP as a promising chemical entity for preclinical investigations as a cholesterol depleting anticancer therapeutic agent.

  14. Identification and Functional Analysis of MicroRNAs and Their Targets in Platanus acerifolia under Lead (Pb) Stress

    Science.gov (United States)

    Wang, Yuanlong; Zhao, Zhenli; Deng, Minjie; Liu, Rongning; Niu, Suyan; Fan, Guoqiang

    2015-01-01

    MicroRNAs (miRNAs) play important regulatory roles in development and stress responses in plants. Lead (Pb) is a non-essential element that is highly toxic to living organisms. Platanus acerifolia is grown as a street tree in cities throughout temperate regions for its importance in improving the urban ecological environment. MiRNAs that respond to abiotic stresses have been identified in plants; however, until now, the influence of Pb stress on P. acerifolia miRNAs has not been reported. To identify miRNAs and predict their target genes under Pb stress, two small RNA and two degradome libraries were constructed from Pb-treated and Pb-free leaves of P. acerifolia seedlings. After sequencing, 55 known miRNAs and 129 novel miRNAs were obtained, and 104 target genes for the miRNAs were identified by degradome sequencing. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses were performed to predict the functions of the targets. The expressions of eight differentially expressed miRNAs were validated by quantitative real-time polymerase chain reaction (qRT-PCR). This is the first report about P. acerifolia miRNAs and their target genes under Pb stress. This study has provided data for further research into molecular mechanisms involved in resistance of P. acerifolia to Pb stress. PMID:25830479

  15. Identification of poly(rC) binding protein 2 (PCBP2) as a target protein of immunosuppressive agent 15-deoxyspergualin

    Energy Technology Data Exchange (ETDEWEB)

    Murahashi, Masataka; Simizu, Siro; Morioka, Masahiko [Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522 (Japan); Umezawa, Kazuo, E-mail: umezawa@aichi-med-u.ac.jp [Department of Molecular Target Medicine, Aichi Medical University School of Medicine, 1-1 Yazako-Karimata, Nagakute 480-1195 (Japan)

    2016-08-05

    15-Deoxyspergualin (DSG) is an immunosuppressive agent being clinically used. Unlike tacrolimus and cyclosporine A, it does not inhibit the calcineurin pathway, and its mechanism of action and target molecule have not been elucidated. Therefore, we previously prepared biotinylated derivative of DSG (BDSG) to fish up the target protein. In the present research, we identified poly(rC) binding protein 2 (PCBP2) as a DSG-binding protein using this probe. DSG was confirmed to bind to PCBP2 by pull-down assay. Intracellular localization of PCBP2 was changed from the nucleus to the cytoplasm by DSG treatment. DSG inhibited the cell growth, and over-expression of PCBP2 reduced the anti-proliferative activity of DSG. PCBP2 is known to regulate various proteins including STAT1/2. Thus, we found PCBP2 as the first target protein of DSG that can explain the immunosuppressive activity. -- Highlights: •Fifteen-deoxyspergualin (DSG) is an immunosuppressive agent clinically used. •We have identified PCBP2, an RNA-binding protein, as a molecular target of DSG. •Alteration of PCBP2 activity may explain the immunosuppressive activity of DSG.

  16. Identification of Novel Target Genes of MADS-Box Transcription Factor RIN for Control of Fruit Ripening

    Institute of Scientific and Technical Information of China (English)

    Guozheng Qin; Yuying Wang; Baohua Cao; Weihao Wang; Shiping Tian

    2012-01-01

    MADS-box transcription factor RIN represents a global developmental regulator of fruit ripening.However,the specific set of genes modulated by RIN and the mechanisms underlying the transcription regulation remain largely unknown.To search for potential downstream targets of RIN,we compared the global protein expression of wild-type tomato fruits with rin mutant using mass-spectrometry-based proteomics.A total of 41 proteins associated with various biological processes were identified as the candidates.Gene expression analysis indicated that the protein levels were correlated well with the mRNA levels for most proteins.A search for transcription factor binding sites revealed various RIN sites in the promoters of genes encoding the differentially expressed proteins.Among the candidate target genes,five (E8,TomloxC,PNAE,PGK,and ADH2) were identified as direct targets of RIN by chromatin immunoprecipitation.Detection of in vitro protein-DNA interaction using electrophoretic mobility shift assay confirmed the binding ability of RIN to the promoters of these genes.Two of the direct target genes,TomloxC and ADH2,which encoding lipoxygenase (LOX) and alcohol dehydrogenase,respectively,are critical for the production of characteristic tomato aromas derived from LOX pathway.Further study indicated that RIN also directly regulated the expression of HPL that encodes hydroperoxide lyase,another rate-limiting enzyme in LOX pathway.Mutation of RIN resulted in the deregulation of LOX pathway,leading to specific defect in the generation of hexanal,trans-2-hexanal,hexenol,and cis-3-hexanol,the primary aroma compounds derived from LOX pathway,during fruit ripening.These results indicate that RIN modulates aroma formation via direct regulation of gene expression of LOX pathway.Taken together,our findings suggest that the regulatory effect of RIN in fruit ripening is achieved by targeting specific molecular pathways.

  17. Transcriptome-Wide Identification of miRNAs and Their Targets from Typha angustifolia by RNA-Seq and Their Response to Cadmium Stress.

    Science.gov (United States)

    Xu, Yingchun; Chu, Lingling; Jin, Qijiang; Wang, Yanjie; Chen, Xian; Zhao, Hui; Xue, Zeyun

    2015-01-01

    MicroRNAs (miRNAs) play important roles in plant responses to environmental stress. In this work, we used high-throughput sequencing to analyze transcriptome and small RNAs (sRNAs) in Typha angustifolia under cadmium (Cd) stress. 57,608,230 raw reads were obtained from deep sequencing of a pooled cDNA library. Sequence assembly and analysis yielded 102,473 unigenes. We subsequently sequenced two sRNA libraries from T. angustifolia with or without Cd exposure respectively. Based on transcriptome data of T. angustifolia, we catalogued and analyzed the sRNAs, resulting in the identification of 114 conserved miRNAs and 41 novel candidate miRNAs in both small RNA libraries. In silico analysis revealed 764 targets for 89 conserved miRNAs and 21 novel miRNAs. Statistical analysis on sequencing reads abundance and experimental validation revealed that 4 conserved and 6 novel miRNAs showed specific expression. Combined with function of target genes, these results suggested that miRNAs might play a role in plant Cd stress response. This study provided the first transcriptome-based analysis of miRNAs and their targets responsive to Cd stress in T. angustifolia, which provide a framework for further analysis of miRNAs and their role in regulating plant responses to Cd stress.

  18. Identification of potential drug targets by subtractive genome analysis of Escherichia coli O157:H7: an in silico approach

    Directory of Open Access Journals (Sweden)

    Mondal SI

    2015-12-01

    Full Text Available Shakhinur Islam Mondal,1,6,* Sabiha Ferdous,1,* Nurnabi Azad Jewel,1 Arzuba Akter,2,6 Zabed Mahmud,1 Md Muzahidul Islam,1 Tanzila Afrin,3 Nurul Karim4,5 1Genetic Engineering and Biotechnology Department, Shahjalal University of Science and Technology, Sylhet, Bangladesh; 2Biochemistry and Molecular Biology Department, Shahjalal University of Science and Technology, Sylhet, Bangladesh; 3Department of Pharmacy, East West University, Aftabnagar, Bangladesh; 4Biochemistry and Molecular Biology Department, Jahangirnagar University, Savar, Bangladesh; 5Division of Parasitology, 6Division of Microbiology, Department of Infectious Diseases, Faculty of Medicine, University of Miyazaki, Miyazaki, Japan *These authors contributed equally to this work Abstract: Bacterial enteric infections resulting in diarrhea, dysentery, or enteric fever constitute a huge public health problem, with more than a billion episodes of disease annually in developing and developed countries. In this study, the deadly agent of hemorrhagic diarrhea and hemolytic uremic syndrome, Escherichia coli O157:H7 was investigated with extensive computational approaches aimed at identifying novel and broad-spectrum antibiotic targets. A systematic in silico workflow consisting of comparative genomics, metabolic pathways analysis, and additional drug prioritizing parameters was used to identify novel drug targets that were essential for the pathogen’s survival but absent in its human host. Comparative genomic analysis of Kyoto Encyclopedia of Genes and Genomes annotated metabolic pathways identified 350 putative target proteins in E. coli O157:H7 which showed no similarity to human proteins. Further bioinformatic approaches including prediction of subcellular localization, calculation of molecular weight, and web-based investigation of 3D structural characteristics greatly aided in filtering the potential drug targets from 350 to 120. Ultimately, 44 non-homologous essential proteins of E

  19. A Ground Target Tracking Approach for UAVs with Intermittent Measurements%一种间断观测下的无人机地面目标跟踪方法

    Institute of Scientific and Technical Information of China (English)

    谢斌; 项志宇

    2011-01-01

    提出了一种基于贝叶斯滤波器和适航地图的跟踪算法(BF-Hmap),解决间断观测下的无人机地面目标跟踪问题.采用基于中心线和梯度图的快速道路提取算法生成目标适航地图,该图描述了地面目标与当前地形相关的运动能力.采用贝叶斯滤波器分两步在线更新目标状态的后验概率分布,即在预测阶段考虑适航地图对目标运动的约束,以及在估计阶段充分利用目标的所有观测信息.仿真结果表明,在间断观测下该算法对地面机动目标有着良好的跟踪效果.%A tracking algorithm using Bayesian filter and hospitability map (BF-HMap) is proposed to deal with the ground target tracking problem for unmanned aerial vehicles (UAVs) with intermittent measurements. The hospitability map, which describes the terrain-dependent motion capability of ground targets, is built through a centerline-and-gradient-based road detection method. The posterior probability density function (PDF) of the target state is maintained on-line through a Bayesian filter in two stages: the prediction stage takes into account the motion constraint provided by hospitability map and the estimation stage considers of all detection information that both the target is detected or not. Simulations show that the proposed approach provides a feasible solution to tracking maneuvering targets with intermittent measurements.

  20. Identification of therapeutic targets for Alzheimer's disease via differentially expressed gene and weighted gene co-expression network analyses.

    Science.gov (United States)

    Jia, Yujie; Nie, Kun; Li, Jing; Liang, Xinyue; Zhang, Xuezhu

    2016-11-01

    In order to investigate the pathogenic targets and associated biological process of Alzheimer's disease in the present study, mRNA expression profiles (GSE28146) and microRNA (miRNA) expression profiles (GSE16759) were downloaded from the Gene Expression Omnibus database. In GSE28146, eight control samples, and Alzheimer's disease samples comprising seven incipient, eight moderate, seven severe Alzheimer's disease samples, were included. The Affy package in R was used for background correction and normalization of the raw microarray data. The differentially expressed genes (DEGs) and differentially expressed miRNAs were identified using the Limma package. In addition, mRNAs were clustered using weighted gene correlation network analysis, and modules found to be significantly associated with the stages of Alzheimer's disease were screened out. The Database for Annotation, Visualization, and Integrated Discovery was used to perform Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway analyses. The target genes of the differentially expressed miRNAs were identified using the miRWalk database. Compared with the control samples, 175,59 genes and 90 DEGs were identified in the incipient, moderate and severe Alzheimer's disease samples, respectively. A module, which contained 1,592 genes was found to be closely associated with the stage of Alzheimer's disease and biological processes. In addition, pathways associated with Alzheimer's disease and other neurological diseases were found to be enriched in those genes. A total of 139 overlapped genes were identified between those genes and the DEGs in the three groups. From the miRNA expression profiles, 189 miRNAs were found differentially expressed in the samples from patients with Alzheimer's disease and 1,647 target genes were obtained. In addition, five overlapped genes were identified between those 1,647 target genes and the 139 genes, and these genes may be important pathogenic targets for Alzheimer

  1. Development of a qualitative real-time PCR method to detect 19 targets for identification of genetically modified organisms.

    Science.gov (United States)

    Peng, Cheng; Wang, Pengfei; Xu, Xiaoli; Wang, Xiaofu; Wei, Wei; Chen, Xiaoyun; Xu, Junfeng

    2016-01-01

    As the amount of commercially available genetically modified organisms (GMOs) grows recent years, the diversity of target sequences for molecular detection techniques are eagerly needed. Considered as the gold standard for GMO analysis, the real-time PCR technology was optimized to produce a high-throughput GMO screening method. With this method we can detect 19 transgenic targets. The specificity of the a