Airborne ladar man-in-the-loop operations in tactical environments

NASA Astrophysics Data System (ADS)

Grobmyer, Joseph E., Jr.; Lum, Tommy; Morris, Robert E.; Hard, Sarah J.; Pratt, H. L.; Florence, Tom; Peddycoart, Ed

2004-09-01

The U.S. Army Research, Development and Engineering Command (RDECOM) is developing approaches and processes that will exploit the characteristics of current and future Laser Radar (LADAR) sensor systems for critical man-in-the-loop tactical processes. The importance of timely and accurate target detection, classification, identification, and engagement for future combat systems has been documented and is viewed as a critical enabling factor for FCS survivability and lethality. Recent work has demonstrated the feasibility of using low cost but relatively capable personal computer class systems to exploit the information available in Ladar sensor frames to present the war fighter or analyst with compelling and usable imagery for use in the target identification and engagement processes in near real time. The advantages of LADAR imagery are significant in environments presenting cover for targets and the associated difficulty for automated target recognition (ATR) technologies.

A Camera-Based Target Detection and Positioning UAV System for Search and Rescue (SAR) Purposes

PubMed Central

Sun, Jingxuan; Li, Boyang; Jiang, Yifan; Wen, Chih-yung

2016-01-01

Wilderness search and rescue entails performing a wide-range of work in complex environments and large regions. Given the concerns inherent in large regions due to limited rescue distribution, unmanned aerial vehicle (UAV)-based frameworks are a promising platform for providing aerial imaging. In recent years, technological advances in areas such as micro-technology, sensors and navigation have influenced the various applications of UAVs. In this study, an all-in-one camera-based target detection and positioning system is developed and integrated into a fully autonomous fixed-wing UAV. The system presented in this paper is capable of on-board, real-time target identification, post-target identification and location and aerial image collection for further mapping applications. Its performance is examined using several simulated search and rescue missions, and the test results demonstrate its reliability and efficiency. PMID:27792156

A Camera-Based Target Detection and Positioning UAV System for Search and Rescue (SAR) Purposes.

PubMed

Sun, Jingxuan; Li, Boyang; Jiang, Yifan; Wen, Chih-Yung

2016-10-25

Wilderness search and rescue entails performing a wide-range of work in complex environments and large regions. Given the concerns inherent in large regions due to limited rescue distribution, unmanned aerial vehicle (UAV)-based frameworks are a promising platform for providing aerial imaging. In recent years, technological advances in areas such as micro-technology, sensors and navigation have influenced the various applications of UAVs. In this study, an all-in-one camera-based target detection and positioning system is developed and integrated into a fully autonomous fixed-wing UAV. The system presented in this paper is capable of on-board, real-time target identification, post-target identification and location and aerial image collection for further mapping applications. Its performance is examined using several simulated search and rescue missions, and the test results demonstrate its reliability and efficiency.

Real-Time Continuous Identification of Greenhouse Plant Pathogens Based on Recyclable Microfluidic Bioassay System.

PubMed

Qu, Xiangmeng; Li, Min; Zhang, Hongbo; Lin, Chenglie; Wang, Fei; Xiao, Mingshu; Zhou, Yi; Shi, Jiye; Aldalbahi, Ali; Pei, Hao; Chen, Hong; Li, Li

2017-09-20

The development of a real-time continuous analytical platform for the pathogen detection is of great scientific importance for achieving better disease control and prevention. In this work, we report a rapid and recyclable microfluidic bioassay system constructed from oligonucleotide arrays for selective and sensitive continuous identification of DNA targets of fungal pathogens. We employ the thermal denaturation method to effectively regenerate the oligonucleotide arrays for multiple sample detection, which could considerably reduce the screening effort and costs. The combination of thermal denaturation and laser-induced fluorescence detection technique enables real-time continuous identification of multiple samples (<10 min per sample). As a proof of concept, we have demonstrated that two DNA targets of fungal pathogens (Botrytis cinerea and Didymella bryoniae) can be sequentially analyzed using our rapid microfluidic bioassay system, which provides a new paradigm in the design of microfluidic bioassay system and will be valuable for chemical and biomedical analysis.

Laser radar range and detection performance for MEMS corner cube retroreflector arrays

NASA Astrophysics Data System (ADS)

Grasso, Robert J.; Odhner, Jefferson E.; Stewart, Hamilton; McDaniel, Robert V.

2004-12-01

BAE SYSTEMS reports on a program to characterize the performance of MEMS corner cube retroreflector arrays under laser illumination. These arrays have significant military and commercial application in the areas of: 1) target identification; 2) target tracking; 3) target location; 4) identification friend-or-foe (IFF); 5) parcel tracking, and; 6) search and rescue assistance. BAE SYSTEMS has theoretically determined the feasibility of these devices to learn if sufficient signal-to-noise performance exists to permit a cooperative laser radar sensor to be considered for device location and interrogation. Results indicate that modest power-apertures are required to achieve SNR performance consistent with high probability of detection and low false alarm rates.

Laser radar range and detection performance for MEMS corner cube retroreflector arrays

NASA Astrophysics Data System (ADS)

Grasso, Robert J.; Jost, Steven R.; Smith, M. J.; McDaniel, Robert V.

2004-01-01

BAE SYSTEMS reports on a program to characterize the performance of MEMS corner cube retroreflector arrays under laser illumination. These arrays have significant military and commercial application in the areas of: (1) target identification; (2) target tracking; (3) target location; (4) identification friend-or-foe (IFF); (5) parcel tracking, and; (6) search and rescue assistance. BAE SYSTEMS has theoretically determined the feasibility of these devices to learn if sufficient signal-to-noise performance exists to permit a cooperative laser radar sensor to be considered for device location and interrogation. Results indicate that modest power-apertures are required to achieve SNR performance consistent with high probability of detection and low false alarm rates.

Marine Air Traffic Control and Landing System (METCALS) Investigation.

DTIC Science & Technology

1982-02-01

as Identification Friend-or-Foe (IFF), was first developed and used by the military in World War II. Since then, IFF has been expanded and improved... identification and three dimensional target position accuracy. In addition, because this system employs a transponder, the signal strength loss with range... identification . The first two events can be used to state the MATCALS ASR operational goal in radar terms. This statement consists of two parts: (1

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification.

PubMed

Wu, Xunxun; Chen, Xiaofei; Dan, Jia; Cao, Yan; Gao, Shouhong; Guo, Zhiying; Zerbe, Philipp; Chai, Yifeng; Diao, Yong; Zhang, Lei

2016-05-06

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines.

Characterization of anti-leukemia components from Indigo naturalis using comprehensive two-dimensional K562/cell membrane chromatography and in silico target identification

PubMed Central

Wu, Xunxun; Chen, Xiaofei; Dan, Jia; Cao, Yan; Gao, Shouhong; Guo, Zhiying; Zerbe, Philipp; Chai, Yifeng; Diao, Yong; Zhang, Lei

2016-01-01

Traditional Chinese Medicine (TCM) has been developed for thousands of years and has formed an integrated theoretical system based on a large amount of clinical practice. However, essential ingredients in TCM herbs have not been fully identified, and their precise mechanisms and targets are not elucidated. In this study, a new strategy combining comprehensive two-dimensional K562/cell membrane chromatographic system and in silico target identification was established to characterize active components from Indigo naturalis, a famous TCM herb that has been widely used for the treatment of leukemia in China, and their targets. Three active components, indirubin, tryptanthrin and isorhamnetin, were successfully characterized and their anti-leukemia effects were validated by cell viability and cell apoptosis assays. Isorhamnetin, with undefined cancer related targets, was selected for in silico target identification. Proto-oncogene tyrosine-protein kinase (Src) was identified as its membrane target and the dissociation constant (Kd) between Src and isorhamnetin was 3.81 μM. Furthermore, anti-leukemia effects of isorhamnetin were mediated by Src through inducing G2/M cell cycle arrest. The results demonstrated that the integrated strategy could efficiently characterize active components in TCM and their targets, which may bring a new light for a better understanding of the complex mechanism of herbal medicines. PMID:27150638

Eccentricity error identification and compensation for high-accuracy 3D optical measurement

PubMed Central

He, Dong; Liu, Xiaoli; Peng, Xiang; Ding, Yabin; Gao, Bruce Z

2016-01-01

The circular target has been widely used in various three-dimensional optical measurements, such as camera calibration, photogrammetry and structured light projection measurement system. The identification and compensation of the circular target systematic eccentricity error caused by perspective projection is an important issue for ensuring accurate measurement. This paper introduces a novel approach for identifying and correcting the eccentricity error with the help of a concentric circles target. Compared with previous eccentricity error correction methods, our approach does not require taking care of the geometric parameters of the measurement system regarding target and camera. Therefore, the proposed approach is very flexible in practical applications, and in particular, it is also applicable in the case of only one image with a single target available. The experimental results are presented to prove the efficiency and stability of the proposed approach for eccentricity error compensation. PMID:26900265

Eccentricity error identification and compensation for high-accuracy 3D optical measurement.

PubMed

He, Dong; Liu, Xiaoli; Peng, Xiang; Ding, Yabin; Gao, Bruce Z

2013-07-01

The circular target has been widely used in various three-dimensional optical measurements, such as camera calibration, photogrammetry and structured light projection measurement system. The identification and compensation of the circular target systematic eccentricity error caused by perspective projection is an important issue for ensuring accurate measurement. This paper introduces a novel approach for identifying and correcting the eccentricity error with the help of a concentric circles target. Compared with previous eccentricity error correction methods, our approach does not require taking care of the geometric parameters of the measurement system regarding target and camera. Therefore, the proposed approach is very flexible in practical applications, and in particular, it is also applicable in the case of only one image with a single target available. The experimental results are presented to prove the efficiency and stability of the proposed approach for eccentricity error compensation.

Electromagnetic image guidance in gynecology: prospective study of a new laparoscopic imaging and targeting technique for the treatment of symptomatic uterine fibroids.

PubMed

Galen, Donald I

2015-10-15

Uterine fibroids occur singly or as multiple benign tumors originating in the myometrium. Because they vary in size and location, the approach and technique for their identification and surgical management vary. Reference images, such as ultrasound images, magnetic resonance images, and sonohystograms, do not provide real-time intraoperative findings. Electromagnetic image guidance, as incorporated in the Acessa Guidance System, has been cleared by the FDA to facilitate targeting and ablation of uterine fibroids during laparoscopic surgery. This is the first feasibility study to verify the features and usefulness of the guidance system in targeting symptomatic uterine fibroids-particularly hard-to-reach intramural fibroids and those abutting the endometrium. One gynecologic surgeon, who had extensive prior experience in laparoscopic ultrasound-guided identification of fibroids, treated five women with symptomatic uterine fibroids using the Acessa Guidance System. The surgeon evaluated the system and its features in terms of responses to prescribed statements; the responses were analyzed prospectively. The surgeon strongly agreed (96 %) or agreed (4 %) with statements describing the helpfulness of the transducer and handpiece's dynamic animation in targeting each fibroid, reaching the fibroid quickly, visualizing the positions of the transducer and handpiece within the pelvic cavity, and providing the surgeon with confidence when targeting the fibroid even during "out-of-plane" positioning of the handpiece. The surgeon's positive user experience was evident in the guidance system's facilitation of accurate handpiece tip placement during targeting and ablation of uterine fibroids. Continued study of electromagnetic image guidance in the laparoscopic identification and treatment of fibroids is warranted. ClinicalTrials.gov Identifier: NCT01842789.

Space-based infrared sensors of space target imaging effect analysis

NASA Astrophysics Data System (ADS)

Dai, Huayu; Zhang, Yasheng; Zhou, Haijun; Zhao, Shuang

2018-02-01

Target identification problem is one of the core problem of ballistic missile defense system, infrared imaging simulation is an important means of target detection and recognition. This paper first established the space-based infrared sensors ballistic target imaging model of point source on the planet's atmosphere; then from two aspects of space-based sensors camera parameters and target characteristics simulated atmosphere ballistic target of infrared imaging effect, analyzed the camera line of sight jitter, camera system noise and different imaging effects of wave on the target.

Intelligent person identification system using stereo camera-based height and stride estimation

NASA Astrophysics Data System (ADS)

Ko, Jung-Hwan; Jang, Jae-Hun; Kim, Eun-Soo

2005-05-01

In this paper, a stereo camera-based intelligent person identification system is suggested. In the proposed method, face area of the moving target person is extracted from the left image of the input steros image pair by using a threshold value of YCbCr color model and by carrying out correlation between the face area segmented from this threshold value of YCbCr color model and the right input image, the location coordinates of the target face can be acquired, and then these values are used to control the pan/tilt system through the modified PID-based recursive controller. Also, by using the geometric parameters between the target face and the stereo camera system, the vertical distance between the target and stereo camera system can be calculated through a triangulation method. Using this calculated vertical distance and the angles of the pan and tilt, the target's real position data in the world space can be acquired and from them its height and stride values can be finally extracted. Some experiments with video images for 16 moving persons show that a person could be identified with these extracted height and stride parameters.

Department of Defense Chemical and Biological Defense Program. FY2004-2006 Performance Plan

DTIC Science & Technology

2005-03-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to identify...Range Biometric Target ID System Explore technologies for a long range biometric target identification system. Air Containment Monitoring System...Continue development of systems for contained air monitoring for chemical agents.Long Range Biometric Air Containment Monitoring System Continued

Department of Defense Chemical, Biological, Radiological, and Nuclear Defense Program. FY2003-2005 Performance Plan

DTIC Science & Technology

2004-05-01

Agents (NTAs) Compare the direct effects of PAF on smooth muscle, hematic constituents, and lung to determine role in toxicity. Continue to...baselined. Long Range Biometric Target ID System Explore technologies for a long range biometric target identification system. 3.5.1.6

Detection and identification of human targets in radar data

NASA Astrophysics Data System (ADS)

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.

Detection, recognition, identification, and tracking of military vehicles using biomimetic intelligence

NASA Astrophysics Data System (ADS)

Pace, Paul W.; Sutherland, John

2001-10-01

This project is aimed at analyzing EO/IR images to provide automatic target detection/recognition/identification (ATR/D/I) of militarily relevant land targets. An increase in performance was accomplished using a biomimetic intelligence system functioning on low-cost, commercially available processing chips. Biomimetic intelligence has demonstrated advanced capabilities in the areas of hand- printed character recognition, real-time detection/identification of multiple faces in full 3D perspectives in cluttered environments, advanced capabilities in classification of ground-based military vehicles from SAR, and real-time ATR/D/I of ground-based military vehicles from EO/IR/HRR data in cluttered environments. The investigation applied these tools to real data sets and examined the parameters such as the minimum resolution for target recognition, the effect of target size, rotation, line-of-sight changes, contrast, partial obscuring, background clutter etc. The results demonstrated a real-time ATR/D/I capability against a subset of militarily relevant land targets operating in a realistic scenario. Typical results on the initial EO/IR data indicate probabilities of correct classification of resolved targets to be greater than 95 percent.

Identification of ground targets from airborne platforms

NASA Astrophysics Data System (ADS)

Doe, Josh; Boettcher, Evelyn; Miller, Brian

2009-05-01

The US Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate (NVESD) sensor performance models predict the ability of soldiers to perform a specified military discrimination task using an EO/IR sensor system. Increasingly EO/IR systems are being used on manned and un-manned aircraft for surveillance and target acquisition tasks. In response to this emerging requirement, the NVESD Modeling and Simulation division has been tasked to compare target identification performance between ground-to-ground and air-to-ground platforms for both IR and visible spectra for a set of wheeled utility vehicles. To measure performance, several forced choice experiments were designed and administered and the results analyzed. This paper describes these experiments and reports the results as well as the NVTherm model calibration factors derived for the infrared imagery.

Identification of handheld objects for electro-optic/FLIR applications

NASA Astrophysics Data System (ADS)

Moyer, Steve K.; Flug, Eric; Edwards, Timothy C.; Krapels, Keith A.; Scarbrough, John

2004-08-01

This paper describes research on the determination of the fifty-percent probability of identification cycle criterion (N50) for two sets of handheld objects. The first set consists of 12 objects which are commonly held in a single hand. The second set consists of 10 objects commonly held in both hands. These sets consist of not only typical civilian handheld objects but also objects that are potentially lethal. A pistol, a cell phone, a rocket propelled grenade (RPG) launcher, and a broom are examples of the objects in these sets. The discrimination of these objects is an inherent part of homeland security, force protection, and also general population security. Objects were imaged from each set in the visible and mid-wave infrared (MWIR) spectrum. Various levels of blur are then applied to these images. These blurred images were then used in a forced choice perception experiment. Results were analyzed as a function of blur level and target size to give identification probability as a function of resolvable cycles on target. These results are applicable to handheld object target acquisition estimates for visible imaging systems and MWIR systems. This research provides guidance in the design and analysis of electro-optical systems and forward-looking infrared (FLIR) systems for use in homeland security, force protection, and also general population security.

Multiple-target tracking implementation in the ebCMOS camera system: the LUSIPHER prototype

NASA Astrophysics Data System (ADS)

Doan, Quang Tuyen; Barbier, Remi; Dominjon, Agnes; Cajgfinger, Thomas; Guerin, Cyrille

2012-06-01

The domain of the low light imaging systems progresses very fast, thanks to detection and electronic multiplication technology evolution, such as the emCCD (electron multiplying CCD) or the ebCMOS (electron bombarded CMOS). We present an ebCMOS camera system that is able to track every 2 ms more than 2000 targets with a mean number of photons per target lower than two. The point light sources (targets) are spots generated by a microlens array (Shack-Hartmann) used in adaptive optics. The Multiple-Target-Tracking designed and implemented on a rugged workstation is described. The results and the performances of the system on the identification and tracking are presented and discussed.

Assigning unique identification numbers to new user accounts and groups in a computing environment with multiple registries

DOEpatents

DeRobertis, Christopher V.; Lu, Yantian T.

2010-02-23

A method, system, and program storage device for creating a new user account or user group with a unique identification number in a computing environment having multiple user registries is provided. In response to receiving a command to create a new user account or user group, an operating system of a clustered computing environment automatically checks multiple registries configured for the operating system to determine whether a candidate identification number for the new user account or user group has been assigned already to one or more existing user accounts or groups, respectively. The operating system automatically assigns the candidate identification number to the new user account or user group created in a target user registry if the checking indicates that the candidate identification number has not been assigned already to any of the existing user accounts or user groups, respectively.

EOID Evaluation and Automated Target Recognition

DTIC Science & Technology

2002-09-30

Electro - Optic IDentification (EOID) sensors into shallow water littoral zone minehunting systems on towed, remotely operated, and autonomous platforms. These downlooking laser-based sensors operate at unparalleled standoff ranges in visible wavelengths to image and identify mine-like objects (MLOs) that have been detected through other sensing means such as magnetic induction and various modes of acoustic imaging. Our long term goal is to provide a robust automated target cueing and identification capability for use with these imaging sensors. It is also our goal to assist

EOID Evaluation and Automated Target Recognition

DTIC Science & Technology

2001-09-30

Electro - Optic IDentification (EOID) sensors into shallow water littoral zone minehunting systems on towed, remotely operated, and autonomous platforms. These downlooking laser-based sensors operate at unparalleled standoff ranges in visible wavelengths to image and identify mine-like objects that have been detected through other sensing means such as magnetic induction and various modes of acoustic imaging. Our long term goal is to provide a robust automated target cueing and identification capability for use with these imaging sensors. It is also our goal to assist the

Quantitative and Systems Pharmacology. 1. In Silico Prediction of Drug-Target Interactions of Natural Products Enables New Targeted Cancer Therapy.

PubMed

Fang, Jiansong; Wu, Zengrui; Cai, Chuipu; Wang, Qi; Tang, Yun; Cheng, Feixiong

2017-11-27

Natural products with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for natural products at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we proposed a systems pharmacology infrastructure to predict new drug targets and anticancer indications of natural products. Specifically, we reconstructed a global drug-target network with 7,314 interactions connecting 751 targets and 2,388 natural products and built predictive network models via a balanced substructure-drug-target network-based inference approach. A high area under receiver operating characteristic curve of 0.96 was yielded for predicting new targets of natural products during cross-validation. The newly predicted targets of natural products (e.g., resveratrol, genistein, and kaempferol) with high scores were validated by various literature studies. We further built the statistical network models for identification of new anticancer indications of natural products through integration of both experimentally validated and computationally predicted drug-target interactions of natural products with known cancer proteins. We showed that the significantly predicted anticancer indications of multiple natural products (e.g., naringenin, disulfiram, and metformin) with new mechanism-of-action were validated by various published experimental evidence. In summary, this study offers powerful computational systems pharmacology approaches and tools for the development of novel targeted cancer therapies by exploiting the polypharmacology of natural products.

A high-throughput screening system targeting the nuclear export pathway via the third nuclear export signal of influenza A virus nucleoprotein.

PubMed

Kakisaka, Michinori; Mano, Takafumi; Aida, Yoko

2016-06-02

Two classes of antiviral drugs, M2 channel inhibitors and neuraminidase (NA) inhibitors, are currently approved for the treatment of influenza; however, the development of resistance against these agents limits their efficacy. Therefore, the identification of new targets and the development of new antiviral drugs against influenza are urgently needed. The third nuclear export signal (NES3) of nucleoprotein (NP) is the most important for viral replication among seven NESs encoded by four viral proteins, NP, M1, NS1, and NS2. NP-NES3 is critical for the nuclear export of NP, and targeting NP-NES3 is therefore a promising strategy that may lead to the development of antiviral drugs. However, a high-throughput screening (HTS) system to identify inhibitors of NP nuclear export has not been established. Here, we developed a novel HTS system to evaluate the inhibitory effects of compounds on the nuclear export pathway mediated by NP-NES3 using a MDCK cell line stably expressing NP-NES3 fused to a green fluorescent protein from aequorea coerulescens (AcGFP-NP-NES3) and a cell imaging analyzer. This HTS system was used to screen a 9600-compound library, leading to the identification of several hit compounds with inhibitory activity against the nuclear export of AcGFP-NP-NES3. The present HTS system provides a useful strategy for the identification of inhibitors targeting the nuclear export of NP via its NES3 sequence. Copyright © 2016. Published by Elsevier B.V.

Large-Scale Chemical Similarity Networks for Target Profiling of Compounds Identified in Cell-Based Chemical Screens

PubMed Central

Lo, Yu-Chen; Senese, Silvia; Li, Chien-Ming; Hu, Qiyang; Huang, Yong; Damoiseaux, Robert; Torres, Jorge Z.

2015-01-01

Target identification is one of the most critical steps following cell-based phenotypic chemical screens aimed at identifying compounds with potential uses in cell biology and for developing novel disease therapies. Current in silico target identification methods, including chemical similarity database searches, are limited to single or sequential ligand analysis that have limited capabilities for accurate deconvolution of a large number of compounds with diverse chemical structures. Here, we present CSNAP (Chemical Similarity Network Analysis Pulldown), a new computational target identification method that utilizes chemical similarity networks for large-scale chemotype (consensus chemical pattern) recognition and drug target profiling. Our benchmark study showed that CSNAP can achieve an overall higher accuracy (>80%) of target prediction with respect to representative chemotypes in large (>200) compound sets, in comparison to the SEA approach (60–70%). Additionally, CSNAP is capable of integrating with biological knowledge-based databases (Uniprot, GO) and high-throughput biology platforms (proteomic, genetic, etc) for system-wise drug target validation. To demonstrate the utility of the CSNAP approach, we combined CSNAP's target prediction with experimental ligand evaluation to identify the major mitotic targets of hit compounds from a cell-based chemical screen and we highlight novel compounds targeting microtubules, an important cancer therapeutic target. The CSNAP method is freely available and can be accessed from the CSNAP web server (http://services.mbi.ucla.edu/CSNAP/). PMID:25826798

BP network identification technology of infrared polarization based on fuzzy c-means clustering

NASA Astrophysics Data System (ADS)

Zeng, Haifang; Gu, Guohua; He, Weiji; Chen, Qian; Yang, Wei

2011-08-01

Infrared detection system is frequently employed on surveillance operations and reconnaissance mission to detect particular targets of interest in both civilian and military communities. By incorporating the polarization of light as supplementary information, the target discrimination performance could be enhanced. So this paper proposed an infrared target identification method which is based on fuzzy theory and neural network with polarization properties of targets. The paper utilizes polarization degree and light intensity to advance the unsupervised KFCM (kernel fuzzy C-Means) clustering method. And establish different material pol1arization properties database. In the built network, the system can feedback output corresponding material types of probability distribution toward any input polarized degree such as 10° 15°, 20°, 25°, 30°. KFCM, which has stronger robustness and accuracy than FCM, introduces kernel idea and gives the noise points and invalid value different but intuitively reasonable weights. Because of differences in characterization of material properties, there will be some conflicts in classification results. And D - S evidence theory was used in the combination of the polarization and intensity information. Related results show KFCM clustering precision and operation rate are higher than that of the FCM clustering method. The artificial neural network method realizes material identification, which reasonable solved the problems of complexity in environmental information of infrared polarization, and improperness of background knowledge and inference rule. This method of polarization identification is fast in speed, good in self-adaption and high in resolution.

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

PubMed

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.

A high-speed BCI based on code modulation VEP

NASA Astrophysics Data System (ADS)

Bin, Guangyu; Gao, Xiaorong; Wang, Yijun; Li, Yun; Hong, Bo; Gao, Shangkai

2011-04-01

Recently, electroencephalogram-based brain-computer interfaces (BCIs) have attracted much attention in the fields of neural engineering and rehabilitation due to their noninvasiveness. However, the low communication speed of current BCI systems greatly limits their practical application. In this paper, we present a high-speed BCI based on code modulation of visual evoked potentials (c-VEP). Thirty-two target stimuli were modulated by a time-shifted binary pseudorandom sequence. A multichannel identification method based on canonical correlation analysis (CCA) was used for target identification. The online system achieved an average information transfer rate (ITR) of 108 ± 12 bits min-1 on five subjects with a maximum ITR of 123 bits min-1 for a single subject.

A comparison of machine learning techniques for detection of drug target articles.

PubMed

Danger, Roxana; Segura-Bedmar, Isabel; Martínez, Paloma; Rosso, Paolo

2010-12-01

Important progress in treating diseases has been possible thanks to the identification of drug targets. Drug targets are the molecular structures whose abnormal activity, associated to a disease, can be modified by drugs, improving the health of patients. Pharmaceutical industry needs to give priority to their identification and validation in order to reduce the long and costly drug development times. In the last two decades, our knowledge about drugs, their mechanisms of action and drug targets has rapidly increased. Nevertheless, most of this knowledge is hidden in millions of medical articles and textbooks. Extracting knowledge from this large amount of unstructured information is a laborious job, even for human experts. Drug target articles identification, a crucial first step toward the automatic extraction of information from texts, constitutes the aim of this paper. A comparison of several machine learning techniques has been performed in order to obtain a satisfactory classifier for detecting drug target articles using semantic information from biomedical resources such as the Unified Medical Language System. The best result has been achieved by a Fuzzy Lattice Reasoning classifier, which reaches 98% of ROC area measure. Copyright © 2010 Elsevier Inc. All rights reserved.

Utilization of volume correlation filters for underwater mine identification in LIDAR imagery

NASA Astrophysics Data System (ADS)

Walls, Bradley

2008-04-01

Underwater mine identification persists as a critical technology pursued aggressively by the Navy for fleet protection. As such, new and improved techniques must continue to be developed in order to provide measurable increases in mine identification performance and noticeable reductions in false alarm rates. In this paper we show how recent advances in the Volume Correlation Filter (VCF) developed for ground based LIDAR systems can be adapted to identify targets in underwater LIDAR imagery. Current automated target recognition (ATR) algorithms for underwater mine identification employ spatial based three-dimensional (3D) shape fitting of models to LIDAR data to identify common mine shapes consisting of the box, cylinder, hemisphere, truncated cone, wedge, and annulus. VCFs provide a promising alternative to these spatial techniques by correlating 3D models against the 3D rendered LIDAR data.

UAV-borne X-band radar for MAV collision avoidance

NASA Astrophysics Data System (ADS)

Moses, Allistair A.; Rutherford, Matthew J.; Kontitsis, Michail; Valavanis, Kimon P.

2011-05-01

Increased use of Miniature (Unmanned) Aerial Vehicles (MAVs) is coincidentally accompanied by a notable lack of sensors suitable for enabling further increases in levels of autonomy and consequently, integration into the National Airspace System (NAS). The majority of available sensors suitable for MAV integration are based on infrared detectors, focal plane arrays, optical and ultrasonic rangefinders, etc. These sensors are generally not able to detect or identify other MAV-sized targets and, when detection is possible, considerable computational power is typically required for successful identification. Furthermore, performance of visual-range optical sensor systems can suffer greatly when operating in the conditions that are typically encountered during search and rescue, surveillance, combat, and most common MAV applications. However, the addition of a miniature radar system can, in consort with other sensors, provide comprehensive target detection and identification capabilities for MAVs. This trend is observed in manned aviation where radar systems are the primary detection and identification sensor system. Within this document a miniature, lightweight X-Band radar system for use on a miniature (710mm rotor diameter) rotorcraft is described. We present analyses of the performance of the system in a realistic scenario with two MAVs. Additionally, an analysis of MAV navigation and collision avoidance behaviors is performed to determine the effect of integrating radar systems into MAV-class vehicles.

Modeling and performance of HF/OTH (High-Frequency/Over-the-Horizon) radar target identification systems

NASA Astrophysics Data System (ADS)

Strausberger, Donald J.

Several Radar Target Identification (RTI) techniques have been developed at The Ohio State University in recent years. Using the ElectroScience Laboratory compact range a large database of coherent RCS measurement has been constructed for several types of targets (aircraft, ships, and ground vehicles) at a variety of polarizations, aspect angles, and frequency bands. This extensive database has been used to analyze the performance of several different classification algorithms through the use of computer simulations. In order to optimize classification performance, it was concluded that the radar frequency range should lie in the Rayleigh-resonance frequency range, where the wavelength is on the order of or larger than the target size. For aircraft and ships with general dimensions on the order of 10 meters to 100 meters it is apparent that the High Frequency (HF) band provides optimal classification performance. Since existing HF radars are currently being used for detection and tracking or aircraft and ships of these dimensions, it is natural to further investigate the possibility of using these existing radars as the measurement devices in a radar target classification system.

Bullet Trap Feasibility Assessment and Implementation Plan. (Technology Identification).

DTIC Science & Technology

1996-03-01

reduce costs, perhaps one of their premier assets is income generation . Projectiles fired into and recovered from TEC System products can be resold...ombat shooting scenarios with up to 15 individual targets as far away as 300 yards. Page 7 \\IEUMATIC TARGET SYSTEMS gt reliable . portable and... SYYSTEM ] 3DULAR BALLISTIC PANELS (MBPs) A~rking with recycled rubber tire products, DUE- RON has created the proprietary MBP System ,or use in the

Image change detection systems, methods, and articles of manufacture

DOEpatents

Jones, James L.; Lassahn, Gordon D.; Lancaster, Gregory D.

2010-01-05

Aspects of the invention relate to image change detection systems, methods, and articles of manufacture. According to one aspect, a method of identifying differences between a plurality of images is described. The method includes loading a source image and a target image into memory of a computer, constructing source and target edge images from the source and target images to enable processing of multiband images, displaying the source and target images on a display device of the computer, aligning the source and target edge images, switching displaying of the source image and the target image on the display device, to enable identification of differences between the source image and the target image.

Classification of Non-Time-Locked Rapid Serial Visual Presentation Events for Brain-Computer Interaction Using Deep Learning

DTIC Science & Technology

2014-07-08

internction ( BCI ) system allows h uman subjects to communicate with or control an extemal device with their brain signals [1], or to use those brain...signals to interact with computers, environments, or even other humans [2]. One application of BCI is to use brnin signals to distinguish target...images within a large collection of non-target images [2]. Such BCI -based systems can drastically increase the speed of target identification in

ManPortable and UGV LIVAR: advances in sensor suite integration bring improvements to target observation and identification for the electronic battlefield

NASA Astrophysics Data System (ADS)

Lynam, Jeff R.

2001-09-01

A more highly integrated, electro-optical sensor suite using Laser Illuminated Viewing and Ranging (LIVAR) techniques is being developed under the Army Advanced Concept Technology- II (ACT-II) program for enhanced manportable target surveillance and identification. The ManPortable LIVAR system currently in development employs a wide-array of sensor technologies that provides the foot-bound soldier and UGV significant advantages and capabilities in lightweight, fieldable, target location, ranging and imaging systems. The unit incorporates a wide field-of-view, 5DEG x 3DEG, uncooled LWIR passive sensor for primary target location. Laser range finding and active illumination is done with a triggered, flash-lamp pumped, eyesafe micro-laser operating in the 1.5 micron region, and is used in conjunction with a range-gated, electron-bombarded CCD digital camera to then image the target objective in a more- narrow, 0.3$DEG, field-of-view. Target range determination is acquired using the integrated LRF and a target position is calculated using data from other onboard devices providing GPS coordinates, tilt, bank and corrected magnetic azimuth. Range gate timing and coordinated receiver optics focus control allow for target imaging operations to be optimized. The onboard control electronics provide power efficient, system operations for extended field use periods from the internal, rechargeable battery packs. Image data storage, transmission, and processing performance capabilities are also being incorporated to provide the best all-around support, for the electronic battlefield, in this type of system. The paper will describe flash laser illumination technology, EBCCD camera technology with flash laser detection system, and image resolution improvement through frame averaging.

Passive IFF: Autonomous Nonintrusive Rapid Identification of Friendly Assets

NASA Technical Reports Server (NTRS)

Moynihan, Philip; Steenburg, Robert Van; Chao, Tien-Hsin

2004-01-01

A proposed optoelectronic instrument would identify targets rapidly, without need to radiate an interrogating signal, apply identifying marks to the targets, or equip the targets with transponders. The instrument was conceived as an identification, friend or foe (IFF) system in a battlefield setting, where it would be part of a targeting system for weapons, by providing rapid identification for aimed weapons to help in deciding whether and when to trigger them. The instrument could also be adapted to law-enforcement and industrial applications in which it is necessary to rapidly identify objects in view. The instrument would comprise mainly an optical correlator and a neural processor (see figure). The inherent parallel-processing speed and capability of the optical correlator would be exploited to obtain rapid identification of a set of probable targets within a scene of interest and to define regions within the scene for the neural processor to analyze. The neural processor would then concentrate on each region selected by the optical correlator in an effort to identify the target. Depending on whether or not a target was recognized by comparison of its image data with data in an internal database on which the neural processor was trained, the processor would generate an identifying signal (typically, friend or foe ). The time taken for this identification process would be less than the time needed by a human or robotic gunner to acquire a view of, and aim at, a target. An optical correlator that has been under development for several years and that has been demonstrated to be capable of tracking a cruise missile might be considered a prototype of the optical correlator in the proposed IFF instrument. This optical correlator features a 512-by-512-pixel input image frame and operates at an input frame rate of 60 Hz. It includes a spatial light modulator (SLM) for video-to-optical image conversion, a pair of precise lenses to effect Fourier transforms, a filter SLM for digital-to-optical correlation-filter data conversion, and a charge-coupled device (CCD) for detection of correlation peaks. In operation, the input scene grabbed by a video sensor is streamed into the input SLM. Precomputed correlation-filter data files representative of known targets are then downloaded and sequenced into the filter SLM at a rate of 1,000 Hz. When there occurs a match between the input target data and one of the known-target data files, the CCD detects a correlation peak at the location of the target. Distortion- invariant correlation filters from a bank of such filters are then sequenced through the optical correlator for each input frame. The net result is the rapid preliminary recognition of one or a few targets.

Identification of neuronal target genes for CCAAT/Enhancer Binding Proteins

PubMed Central

Kfoury, N.; Kapatos, G.

2009-01-01

CCAAT/Enhancer Binding Proteins (C/EBPs) play pivotal roles in development and plasticity of the nervous system. Identification of the physiological targets of C/EBPs (C/EBP target genes) should therefore provide insight into the underlying biology of these processes. We used unbiased genome-wide mapping to identify 115 C/EBPβ target genes in PC12 cells that include transcription factors, neurotransmitter receptors, ion channels, protein kinases and synaptic vesicle proteins. C/EBPβ binding sites were located primarily within introns, suggesting novel regulatory functions, and were associated with binding sites for other developmentally important transcription factors. Experiments using dominant negatives showed C/EBPβ to repress transcription of a subset of target genes. Target genes in rat brain were subsequently found to preferentially bind C/EBPα, β and δ. Analysis of the hippocampal transcriptome of C/EBPβ knockout mice revealed dysregulation of a high percentage of transcripts identified as C/EBP target genes. These results support the hypothesis that C/EBPs play non-redundant roles in the brain. PMID:19103292

Discovery of novel drug targets and their functions using phenotypic screening of natural products.

PubMed

Chang, Junghwa; Kwon, Ho Jeong

2016-03-01

Natural products are valuable resources that provide a variety of bioactive compounds and natural pharmacophores in modern drug discovery. Discovery of biologically active natural products and unraveling their target proteins to understand their mode of action have always been critical hurdles for their development into clinical drugs. For effective discovery and development of bioactive natural products into novel therapeutic drugs, comprehensive screening and identification of target proteins are indispensable. In this review, a systematic approach to understanding the mode of action of natural products isolated using phenotypic screening involving chemical proteomics-based target identification is introduced. This review highlights three natural products recently discovered via phenotypic screening, namely glucopiericidin A, ecumicin, and terpestacin, as representative case studies to revisit the pivotal role of natural products as powerful tools in discovering the novel functions and druggability of targets in biological systems and pathological diseases of interest.

Radar image processing of real aperture SLAR data for the detection and identification of iceberg and ship targets

NASA Technical Reports Server (NTRS)

Marthaler, J. G.; Heighway, J. E.

1979-01-01

An iceberg detection and identification system consisting of a moderate resolution Side Looking Airborne Radar (SLAR) interfaced with a Radar Image Processor (RIP) based on a ROLM 1664 computer with a 32K core memory updatable to 64K is described. The system can be operated in high- or low-resolution sampling modes. Specifically designed algorithms are applied to digitized signal returns to provide automatic target detection and location, geometrically correct video image display and data recording. The real aperture Motorola AN/APS-94D SLAR operates in the X-band and is tunable between 9.10 and 9.40 GHz; its output power is 45 kW peak with a pulse repetition rate of 750 pulses per hour. Schematic diagrams of the system are provided, together with preliminary test data.

The Confidence-Accuracy Relationship in Eyewitness Identification: Effects of Lineup Instructions, Foil Similarity, and Target-Absent Base Rates

ERIC Educational Resources Information Center

Brewer, Neil; Wells, Gary L.

2006-01-01

Discriminating accurate from mistaken eyewitness identifications is a major issue facing criminal justice systems. This study examined whether eyewitness confidence assists such decisions under a variety of conditions using a confidence-accuracy (CA) calibration approach. Participants (N = 1,200) viewed a simulated crime and attempted 2 separate…

21 CFR 884.6200 - Assisted reproduction laser system.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Assisted reproduction laser system. 884.6200... Assisted reproduction laser system. (a) Identification. The assisted reproduction laser system is a device that images, targets, and controls the power and pulse duration of a laser beam used to ablate a small...

21 CFR 884.6200 - Assisted reproduction laser system.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Assisted reproduction laser system. 884.6200... Assisted reproduction laser system. (a) Identification. The assisted reproduction laser system is a device that images, targets, and controls the power and pulse duration of a laser beam used to ablate a small...

21 CFR 884.6200 - Assisted reproduction laser system.

Code of Federal Regulations, 2012 CFR

2012-04-01

... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Assisted reproduction laser system. 884.6200... Assisted reproduction laser system. (a) Identification. The assisted reproduction laser system is a device that images, targets, and controls the power and pulse duration of a laser beam used to ablate a small...

21 CFR 884.6200 - Assisted reproduction laser system.

Code of Federal Regulations, 2014 CFR

2014-04-01

... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Assisted reproduction laser system. 884.6200... Assisted reproduction laser system. (a) Identification. The assisted reproduction laser system is a device that images, targets, and controls the power and pulse duration of a laser beam used to ablate a small...

21 CFR 884.6200 - Assisted reproduction laser system.

Code of Federal Regulations, 2013 CFR

2013-04-01

... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Assisted reproduction laser system. 884.6200... Assisted reproduction laser system. (a) Identification. The assisted reproduction laser system is a device that images, targets, and controls the power and pulse duration of a laser beam used to ablate a small...

Lineup identification by children: effects of clothing bias.

PubMed

Freire, Alejo; Lee, Kang; Williamson, Karen S; Stuart, Sarah J E; Lindsay, R C L

2004-06-01

This study examined effects of clothing cues on children's identification accuracy from lineups. Four- to 14-year-olds (n = 228) saw 12 video clips of individuals, each wearing a distinctly colored shirt. After watching each clip children were presented with a target-present or target-absent photo lineup. Three clothing conditions were included. In 2 conditions all lineup members wore the same colored shirt; in the third, biased condition, the shirt color of only one individual matched that seen in the preceding clip (the target in target-present trials and the replacement in target-absent trials). Correct identifications of the target in target-present trials were most frequent in the biased condition, whereas in target-absent trials the biased condition led to more false identifications of the target replacement. Older children were more accurate than younger children, both in choosing the target from target-present lineups and rejecting target-absent lineups. These findings suggest that a simple clothing cue such as shirt color can have a significant impact on children's lineup identification accuracy.

Lineup Identification by Children: Effects of Clothing Bias

PubMed Central

Freire, Alejo; Lee, Kang; Williamson, Karen S.; Stuart, Sarah J. E.; Lindsay, R. C. L.

2008-01-01

This study examined effects of clothing cues on children's identification accuracy from lineups. Four- to 14-year-olds (n = 228) saw 12 video clips of individuals, each wearing a distinctly colored shirt. After watching each clip children were presented with a target-present or target-absent photo lineup. Three clothing conditions were included. In 2 conditions all lineup members wore the same colored shirt; in the third, biased condition, the shirt color of only one individual matched that seen in the preceding clip (the target in target-present trials and the replacement in target-absent trials). Correct identifications of the target in target-present trials were most frequent in the biased condition, whereas in target-absent trials the biased condition led to more false identifications of the target replacement. Older children were more accurate than younger children, both in choosing the target from target-present lineups and rejecting target-absent lineups. These findings suggest that a simple clothing cue such as shirt color can have a significant impact on children's lineup identification accuracy. PMID:15264450

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

NASA Astrophysics Data System (ADS)

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.

Identification of glia phenotype modulators based on select glial function regulatory signaling pathways.

PubMed

Lee, Sun-Hwa; Suk, Kyoungho

2018-04-20

Despite the considerable social and economic burden on the healthcare system worldwide due to neurodegenerative diseases, there are currently few disease-altering treatment options for many of these conditions. Therefore, new approaches for both prevention and intervention for neurodegenerative diseases are urgently required. Microglia-mediated neurotoxicity is one of the pathologic hallmarks common to Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis. Current therapeutic approaches to target microglia-mediated neurotoxicity are focused on the identification of glia phenotype modulators (GPMs), which can inhibit the 'classical' pro-inflammatory and neurotoxic phenotypes of microglia. Areas covered: This article reviews selected microglial molecular targets and pathways involved in either neurotoxicity or neuroprotection and how their identification. Expert opinion: Microglial activation and their signaling pathways have important implications in the neurotoxicity and brain disorders. Pharmacological modulation of microglial activation may serve as a potential therapeutic approach for targeting microglia-mediated neurotoxicity. However, given that microglia change their activation states depending on the timing, stage, and severity of disease, and even aging, the appropriate window should be considered for this approach to be clinically effective. In the future, the identification of unknown extracellular signals and intracellular molecular switches that control phenotypic shifts may facilitate the development of novel therapeutics targeting microglia-mediated neurotoxicity.

Neuronal Target Identification Requires AHA-1-Mediated Fine-Tuning of Wnt Signaling in C. elegans

PubMed Central

Zhang, Jingyan; Li, Xia; Jevince, Angela R.; Guan, Liying; Wang, Jiaming; Hall, David H.; Huang, Xun; Ding, Mei

2013-01-01

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. PMID:23825972

OPTICAL correlation identification technology applied in underwater laser imaging target identification

NASA Astrophysics Data System (ADS)

Yao, Guang-tao; Zhang, Xiao-hui; Ge, Wei-long

2012-01-01

The underwater laser imaging detection is an effective method of detecting short distance target underwater as an important complement of sonar detection. With the development of underwater laser imaging technology and underwater vehicle technology, the underwater automatic target identification has gotten more and more attention, and is a research difficulty in the area of underwater optical imaging information processing. Today, underwater automatic target identification based on optical imaging is usually realized with the method of digital circuit software programming. The algorithm realization and control of this method is very flexible. However, the optical imaging information is 2D image even 3D image, the amount of imaging processing information is abundant, so the electronic hardware with pure digital algorithm will need long identification time and is hard to meet the demands of real-time identification. If adopt computer parallel processing, the identification speed can be improved, but it will increase complexity, size and power consumption. This paper attempts to apply optical correlation identification technology to realize underwater automatic target identification. The optics correlation identification technology utilizes the Fourier transform characteristic of Fourier lens which can accomplish Fourier transform of image information in the level of nanosecond, and optical space interconnection calculation has the features of parallel, high speed, large capacity and high resolution, combines the flexibility of calculation and control of digital circuit method to realize optoelectronic hybrid identification mode. We reduce theoretical formulation of correlation identification and analyze the principle of optical correlation identification, and write MATLAB simulation program. We adopt single frame image obtained in underwater range gating laser imaging to identify, and through identifying and locating the different positions of target, we can improve the speed and orientation efficiency of target identification effectively, and validate the feasibility of this method primarily.

Advancements in robust algorithm formulation for speaker identification of whispered speech

NASA Astrophysics Data System (ADS)

Fan, Xing

Whispered speech is an alternative speech production mode from neutral speech, which is used by talkers intentionally in natural conversational scenarios to protect privacy and to avoid certain content from being overheard/made public. Due to the profound differences between whispered and neutral speech in production mechanism and the absence of whispered adaptation data, the performance of speaker identification systems trained with neutral speech degrades significantly. This dissertation therefore focuses on developing a robust closed-set speaker recognition system for whispered speech by using no or limited whispered adaptation data from non-target speakers. This dissertation proposes the concept of "High''/"Low'' performance whispered data for the purpose of speaker identification. A variety of acoustic properties are identified that contribute to the quality of whispered data. An acoustic analysis is also conducted to compare the phoneme/speaker dependency of the differences between whispered and neutral data in the feature domain. The observations from those acoustic analysis are new in this area and also serve as a guidance for developing robust speaker identification systems for whispered speech. This dissertation further proposes two systems for speaker identification of whispered speech. One system focuses on front-end processing. A two-dimensional feature space is proposed to search for "Low''-quality performance based whispered utterances and separate feature mapping functions are applied to vowels and consonants respectively in order to retain the speaker's information shared between whispered and neutral speech. The other system focuses on speech-mode-independent model training. The proposed method generates pseudo whispered features from neutral features by using the statistical information contained in a whispered Universal Background model (UBM) trained from extra collected whispered data from non-target speakers. Four modeling methods are proposed for the transformation estimation in order to generate the pseudo whispered features. Both of the above two systems demonstrate a significant improvement over the baseline system on the evaluation data. This dissertation has therefore contributed to providing a scientific understanding of the differences between whispered and neutral speech as well as improved front-end processing and modeling method for speaker identification of whispered speech. Such advancements will ultimately contribute to improve the robustness of speech processing systems.

Non-Cooperative Air Target Identification Using Radar (l’Identification radar des cibles aeriennes non cooperatives)

DTIC Science & Technology

1998-11-01

are already operational in the radar domain , e.g. in airborne radars. NATO fighter aircraft are equipped with transponder systems answering on...Mise en forme et 6talonnage des donn6es SER moyenne pour un domaine de fr6quence (bande passante du code utilis6) et un secteur Ce module extrait les...cooperatives) Papers presented at the Symposium of the RTO Systems Concepts and Integration Panel (SCI) held in Mannheim, Germany, 22-24 April 1998. 1

Countering MANPADS: study of new concepts and applications

NASA Astrophysics Data System (ADS)

Maltese, Dominique; Robineau, Jacques; Audren, Jean-Thierry; Aragones, Julien; Sailliot, Christophe

2006-05-01

The latest events of ground-to-air Man Portable Air Defense (MANPAD) attacks against aircraft have revealed a new threat both for military and civilian aircraft. Consequently, the implementation of Protecting systems (i.e. Directed InfraRed Counter Measure - DIRCM) in order to face IR guided missiles turns out to be now inevitable. In a near future, aircraft will have to possess detection, tracking, targeting and jamming capabilities to face single and multiple MANPAD threats fired in short-range scenarios from various environments (urban sites, landscape...). In this paper, a practical example of a DIRCM system under study at SAGEM DEFENSE & SECURITY company is presented. The self-protection solution includes built-in and automatic locking-on, tracking, identification and laser jamming capabilities, including defeat assessment. Target Designations are provided by a Missile Warning System. Multiple Target scenarios have been considered to design the system architecture. The article deals with current and future threats (IR seekers of different generations...), scenarios and platforms for system definition. Plus, it stresses on self-protection solutions based on laser jamming capability. Different strategies including target identification, multi band laser, active imagery are described. The self-protection system under study at SAGEM DEFENSE & SECURITY company is also a part of this chapter. Eventually, results of self-protection scenarios are provided for different MANPAD scenarios. Data have been obtained from a simulation software. The results highlight how the system reacts to incoming IR-guided missiles in short time scenarios.

Identification of Target Complaints by Computer Interview: Evaluation of the Computerized Assessment System for Psychotherapy Evaluation and Research.

ERIC Educational Resources Information Center

Farrell, Albert D.; And Others

1987-01-01

Evaluated computer interview to standardize collection of target complaints. Adult outpatients (N=103) completed computer interview, unstructured intake interview, Symptoms Checklist-90, and Minnesota Multiphasic Personality Inventory. Results provided support for the computer interview in regard to reliability and validity though there was low…

Fusion of imaging and nonimaging data for surveillance aircraft

NASA Astrophysics Data System (ADS)

Shahbazian, Elisa; Gagnon, Langis; Duquet, Jean Remi; Macieszczak, Maciej; Valin, Pierre

1997-06-01

This paper describes a phased incremental integration approach for application of image analysis and data fusion technologies to provide automated intelligent target tracking and identification for airborne surveillance on board an Aurora Maritime Patrol Aircraft. The sensor suite of the Aurora consists of a radar, an identification friend or foe (IFF) system, an electronic support measures (ESM) system, a spotlight synthetic aperture radar (SSAR), a forward looking infra-red (FLIR) sensor and a link-11 tactical datalink system. Lockheed Martin Canada (LMCan) is developing a testbed, which will be used to analyze and evaluate approaches for combining the data provided by the existing sensors, which were initially not designed to feed a fusion system. Three concurrent research proof-of-concept activities provide techniques, algorithms and methodology into three sequential phases of integration of this testbed. These activities are: (1) analysis of the fusion architecture (track/contact/hybrid) most appropriate for the type of data available, (2) extraction and fusion of simple features from the imaging data into the fusion system performing automatic target identification, and (3) development of a unique software architecture which will permit integration and independent evolution, enhancement and optimization of various decision aid capabilities, such as multi-sensor data fusion (MSDF), situation and threat assessment (STA) and resource management (RM).

On the effectiveness of noise masks: naturalistic vs. un-naturalistic image statistics.

PubMed

Hansen, Bruce C; Hess, Robert F

2012-05-01

It has been argued that the human visual system is optimized for identification of broadband objects embedded in stimuli possessing orientation averaged power spectra fall-offs that obey the 1/f(β) relationship typically observed in natural scene imagery (i.e., β=2.0 on logarithmic axes). Here, we were interested in whether individual spatial channels leading to recognition are functionally optimized for narrowband targets when masked by noise possessing naturalistic image statistics (β=2.0). The current study therefore explores the impact of variable β noise masks on the identification of narrowband target stimuli ranging in spatial complexity, while simultaneously controlling for physical or perceived differences between the masks. The results show that β=2.0 noise masks produce the largest identification thresholds regardless of target complexity, and thus do not seem to yield functionally optimized channel processing. The differential masking effects are discussed in the context of contrast gain control. Copyright © 2012 Elsevier Ltd. All rights reserved.

The Yeast Saccharomyces cerevisiae: a versatile model system for the identification and characterization of bacterial virulence proteins.

PubMed

Siggers, Keri A; Lesser, Cammie F

2008-07-17

Microbial pathogens utilize complex secretion systems to deliver proteins into host cells. These effector proteins target and usurp host cell processes to promote infection and cause disease. While secretion systems are conserved, each pathogen delivers its own unique set of effectors. The identification and characterization of these effector proteins has been difficult, often limited by the lack of detectable signal sequences and functional redundancy. Model systems including yeast, worms, flies, and fish are being used to circumvent these issues. This technical review details the versatility and utility of yeast Saccharomyces cerevisiae as a system to identify and characterize bacterial effectors.

Network-assisted target identification for haploinsufficiency and homozygous profiling screens

PubMed Central

Wang, Sheng

2017-01-01

Chemical genomic screens have recently emerged as a systematic approach to drug discovery on a genome-wide scale. Drug target identification and elucidation of the mechanism of action (MoA) of hits from these noisy high-throughput screens remain difficult. Here, we present GIT (Genetic Interaction Network-Assisted Target Identification), a network analysis method for drug target identification in haploinsufficiency profiling (HIP) and homozygous profiling (HOP) screens. With the drug-induced phenotypic fitness defect of the deletion of a gene, GIT also incorporates the fitness defects of the gene’s neighbors in the genetic interaction network. On three genome-scale yeast chemical genomic screens, GIT substantially outperforms previous scoring methods on target identification on HIP and HOP assays, respectively. Finally, we showed that by combining HIP and HOP assays, GIT further boosts target identification and reveals potential drug’s mechanism of action. PMID:28574983

Optical/digital identification/verification system based on digital watermarking technology

NASA Astrophysics Data System (ADS)

Herrigel, Alexander; Voloshynovskiy, Sviatoslav V.; Hrytskiv, Zenon D.

2000-06-01

This paper presents a new approach for the secure integrity verification of driver licenses, passports or other analogue identification documents. The system embeds (detects) the reference number of the identification document with the DCT watermark technology in (from) the owner photo of the identification document holder. During verification the reference number is extracted and compared with the reference number printed in the identification document. The approach combines optical and digital image processing techniques. The detection system must be able to scan an analogue driver license or passport, convert the image of this document into a digital representation and then apply the watermark verification algorithm to check the payload of the embedded watermark. If the payload of the watermark is identical with the printed visual reference number of the issuer, the verification was successful and the passport or driver license has not been modified. This approach constitutes a new class of application for the watermark technology, which was originally targeted for the copyright protection of digital multimedia data. The presented approach substantially increases the security of the analogue identification documents applied in many European countries.

Analysis of A Drug Target-based Classification System using Molecular Descriptors.

PubMed

Lu, Jing; Zhang, Pin; Bi, Yi; Luo, Xiaomin

2016-01-01

Drug-target interaction is an important topic in drug discovery and drug repositioning. KEGG database offers a drug annotation and classification using a target-based classification system. In this study, we gave an investigation on five target-based classes: (I) G protein-coupled receptors; (II) Nuclear receptors; (III) Ion channels; (IV) Enzymes; (V) Pathogens, using molecular descriptors to represent each drug compound. Two popular feature selection methods, maximum relevance minimum redundancy and incremental feature selection, were adopted to extract the important descriptors. Meanwhile, an optimal prediction model based on nearest neighbor algorithm was constructed, which got the best result in identifying drug target-based classes. Finally, some key descriptors were discussed to uncover their important roles in the identification of drug-target classes.

Theory of Radar Target Discrimination

DTIC Science & Technology

1991-02-01

which a capability for target or system identification could be put to good use: air traffic control , border patrol, security and surveillance...different targets from each other, there would be big advantages in air safety. Airport traffic controllers have made serious errors from their...in a way that we can neither predict nor control . Of course, any data function d(t) which can be recorded for computer processing will be digitized and

A new comprehensive method for detection of livestock-related pathogenic viruses using a target enrichment system.

PubMed

Oba, Mami; Tsuchiaka, Shinobu; Omatsu, Tsutomu; Katayama, Yukie; Otomaru, Konosuke; Hirata, Teppei; Aoki, Hiroshi; Murata, Yoshiteru; Makino, Shinji; Nagai, Makoto; Mizutani, Tetsuya

2018-01-08

We tested usefulness of a target enrichment system SureSelect, a comprehensive viral nucleic acid detection method, for rapid identification of viral pathogens in feces samples of cattle, pigs and goats. This system enriches nucleic acids of target viruses in clinical/field samples by using a library of biotinylated RNAs with sequences complementary to the target viruses. The enriched nucleic acids are amplified by PCR and subjected to next generation sequencing to identify the target viruses. In many samples, SureSelect target enrichment method increased efficiencies for detection of the viruses listed in the biotinylated RNA library. Furthermore, this method enabled us to determine nearly full-length genome sequence of porcine parainfluenza virus 1 and greatly increased Breadth, a value indicating the ratio of the mapping consensus length in the reference genome, in pig samples. Our data showed usefulness of SureSelect target enrichment system for comprehensive analysis of genomic information of various viruses in field samples. Copyright © 2017 Elsevier Inc. All rights reserved.

Comprehensive predictions of target proteins based on protein-chemical interaction using virtual screening and experimental verifications.

PubMed

Kobayashi, Hiroki; Harada, Hiroko; Nakamura, Masaomi; Futamura, Yushi; Ito, Akihiro; Yoshida, Minoru; Iemura, Shun-Ichiro; Shin-Ya, Kazuo; Doi, Takayuki; Takahashi, Takashi; Natsume, Tohru; Imoto, Masaya; Sakakibara, Yasubumi

2012-04-05

Identification of the target proteins of bioactive compounds is critical for elucidating the mode of action; however, target identification has been difficult in general, mostly due to the low sensitivity of detection using affinity chromatography followed by CBB staining and MS/MS analysis. We applied our protocol of predicting target proteins combining in silico screening and experimental verification for incednine, which inhibits the anti-apoptotic function of Bcl-xL by an unknown mechanism. One hundred eighty-two target protein candidates were computationally predicted to bind to incednine by the statistical prediction method, and the predictions were verified by in vitro binding of incednine to seven proteins, whose expression can be confirmed in our cell system.As a result, 40% accuracy of the computational predictions was achieved successfully, and we newly found 3 incednine-binding proteins. This study revealed that our proposed protocol of predicting target protein combining in silico screening and experimental verification is useful, and provides new insight into a strategy for identifying target proteins of small molecules.

Comparison of conventional ultrasonography and ultrasonography-computed tomography fusion imaging for target identification using digital/real hybrid phantoms: a preliminary study.

PubMed

Soyama, Takeshi; Sakuhara, Yusuke; Kudo, Kohsuke; Abo, Daisuke; Wang, Jeff; Ito, Yoichi M; Hasegawa, Yu; Shirato, Hiroki

2016-07-01

This preliminary study compared ultrasonography-computed tomography (US-CT) fusion imaging and conventional ultrasonography (US) for accuracy and time required for target identification using a combination of real phantoms and sets of digitally modified computed tomography (CT) images (digital/real hybrid phantoms). In this randomized prospective study, 27 spheres visible on B-mode US were placed at depths of 3.5, 8.5, and 13.5 cm (nine spheres each). All 27 spheres were digitally erased from the CT images, and a radiopaque sphere was digitally placed at each of the 27 locations to create 27 different sets of CT images. Twenty clinicians were instructed to identify the sphere target using US alone and fusion imaging. The accuracy of target identification of the two methods was compared using McNemar's test. The mean time required for target identification and error distances were compared using paired t tests. At all three depths, target identification was more accurate and the mean time required for target identification was significantly less with US-CT fusion imaging than with US alone, and the mean error distances were also shorter with US-CT fusion imaging. US-CT fusion imaging was superior to US alone in terms of accurate and rapid identification of target lesions.

Nonenzymatic microorganism identification based on ribosomal RNA

NASA Astrophysics Data System (ADS)

Ives, Jeffrey T.; Pierini, Alicia M.; Stokes, Jeffrey A.; Wahlund, Thomas M.; Read, Betsy; Bechtel, James H.; Bronk, Burt V.

1999-11-01

Effective defense against biological warfare (BW) agents requires rapid, fieldable and accurate systems. For micro- organisms like bacteria and viruses, ribosomal RNA (rRNA) provides a valuable target with multiple advantages of species specificity and intrinsic target amplification. Vegetative and spore forms of bacteria contain approximately 104 copies of rRNA. Direct detection of rRNA copies can eliminate some of the interference and preparation difficulties involved in enzymatic amplification methods. In order to apply the advantages of rRNA to BW defense, we are developing a fieldable system based on 16S rRNA, physical disruption of the micro-organism, solid phase hybridization, and fluorescence detection. Our goals include species-specific identification, complete operation from raw sample to identification in 15 minutes or less, and compact, fieldable instrumentation. Initial work on this project has investigated the lysis and hybridization steps, the species-specificity of oligonucleotides probes, and the development of a novel electromagnetic method to physically disrupt the micro- organisms. Target bacteria have been Escherichia coli (E. coli) and Bacillus subtilis (B. subtilis). Continuing work includes further development of methods to rapidly disrupt the micro-organisms and release the rRNA, improved integration and processing, and extension to bacterial and mammalian viruses like MS2 and vesicular stomatitis virus.

Identification of secreted bacterial proteins by noncanonical amino acid tagging

PubMed Central

Mahdavi, Alborz; Szychowski, Janek; Ngo, John T.; Sweredoski, Michael J.; Graham, Robert L. J.; Hess, Sonja; Schneewind, Olaf; Mazmanian, Sarkis K.; Tirrell, David A.

2014-01-01

Pathogenic microbes have evolved complex secretion systems to deliver virulence factors into host cells. Identification of these factors is critical for understanding the infection process. We report a powerful and versatile approach to the selective labeling and identification of secreted pathogen proteins. Selective labeling of microbial proteins is accomplished via translational incorporation of azidonorleucine (Anl), a methionine surrogate that requires a mutant form of the methionyl-tRNA synthetase for activation. Secreted pathogen proteins containing Anl can be tagged by azide-alkyne cycloaddition and enriched by affinity purification. Application of the method to analysis of the type III secretion system of the human pathogen Yersinia enterocolitica enabled efficient identification of secreted proteins, identification of distinct secretion profiles for intracellular and extracellular bacteria, and determination of the order of substrate injection into host cells. This approach should be widely useful for the identification of virulence factors in microbial pathogens and the development of potential new targets for antimicrobial therapy. PMID:24347637

Emotional System for Military Target Identification

DTIC Science & Technology

2009-10-01

algorithm [23], and used it to solve a facial recognition problem. In other works [24,25], we explored the potential of using emotional neural...other application areas, such as security ( facial recognition ) and medical (blood cell identification), can be also efficiently used in military...Application of an emotional neural network to facial recognition . Neural Computing and Applications, 18(4), 309-320. [25] Khashman, A. (2009). Blood cell

Rapid identification of Yersinia pestis and Brucella melitensis by chip-based continuous flow PCR

NASA Astrophysics Data System (ADS)

Dietzsch, Michael; Hlawatsch, Nadine; Melzer, Falk; Tomaso, Herbert; Gärtner, Claudia; Neubauer, Heinrich

2012-06-01

To combat the threat of biological agents like Yersinia pestis and Brucella melitensis in bioterroristic scenarios requires fast, easy-to-use and safe identification systems. In this study we describe a system for rapid amplification of specific genetic markers for the identification of Yersinia pestis and Brucella melitensis. Using chip based PCR and continuous flow technology we were able to amplify the targets simultaneously with a 2-step reaction profile within 20 minutes. The subsequent analysis of amplified fragments by standard gel electrophoresis requires another 45 minutes. We were able to detect both pathogens within 75 minutes being much faster than most other nucleic acid amplification technologies.

Navigation system for minimally invasive esophagectomy: experimental study in a porcine model.

PubMed

Nickel, Felix; Kenngott, Hannes G; Neuhaus, Jochen; Sommer, Christof M; Gehrig, Tobias; Kolb, Armin; Gondan, Matthias; Radeleff, Boris A; Schaible, Anja; Meinzer, Hans-Peter; Gutt, Carsten N; Müller-Stich, Beat-Peter

2013-10-01

Navigation systems potentially facilitate minimally invasive esophagectomy and improve patient outcome by improving intraoperative orientation, position estimation of instruments, and identification of lymph nodes and resection margins. The authors' self-developed navigation system is highly accurate in static environments. This study aimed to test the overall accuracy of the navigation system in a realistic operating room scenario and to identify the different sources of error altering accuracy. To simulate a realistic environment, a porcine model (n = 5) was used with endoscopic clips in the esophagus as navigation targets. Computed tomography imaging was followed by image segmentation and target definition with the medical imaging interaction toolkit software. Optical tracking was used for registration and localization of animals and navigation instruments. Intraoperatively, the instrument was displayed relative to segmented organs in real time. The target registration error (TRE) of the navigation system was defined as the distance between the target and the navigation instrument tip. The TRE was measured on skin targets with the animal in the 0° supine and 25° anti-Trendelenburg position and on the esophagus during laparoscopic transhiatal preparation. On skin targets, the TRE was significantly higher in the 25° position, at 14.6 ± 2.7 mm, compared with the 0° position, at 3.2 ± 1.3 mm. The TRE on the esophagus was 11.2 ± 2.4 mm. The main source of error was soft tissue deformation caused by intraoperative positioning, pneumoperitoneum, surgical manipulation, and tissue dissection. The navigation system obtained acceptable accuracy with a minimally invasive transhiatal approach to the esophagus in a realistic experimental model. Thus the system has the potential to improve intraoperative orientation, identification of lymph nodes and adequate resection margins, and visualization of risk structures. Compensation methods for soft tissue deformation may lead to an even more accurate navigation system in the future.

A novel algorithm for finding optimal driver nodes to target control complex networks and its applications for drug targets identification.

PubMed

Guo, Wei-Feng; Zhang, Shao-Wu; Shi, Qian-Qian; Zhang, Cheng-Ming; Zeng, Tao; Chen, Luonan

2018-01-19

The advances in target control of complex networks not only can offer new insights into the general control dynamics of complex systems, but also be useful for the practical application in systems biology, such as discovering new therapeutic targets for disease intervention. In many cases, e.g. drug target identification in biological networks, we usually require a target control on a subset of nodes (i.e., disease-associated genes) with minimum cost, and we further expect that more driver nodes consistent with a certain well-selected network nodes (i.e., prior-known drug-target genes). Therefore, motivated by this fact, we pose and address a new and practical problem called as target control problem with objectives-guided optimization (TCO): how could we control the interested variables (or targets) of a system with the optional driver nodes by minimizing the total quantity of drivers and meantime maximizing the quantity of constrained nodes among those drivers. Here, we design an efficient algorithm (TCOA) to find the optional driver nodes for controlling targets in complex networks. We apply our TCOA to several real-world networks, and the results support that our TCOA can identify more precise driver nodes than the existing control-fucus approaches. Furthermore, we have applied TCOA to two bimolecular expert-curate networks. Source code for our TCOA is freely available from http://sysbio.sibcb.ac.cn/cb/chenlab/software.htm or https://github.com/WilfongGuo/guoweifeng . In the previous theoretical research for the full control, there exists an observation and conclusion that the driver nodes tend to be low-degree nodes. However, for target control the biological networks, we find interestingly that the driver nodes tend to be high-degree nodes, which is more consistent with the biological experimental observations. Furthermore, our results supply the novel insights into how we can efficiently target control a complex system, and especially many evidences on the practical strategic utility of TCOA to incorporate prior drug information into potential drug-target forecasts. Thus applicably, our method paves a novel and efficient way to identify the drug targets for leading the phenotype transitions of underlying biological networks.

Advanced miniature processing handware for ATR applications

NASA Technical Reports Server (NTRS)

Chao, Tien-Hsin (Inventor); Daud, Taher (Inventor); Thakoor, Anikumar (Inventor)

2003-01-01

A Hybrid Optoelectronic Neural Object Recognition System (HONORS), is disclosed, comprising two major building blocks: (1) an advanced grayscale optical correlator (OC) and (2) a massively parallel three-dimensional neural-processor. The optical correlator, with its inherent advantages in parallel processing and shift invariance, is used for target of interest (TOI) detection and segmentation. The three-dimensional neural-processor, with its robust neural learning capability, is used for target classification and identification. The hybrid optoelectronic neural object recognition system, with its powerful combination of optical processing and neural networks, enables real-time, large frame, automatic target recognition (ATR).

Methods and systems for Raman and optical cross-interrogation in flow-through silicon membranes

DOEpatents

Bond, Tiziana C.; Letant, Sonia E.

2014-09-09

Cross-interrogating photonic detection systems and methods are shown. A flow through photonic crystal membrane with a surface enhanced Raman scattering (SERS) substrate is provided with pores which are distributed along multiple regions. The pores of one region have walls to which a first type of target specific anchor can be attached, while pores of another region have walls to which a second type of target specific anchor can be attached. An optical arrangement out-of-plane to the SERS substrate is also provided for enhanced sensitivity and identification of target organisms.

Collaborative identification method for sea battlefield target based on deep convolutional neural networks

NASA Astrophysics Data System (ADS)

Zheng, Guangdi; Pan, Mingbo; Liu, Wei; Wu, Xuetong

2018-03-01

The target identification of the sea battlefield is the prerequisite for the judgment of the enemy in the modern naval battle. In this paper, a collaborative identification method based on convolution neural network is proposed to identify the typical targets of sea battlefields. Different from the traditional single-input/single-output identification method, the proposed method constructs a multi-input/single-output co-identification architecture based on optimized convolution neural network and weighted D-S evidence theory. The simulation results show that

Nuclear Security: Target Analysis-rev

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Surinder Paul; Gibbs, Philip W.; Bultz, Garl A.

2014-03-01

The objectives of this presentation are to understand target identification, including roll-up and protracted theft; evaluate target identification in the SNRI; recognize the target characteristics and consequence levels; and understand graded safeguards.

Multi-look fusion identification: a paradigm shift from quality to quantity in data samples

NASA Astrophysics Data System (ADS)

Wong, S.

2009-05-01

A multi-look identification method known as score-level fusion is found to be capable of achieving very high identification accuracy, even when low quality target signatures are used. Analysis using measured ground vehicle radar signatures has shown that a 97% correct identification rate can be achieved using this multi-look fusion method; in contrast, only a 37% accuracy rate is obtained when single target signature input is used. The results suggest that quantity can be used to replace quality of the target data in improving identification accuracy. With the advent of sensor technology, a large amount of target signatures of marginal quality can be captured routinely. This quantity over quality approach allows maximum exploitation of the available data to improve the target identification performance and this could have the potential of being developed into a disruptive technology.

Plant-bacterial pathogen interactions mediated by type III effectors.

PubMed

Feng, Feng; Zhou, Jian-Min

2012-08-01

Effectors secreted by the bacterial type III system play a central role in the interaction between Gram-negative bacterial pathogens and their host plants. Recent advances in the effector studies have helped cementing several key concepts concerning bacterial pathogenesis, plant immunity, and plant-pathogen co-evolution. Type III effectors use a variety of biochemical mechanisms to target specific host proteins or DNA for pathogenesis. The identifications of their host targets led to the identification of novel components of plant innate immune system. Key modules of plant immune signaling pathways such as immune receptor complexes and MAPK cascades have emerged as a major battle ground for host-pathogen adaptation. These modules are attacked by multiple type III effectors, and some components of these modules have evolved to actively sense the effectors and trigger immunity. Copyright © 2012 Elsevier Ltd. All rights reserved.

Developing Human-Machine Interfaces to Support Appropriate Trust and Reliance on Automated Combat Identification Systems (Developpement d’Interfaces Homme-Machine Pour Appuyer la Confiance dans les Systemes Automatises d’Identification au Combat)

DTIC Science & Technology

2008-03-31

on automation; the ‘response bias’ approach. This new approach is based on Signal Detection Theory (SDT) (Macmillan & Creelman , 1991; Wickens...SDT), response bias will vary with the expectation of the target probability, whereas their sensitivity will stay constant (Macmillan & Creelman ...measures, C has the simplest statistical properties (Macmillan & Creelman , 1991, p273), and it was also the measure used in Dzindolet et al.’s study

Advanced surface-enhanced Raman gene probe systems and methods thereof

DOEpatents

Vo-Dinh, Tuan

2001-01-01

The subject invention is a series of methods and systems for using the Surface-Enhanced Raman (SER)-labeled Gene Probe for hybridization, detection and identification of SER-labeled hybridized target oligonucleotide material comprising the steps of immobilizing SER-labeled hybridized target oligonucleotide material on a support means, wherein the SER-labeled hybridized target oligonucleotide material comprise a SER label attached either to a target oligonucleotide of unknown sequence or to a gene probe of known sequence complementary to the target oligonucleotide sequence, the SER label is unique for the target oligonucleotide strands of a particular sequence wherein the SER-labeled oligonucleotide is hybridized to its complementary oligonucleotide strand, then the support means having the SER-labeled hybridized target oligonucleotide material adsorbed thereon is SERS activated with a SERS activating means, then the support means is analyzed.

Treat the brain and treat the periphery: toward a holistic approach to major depressive disorder.

PubMed

Zheng, Xiao; Zhang, Xueli; Wang, Guangji; Hao, Haiping

2015-05-01

The limited medication for major depressive disorder (MDD) against an ever-rising disease burden presents an urgent need for therapeutic innovations. During recent years, studies looking at the systems regulation of mental health and disease have shown a remarkably powerful control of MDD by systemic signals. Meanwhile, the identification of a host of targets outside the brain opens the way to treat MDD by targeting systemic signals. We examine these emerging findings and consider the implications for current thinking regarding MDD pathogenesis and treatment. We highlight the opportunities and challenges of a periphery-targeting strategy and propose its incorporation into a holistic approach. Copyright © 2015 Elsevier Ltd. All rights reserved.

Ancient deltas on Mars: outstanding targets for martian habitability?

NASA Astrophysics Data System (ADS)

Gupta, S.; Fawdon, P.; Grindrod, P. M.; Balme, M. R.; Hauber, E.; Warner, N. H.; Muller, J. P.

2014-12-01

The identification of putative ancient deltaic sedimentary systems on Mars has been both exciting and controversial. Our excitement is elicted by the potential provided by deltas as evidence for standing bodies of water associated with the deltas, and the resulting implications for both the ancient climate of Mars and ancient habitability. The controversy stems from how confident can we be in the identification of ancient deltaic systems from orbital data, and how robust are our assertions about the habitability potential of such settings. Delta systems in particular are key astrobiological targets because at their distal toes fine-grained sediment (ie., clays) settle from suspension in a lower energy setting and they are commonly characterised by high rates of sedimentation. This leads to high preservation potential of biosignatures. Targeting of future Mars rovers to investigate deltaic landing sites requires better understanding of these issues to reduce exploration risk. In this presentation, we describe the key criteria that enable us to make robust interpretations of deltaic stratigraphy and constrain delta evolution for martian systems. In particular, the past 10 years has seen in a revolution in our process understanding of terrestrial delta systems through a combination of field, experimental and numerical modelling studies. Analysis of martian deltas has much to gain from these results. We go on to consider why deltaic systems offer potential as astrobiological target paleoenvironments. We use the exhumed delta system (Hypanis delta system) at the termination of Hypanis Vallis, 11.8°N, 314.96°E as a case example. This system, situated in Xanthe Terra, comprises layered sedimentary rocks with an overall multi-lobate geometry and associated inverted channel networks. The Hypanis 'delta' is a proposed landing site for the ExoMars rover and also for the NASA 2020 mission.

Identification of the Transcriptional Targets of FOXP2, a Gene Linked to Speech and Language, in Developing Human Brain

PubMed Central

Spiteri, Elizabeth ; Konopka, Genevieve ; Coppola, Giovanni ; Bomar, Jamee ; Oldham, Michael ; Ou, Jing ; Vernes, Sonja C. ; Fisher, Simon E. ; Ren, Bing ; Geschwind, Daniel H. 

2007-01-01

Mutations in FOXP2, a member of the forkhead family of transcription factor genes, are the only known cause of developmental speech and language disorders in humans. To date, there are no known targets of human FOXP2 in the nervous system. The identification of FOXP2 targets in the developing human brain, therefore, provides a unique tool with which to explore the development of human language and speech. Here, we define FOXP2 targets in human basal ganglia (BG) and inferior frontal cortex (IFC) by use of chromatin immunoprecipitation followed by microarray analysis (ChIP-chip) and validate the functional regulation of targets in vitro. ChIP-chip identified 285 FOXP2 targets in fetal human brain; statistically significant overlap of targets in BG and IFC indicates a core set of 34 transcriptional targets of FOXP2. We identified targets specific to IFC or BG that were not observed in lung, suggesting important regional and tissue differences in FOXP2 activity. Many target genes are known to play critical roles in specific aspects of central nervous system patterning or development, such as neurite outgrowth, as well as plasticity. Subsets of the FOXP2 transcriptional targets are either under positive selection in humans or differentially expressed between human and chimpanzee brain. This is the first ChIP-chip study to use human brain tissue, making the FOXP2-target genes identified in these studies important to understanding the pathways regulating speech and language in the developing human brain. These data provide the first insight into the functional network of genes directly regulated by FOXP2 in human brain and by evolutionary comparisons, highlighting genes likely to be involved in the development of human higher-order cognitive processes. PMID:17999357

From drug to protein: using yeast genetics for high-throughput target discovery.

PubMed

Armour, Christopher D; Lum, Pek Yee

2005-02-01

The budding yeast Saccharomyces cerevisiae has long been an effective eukaryotic model system for understanding basic cellular processes. The genetic tractability and ease of manipulation in the laboratory make yeast well suited for large-scale chemical and genetic screens. Several recent studies describing the use of yeast genetics for high-throughput drug target identification are discussed in this review.

Sensor Research Targets Smart Building Technology Using Radio-Frequency

Science.gov Websites

a battery-free radio-frequency identification (RFID) sensor network with spatiotemporal pattern network based data fusion system for human presence sensing, with ARPA-E awarding the team $2 million over

Target identification using Zernike moments and neural networks

NASA Astrophysics Data System (ADS)

Azimi-Sadjadi, Mahmood R.; Jamshidi, Arta A.; Nevis, Andrew J.

2001-10-01

The development of an underwater target identification algorithm capable of identifying various types of underwater targets, such as mines, under different environmental conditions pose many technical problems. Some of the contributing factors are: targets have diverse sizes, shapes and reflectivity properties. Target emplacement environment is variable; targets may be proud or partially buried. Environmental properties vary significantly from one location to another. Bottom features such as sand, rocks, corals, and vegetation can conceal a target whether it is partially buried or proud. Competing clutter with responses that closely resemble those of the targets may lead to false positives. All the problems mentioned above contribute to overly difficult and challenging conditions that could lead to unreliable algorithm performance with existing methods. In this paper, we developed and tested a shape-dependent feature extraction scheme that provides features invariant to rotation, size scaling and translation; properties that are extremely useful for any target classification problem. The developed schemes were tested on an electro-optical imagery data set collected under different environmental conditions with variable background, range and target types. The electro-optic data set was collected using a Laser Line Scan (LLS) sensor by the Coastal Systems Station (CSS), located in Panama City, Florida. The performance of the developed scheme and its robustness to distortion, rotation, scaling and translation was also studied.

Isolation of Mycobacterium massiliense from a corneal biopsy in India.

PubMed

Kulandai, Lily Therese; Lakshmipathy, Dhanurekha; Ramasubban, Gayathri; Rao, Madhavan Hajib Narahari

2014-12-01

Rapidly growing mycobacteria (RGM) are ubiquitous and are usually considered as saprophytes, and have been recovered from the environment, particularly in dust, watery soil and water distribution systems. However, Mycobacterium massiliense is a rare causative agent of ocular infection. We report a case of M. massiliense in a 44-year-old female with signs and symptoms of a corneal ulcer. We carried out PCR-based DNA sequencing targeting the hsp 65 gene for the identification of M. massiliense . To confirm the identification, we also performed PCR-based RFLP targeting the hsp65 gene and PCR-based DNA sequencing targeting the internal transcribed spacer region, which showed 97 % nucleotide identity with M. massiliense . To the best of our knowledge, this is the first study in India to report the detection of M. massiliense from a corneal biopsy.

Fast and Confident: Postdicting Eyewitness Identification Accuracy in a Field Study

ERIC Educational Resources Information Center

Sauerland, Melanie; Sporer, Siegfried L.

2009-01-01

The combined postdictive value of postdecision confidence, decision time, and Remember-Know-Familiar (RKF) judgments as markers of identification accuracy was evaluated with 10 targets and 720 participants. In a pedestrian area, passers-by were asked for directions. Identifications were made from target-absent or target-present lineups. Fast…

Target identification for small bioactive molecules: finding the needle in the haystack.

PubMed

Ziegler, Slava; Pries, Verena; Hedberg, Christian; Waldmann, Herbert

2013-03-04

Identification and confirmation of bioactive small-molecule targets is a crucial, often decisive step both in academic and pharmaceutical research. Through the development and availability of several new experimental techniques, target identification is, in principle, feasible, and the number of successful examples steadily grows. However, a generic methodology that can successfully be applied in the majority of the cases has not yet been established. Herein we summarize current methods for target identification of small molecules, primarily for a chemistry audience but also the biological community, for example, the chemist or biologist attempting to identify the target of a given bioactive compound. We describe the most frequently employed experimental approaches for target identification and provide several representative examples illustrating the state-of-the-art. Among the techniques currently available, protein affinity isolation using suitable small-molecule probes (pulldown) and subsequent mass spectrometric analysis of the isolated proteins appears to be most powerful and most frequently applied. To provide guidance for rapid entry into the field and based on our own experience we propose a typical workflow for target identification, which centers on the application of chemical proteomics as the key step to generate hypotheses for potential target proteins. Copyright © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Planning the data transition of a VLDB: a case study

NASA Astrophysics Data System (ADS)

Finken, Shirley J.

1997-02-01

This paper describes the technical and programmatic plans for moving and checking certain data from the IDentification Automated Services (IDAS) system to the new Interstate Identification Index/Federal Bureau of Investigation (III/FBI) Segment database--one of the three components of the Integrated Automated Fingerprint Identification System (IAFIS) being developed by the Federal Bureau of Investigation, Criminal Justice Information Services Division. Transitioning IDAS to III/FBI includes putting the data into an entirely new target database structure (i.e. from IBM VSAM files to ORACLE7 RDBMS tables). Only four IDAS files were transitioned (CCN, CCR, CCA, and CRS), but their total estimated size is at 500 Gb of data. Transitioning of this Very Large Database is planned as two processes.

Optimization of a Multi-Stage ATR System for Small Target Identification

NASA Technical Reports Server (NTRS)

Lin, Tsung-Han; Lu, Thomas; Braun, Henry; Edens, Western; Zhang, Yuhan; Chao, Tien- Hsin; Assad, Christopher; Huntsberger, Terrance

2010-01-01

An Automated Target Recognition system (ATR) was developed to locate and target small object in images and videos. The data is preprocessed and sent to a grayscale optical correlator (GOC) filter to identify possible regionsof- interest (ROIs). Next, features are extracted from ROIs based on Principal Component Analysis (PCA) and sent to neural network (NN) to be classified. The features are analyzed by the NN classifier indicating if each ROI contains the desired target or not. The ATR system was found useful in identifying small boats in open sea. However, due to "noisy background," such as weather conditions, background buildings, or water wakes, some false targets are mis-classified. Feedforward backpropagation and Radial Basis neural networks are optimized for generalization of representative features to reduce false-alarm rate. The neural networks are compared for their performance in classification accuracy, classifying time, and training time.

Impact of rapid identification of positive blood cultures using the Verigene system on antibiotic prescriptions: A prospective study of community-onset bacteremia in a tertiary hospital in Japan.

PubMed

Hayakawa, Kayoko; Mezaki, Kazuhisa; Kobayakawa, Masao; Yamamoto, Kei; Mutoh, Yoshikazu; Tsuboi, Motoyuki; Hasimoto, Takehiro; Nagamatsu, Maki; Kutsuna, Satoshi; Takeshita, Nozomi; Katanami, Yuichi; Ishikane, Masahiro; Ohmagari, Norio

2017-01-01

Rapid identification of positive blood cultures is important for initiation of optimal treatment in septic patients. Effects of automated, microarray-based rapid identification systems on antibiotic prescription against community-onset bacteremia (COB) remain unclear. We prospectively enrolled 177 patients with 185 COB episodes (occurring within 72 h of admission) over 17 months. Bacteremia episodes due to gram-positive bacteria (GP) and gram-negative bacteria (GN) in the same patient were counted separately. For GP bacteremia, patients with ≥2 sets of positive blood cultures were included. The primary study objective was evaluating the rates of antibiotic prescription changes within 2 days of rapid identification using the Verigene system. Bacteremia due to GN and GP included 144/185 (77.8%) and 41/185 (22.2%) episodes, respectively. Antibiotic prescription changes occurred in 51/185 cases (27.6% [95%CI:21.3-34.6%]) after Verigene analysis and 70/185 cases (37.8% [30.8-45.2%]) after conventional identification and susceptibility testing. Prescription changes after Verigene identification were more frequent in GP (17/41[41.5%]) than in GN (34/144[23.5%]). Among bacteremia due to single pathogen targeted by Verigene test, bacterial identification agreement between the two tests was high (GP: 38/39[97.4%], GN: 116/116[100%]). The Verigene test correctly predicted targeted antimicrobial resistance. The durations between the initiation of incubation and reporting of the results for the Verigene system and conventional test was 28.3 h (IQR: 25.8-43.4 h) and 90.6 h (68.3-118.4 h), respectively. In only four of the seven episodes of COB in which two isolates were identified by conventional tests, the Verigene test correctly identified both organisms. We observed a high rate of antibiotic prescription changes after the Verigene test in a population with COB especially in GP. The Verigene test would be a useful tool in antimicrobial stewardship programs among patients with COB.

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering.

PubMed

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M Teresa; Buchholz, Frank

2016-07-22

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets.

Detection of small surface vessels in near, medium, and far infrared spectral bands

NASA Astrophysics Data System (ADS)

Dulski, R.; Milewski, S.; Kastek, M.; Trzaskawka, P.; Szustakowski, M.; Ciurapinski, W.; Zyczkowski, M.

2011-11-01

Protection of naval bases and harbors requires close co-operation between security and access control systems covering land areas and those monitoring sea approach routes. The typical location of naval bases and harbors - usually next to a large city - makes it difficult to detect and identify a threat in the dense regular traffic of various sea vessels (i.e. merchant ships, fishing boats, tourist ships). Due to the properties of vessel control systems, such as AIS (Automatic Identification System), and the effectiveness of radar and optoelectronic systems against different targets it seems that fast motor boats called RIB (Rigid Inflatable Boat) could be the most serious threat to ships and harbor infrastructure. In the paper the process and conditions for the detection and identification of high-speed boats in the areas of ports and naval bases in the near, medium and far infrared is presented. Based on the results of measurements and recorded thermal images the actual temperature contrast delta T (RIB / sea) will be determined, which will further allow to specify the theoretical ranges of detection and identification of the RIB-type targets for an operating security system. The data will also help to determine the possible advantages of image fusion where the component images are taken in different spectral ranges. This will increase the probability of identifying the object by the multi-sensor security system equipped additionally with the appropriate algorithms for detecting, tracking and performing the fusion of images from the visible and infrared cameras.

Structural systems pharmacology: a new frontier in discovering novel drug targets.

PubMed

Tan, Hepan; Ge, Xiaoxia; Xie, Lei

2013-08-01

The modern target-based drug discovery process, characterized by the one-drug-one-gene paradigm, has been of limited success. In contrast, phenotype-based screening produces thousands of active compounds but gives no hint as to what their molecular targets are or which ones merit further research. This presents a question: What is a suitable target for an efficient and safe drug? In this paper, we argue that target selection should take into account the proteome-wide energetic and kinetic landscape of drug-target interactions, as well as their cellular and organismal consequences. We propose a new paradigm of structural systems pharmacology to deconvolute the molecular targets of successful drugs as well as to identify druggable targets and their drug-like binders. Here we face two major challenges in structural systems pharmacology: How do we characterize and analyze the structural and energetic origins of drug-target interactions on a proteome scale? How do we correlate the dynamic molecular interactions to their in vivo activity? We will review recent advances in developing new computational tools for biophysics, bioinformatics, chemoinformatics, and systems biology related to the identification of genome-wide target profiles. We believe that the integration of these tools will realize structural systems pharmacology, enabling us to both efficiently develop effective therapeutics for complex diseases and combat drug resistance.

System identification for Space Station Freedom using observer/Kalman filter Markov parameters. M.S. Thesis

NASA Technical Reports Server (NTRS)

Papadopoulos, Michael; Tolson, Robert H.

1993-01-01

The Modal Identification Experiment (MIE) is a proposed experiment to define the dynamic characteristics of Space Station Freedom. Previous studies emphasized free-decay modal identification. The feasibility of using a forced response method (Observer/Kalman Filter Identification (OKID)) is addressed. The interest in using OKID is to determine the input mode shape matrix which can be used for controller design or control-structure interaction analysis, and investigate if forced response methods may aid in separating closely spaced modes. A model of the SC-7 configuration of Space Station Freedom was excited using simulated control system thrusters to obtain acceleration output. It is shown that an 'optimum' number of outputs exists for OKID. To recover global mode shapes, a modified method called Global-Local OKID was developed. This study shows that using data from a long forced response followed by free-decay leads to the 'best' modal identification. Twelve out of the thirteen target modes were identified for such an output.

Radiological assessment of target materials for accelerator transmutation of waste (ATW) applications

NASA Astrophysics Data System (ADS)

Vickers, Linda Diane

This dissertation issues the first published document of the radiation absorbed dose rate (rad-h-1) to tissue from radioactive spallation products in Ta, W, Pb, Bi, and LBE target materials used in Accelerator Transmutation of Waste (ATW) applications. No previous works have provided an estimate of the absorbed dose rate (rad-h-1) from activated targets for ATW applications. The results of this dissertation are useful for planning the radiological safety assessment to personnel, and for the design, construction, maintenance, and disposition of target materials of high-energy particle accelerators for ATW applications (Charlton, 1996). In addition, this dissertation provides the characterization of target materials of high-energy particle accelerators for the parameters of: (1) spallation neutron yield (neutrons/proton), (2) spallation products yield (nuclides/proton), (3) energy-dependent spallation neutron fluence distribution, (4) spallation neutron flux, (5) identification of radioactive spallation products for consideration in safety of personnel to high radiation dose rates, and (6) identification of the optimum geometrical dimensions for the target applicable to the maximum radial spallation neutron leakage from the target. Pb and Bi target materials yielded the lowest absorbed dose rates (rad-h -1) for a 10-year irradiation/50-year decay scheme, and would be the preferred target materials for consideration of the radiological safety of personnel during ATW operations. A beneficial characteristic of these target materials is that they do not produce radioactive transuranic isotopes, which have very long half-lives and require special handling and disposition requirements. Furthermore, the targets are not considered High-Level Waste (HLW) such as reactor spent fuel for disposal purposes. It is a basic ATW system requirement that the spallation target after it has been expended should be disposable as Class C low-level radioactive waste. Therefore, the disposal of Pb and Bi targets would be optimally beneficial to the economy and environment. Future studies should relate the target performance to other system parameters, specifically solid and liquid blanket systems that contain the radioactive waste to be transmuted. The methodology of this dissertation may be applied to any target material of a high-energy particle accelerator.

Identification of Enterobacteriaceae by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry using the VITEK MS system.

PubMed

Richter, S S; Sercia, L; Branda, J A; Burnham, C-A D; Bythrow, M; Ferraro, M J; Garner, O B; Ginocchio, C C; Jennemann, R; Lewinski, M A; Manji, R; Mochon, A B; Rychert, J A; Westblade, L F; Procop, G W

2013-12-01

This multicenter study evaluated the accuracy of matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry identifications from the VITEK MS system (bioMérieux, Marcy l'Etoile, France) for Enterobacteriaceae typically encountered in the clinical laboratory. Enterobacteriaceae isolates (n = 965) representing 17 genera and 40 species were analyzed on the VITEK MS system (database v2.0), in accordance with the manufacturer's instructions. Colony growth (≤72 h) was applied directly to the target slide. Matrix solution (α-cyano-4-hydroxycinnamic acid) was added and allowed to dry before mass spectrometry analysis. On the basis of the confidence level, the VITEK MS system provided a species, genus only, or no identification for each isolate. The accuracy of the mass spectrometric identification was compared to 16S rRNA gene sequencing performed at MIDI Labs (Newark, DE). Supplemental phenotypic testing was performed at bioMérieux when necessary. The VITEK MS result agreed with the reference method identification for 96.7% of the 965 isolates tested, with 83.8% correct to the species level and 12.8% limited to a genus-level identification. There was no identification for 1.7% of the isolates. The VITEK MS system misidentified 7 isolates (0.7 %) as different genera. Three Pantoea agglomerans isolates were misidentified as Enterobacter spp. and single isolates of Enterobacter cancerogenus, Escherichia hermannii, Hafnia alvei, and Raoultella ornithinolytica were misidentified as Klebsiella oxytoca, Citrobacter koseri, Obesumbacterium proteus, and Enterobacter aerogenes, respectively. Eight isolates (0.8 %) were misidentified as a different species in the correct genus. The VITEK MS system provides reliable mass spectrometric identifications for Enterobacteriaceae.

Effects of postidentification feedback on eyewitness identification and nonidentification confidence.

PubMed

Semmler, Carolyn; Brewer, Neil; Wells, Gary L

2004-04-01

Two experiments investigated new dimensions of the effect of confirming feedback on eyewitness identification confidence using target-absent and target-present lineups and (previously unused) unbiased witness instructions (i.e., "offender not present" option highlighted). In Experiment 1, participants viewed a crime video and were later asked to try to identify the thief from an 8-person target-absent photo array. Feedback inflated witness confidence for both mistaken identifications and correct lineup rejections. With target-present lineups in Experiment 2, feedback inflated confidence for correct and mistaken identifications and lineup rejections. Although feedback had no influence on the confidence-accuracy correlation, it produced clear overconfidence. Confidence inflation varied with the confidence measure reference point (i.e., retrospective vs. current confidence) and identification response latency.

Structure based drug discovery for designing leads for the non-toxic metabolic targets in multi drug resistant Mycobacterium tuberculosis.

PubMed

Kaur, Divneet; Mathew, Shalu; Nair, Chinchu G S; Begum, Azitha; Jainanarayan, Ashwin K; Sharma, Mukta; Brahmachari, Samir K

2017-12-21

The problem of drug resistance and bacterial persistence in tuberculosis is a cause of global alarm. Although, the UN's Sustainable Development Goals for 2030 has targeted a Tb free world, the treatment gap exists and only a few new drug candidates are in the pipeline. In spite of large information from medicinal chemistry to 'omics' data, there has been a little effort from pharmaceutical companies to generate pipelines for the development of novel drug candidates against the multi drug resistant Mycobacterium tuberculosis. In the present study, we describe an integrated methodology; utilizing systems level information to optimize ligand selection to lower the failure rates at the pre-clinical and clinical levels. In the present study, metabolic targets (Rv2763c, Rv3247c, Rv1094, Rv3607c, Rv3048c, Rv2965c, Rv2361c, Rv0865, Rv0321, Rv0098, Rv0390, Rv3588c, Rv2244, Rv2465c and Rv2607) in M. tuberculosis, identified using our previous Systems Biology and data-intensive genome level analysis, have been used to design potential lead molecules, which are likely to be non-toxic. Various in silico drug discovery tools have been utilized to generate small molecular leads for each of the 15 targets with available crystal structures. The present study resulted in identification of 20 novel lead molecules including 4 FDA approved drugs (droxidropa, tetroxoprim, domperidone and nemonapride) which can be further taken for drug repurposing. This comprehensive integrated methodology, with both experimental and in silico approaches, has the potential to not only tackle the MDR form of Mtb but also the most important persister population of the bacterium, with a potential to reduce the failures in the Tb drug discovery. We propose an integrated approach of systems and structural biology for identifying targets that address the high attrition rate issue in lead identification and drug development We expect that this system level analysis will be applicable for identification of drug candidates to other pathogenic organisms as well.

Social judgment of abortion: a black-sheep effect in a Catholic sheepfold.

PubMed

Bègue, L

2001-10-01

French Catholic participants (N = 340) with high or low religious identification read 1 of 8 scenarios presented as an interview with a female target 2 months after she had had an abortion. The experimental device varied situational pressure (pressure vs. no pressure), the target's religious social identity (Catholic vs. neutral), and the consequences of abortion for the target (positive vs. negative). The participants then rated the acceptability of the target's decision. The participants judged abortion more negatively in the no-pressure condition. Moreover, the participants with high religious identification judged abortion more negatively than did those with low religious identification. In partial support of a black-sheep effect, the participants with high religious identification judged the Catholic target more negatively than they judged the neutral one in some conditions (pressure, negative consequences). In other conditions (no pressure, both positive and negative consequences), the participants with low religious identification judged the Catholic target more positively than they judged the neutral one.

Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders.

PubMed

Fang, Jiansong; Gao, Li; Ma, Huili; Wu, Qihui; Wu, Tian; Wu, Jun; Wang, Qi; Cheng, Feixiong

2017-01-01

Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), c aenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders.

Quantitative and Systems Pharmacology 3. Network-Based Identification of New Targets for Natural Products Enables Potential Uses in Aging-Associated Disorders

PubMed Central

Fang, Jiansong; Gao, Li; Ma, Huili; Wu, Qihui; Wu, Tian; Wu, Jun; Wang, Qi; Cheng, Feixiong

2017-01-01

Aging that refers the accumulation of genetic and physiology changes in cells and tissues over a lifetime has been shown a high risk of developing various complex diseases, such as neurodegenerative disease, cardiovascular disease and cancer. Over the past several decades, natural products have been demonstrated as anti-aging interveners via extending lifespan and preventing aging-associated disorders. In this study, we developed an integrated systems pharmacology infrastructure to uncover new indications for aging-associated disorders by natural products. Specifically, we incorporated 411 high-quality aging-associated human genes or human-orthologous genes from mus musculus (MM), saccharomyces cerevisiae (SC), caenorhabditis elegans (CE), and drosophila melanogaster (DM). We constructed a global drug-target network of natural products by integrating both experimental and computationally predicted drug-target interactions (DTI). We further built the statistical network models for identification of new anti-aging indications of natural products through integration of the curated aging-associated genes and drug-target network of natural products. High accuracy was achieved on the network models. We showcased several network-predicted anti-aging indications of four typical natural products (caffeic acid, metformin, myricetin, and resveratrol) with new mechanism-of-actions. In summary, this study offers a powerful systems pharmacology infrastructure to identify natural products for treatment of aging-associated disorders. PMID:29093681

Hazard identification and risk assessment for biologics targeting the immune system.

PubMed

Weir, Andrea B

2008-01-01

Biologic pharmaceuticals include a variety of products, such as monoclonal antibodies, fusion proteins and cytokines. Products in those classes include immunomodulatory biologics, which are intended to enhance or diminish the activity of the immune system. Immunomodulatory biologics have been approved by the U.S. FDA for a variety of indications, including cancer and inflammatory conditions. Prior to gaining approval for marketing, sponsoring companies for all types of products must demonstrate a product's safety in toxicology studies conducted in animals and show safety and efficacy in clinical trials conducted in patients. The overall goal of toxicology studies, which applies to immunomodulatory and other product types, is to identify the hazards that products pose to humans. Because biologics are generally highly selective for specific targets (receptors/epitopes), conducting toxicology studies in animal models with the target is essential. Such animals are referred to as pharmacologically relevant. Endpoints routinely included in toxicology studies, such as hematology, organ weight and histopathology, can be used to assess the effect of a product on the structure of the immune system. Additionally, specialized endpoints, such as immunophenotyping and immune function tests, can be used to define effects of immunomodulatory products on the immune system. Following hazard identification, risks posed to patients are assessed and managed. Risks can be managed through clinical trial design and risk communication, a practice that applies to immunomodulatory and other product types. Examples of risk management in clinical trial design include establishing a safe starting dose, defining the appropriate patient population and establishing appropriate patient monitoring. Risk communication starts during clinical trials and continues after product approval. A combination of hazard identification, risk assessment and risk management allows for drug development to proceed with minimum risks to patients.

Neural Network Target Identification System for False Alarm Reduction

NASA Technical Reports Server (NTRS)

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.

Targeted Mutagenesis in Rice Using TALENs and the CRISPR/Cas9 System.

PubMed

Endo, Masaki; Nishizawa-Yokoi, Ayako; Toki, Seiichi

2016-01-01

Sequence-specific nucleases (SSNs), such as zinc-finger nucleases (ZFNs), transcription activator-like effector nucleases (TALENs), and the clustered regularly interspersed short palindromic repeats (CRISPR)/CRISPR-associated protein 9 nuclease (Cas9) system, are powerful tools for understanding gene function and for developing novel traits in plants. In plant species for which transformation and regeneration systems using protoplasts are not yet established, direct delivery to nuclei of SSNs either in the form of RNA or protein is difficult. Thus, Agrobacterium-mediated transformation of SSN expression constructs in cultured cells is a practical means of delivering targeted mutagenesis in some plant species including rice. Because targeted mutagenesis occurs stochastically in transgenic cells and SSN-mediated targeted mutagenesis often leads to no selectable phenotype, identification of highly mutated cell lines is a critical step in obtaining regenerated plants with desired mutations.

A metabolic network approach for the identification and prioritization of antimicrobial drug targets

PubMed Central

Chavali, Arvind K.; D’Auria, Kevin M.; Hewlett, Erik L.; Pearson, Richard D.; Papin, Jason A.

2012-01-01

For many infectious diseases, novel treatment options are needed to address problems with cost, toxicity and resistance to current drugs. Systems biology tools can be used to gain valuable insight into pathogenic processes and aid in expediting drug discovery. In the past decade, constraint-based modeling of genome-scale metabolic networks has become widely used. Focusing on pathogen metabolic networks, we review in silico strategies to identify effective drug targets, and we highlight recent successes as well as limitations associated with such computational analyses. We further discuss how accounting for the host environment and even targeting the host may offer new therapeutic options. These systems-level approaches are beginning to provide novel avenues for drug targeting against infectious agents. PMID:22300758

A systems biology perspective on plant-microbe interactions: biochemical and structural targets of pathogen effectors.

PubMed

Pritchard, Leighton; Birch, Paul

2011-04-01

Plants have biochemical defences against stresses from predators, parasites and pathogens. In this review we discuss the interaction of plant defences with microbial pathogens such as bacteria, fungi and oomycetes, and viruses. We examine principles of complex dynamic networks that allow identification of network components that are differentially and predictably sensitive to perturbation, thus making them likely effector targets. We relate these principles to recent developments in our understanding of known effector targets in plant-pathogen systems, and propose a systems-level framework for the interpretation and modelling of host-microbe interactions mediated by effectors. We describe this framework briefly, and conclude by discussing useful experimental approaches for populating this framework. Copyright © 2010 Elsevier Ireland Ltd. All rights reserved.

Taqman real-time quantitative PCR for identification of western flower thrip (Frankliniella occidentalis) for plant quarantine

PubMed Central

Huang, K. S.; Lee, S. E.; Yeh, Y.; Shen, G. S.; Mei, E.; Chang, C. M.

2010-01-01

Western flower thrip (Frankliniella occidentalis) is a major global pest of agricultural products. It directly damages crops through feeding, oviposition activity or transmission of several plant viruses. We describe a Taqman real-time quantitative PCR detection system, which can rapidly identify F. occidentalis from thrips larvae to complement the traditional morphological identification. The data showed that our detection system targeted on the ribosomal RNA gene regions of F. occidentalis has high sensitivity and specificity. The rapid method can be used for on-site testing of samples at ports-of-entry in the future. PMID:20129946

Taqman real-time quantitative PCR for identification of western flower thrip (Frankliniella occidentalis) for plant quarantine.

PubMed

Huang, K S; Lee, S E; Yeh, Y; Shen, G S; Mei, E; Chang, C M

2010-08-23

Western flower thrip (Frankliniella occidentalis) is a major global pest of agricultural products. It directly damages crops through feeding, oviposition activity or transmission of several plant viruses. We describe a Taqman real-time quantitative PCR detection system, which can rapidly identify F. occidentalis from thrips larvae to complement the traditional morphological identification. The data showed that our detection system targeted on the ribosomal RNA gene regions of F. occidentalis has high sensitivity and specificity. The rapid method can be used for on-site testing of samples at ports-of-entry in the future.

Organizational Potential of Scientific Work in the System of Neuromanagement by the Example of Higher Education

ERIC Educational Resources Information Center

Nikolaevskaya, Olga

2015-01-01

Neuromanagement of higher education is an effective tool for the development of higher education, professional identification of specialist, increase of the professional authority and prestige of modern scientific and research work. The target point of neuromanagement system is competitiveness of the modern university graduate whose competence…

Recursive Inversion By Finite-Impulse-Response Filters

NASA Technical Reports Server (NTRS)

Bach, Ralph E., Jr.; Baram, Yoram

1991-01-01

Recursive approximation gives least-squares best fit to exact response. Algorithm yields finite-impulse-response approximation of unknown single-input/single-output, causal, time-invariant, linear, real system, response of which is sequence of impulses. Applicable to such system-inversion problems as suppression of echoes and identification of target from its scatter response to incident impulse.

[Identification of proteins interacting with the circadian clock protein PER1 in tumors using bacterial two-hybrid system technique].

PubMed

Zhang, Yu; Yao, Youlin; Jiang, Siyuan; Lu, Yilu; Liu, Yunqiang; Tao, Dachang; Zhang, Sizhong; Ma, Yongxin

2015-04-01

To identify protein-protein interaction partners of PER1 (period circadian protein homolog 1), key component of the molecular oscillation system of the circadian rhythm in tumors using bacterial two-hybrid system technique. Human cervical carcinoma cell Hela library was adopted. Recombinant bait plasmid pBT-PER1 and pTRG cDNA plasmid library were cotransformed into the two-hybrid system reporter strain cultured in a special selective medium. Target clones were screened. After isolating the positive clones, the target clones were sequenced and analyzed. Fourteen protein coding genes were identified, 4 of which were found to contain whole coding regions of genes, which included optic atrophy 3 protein (OPA3) associated with mitochondrial dynamics and homo sapiens cutA divalent cation tolerance homolog of E. coli (CUTA) associated with copper metabolism. There were also cellular events related proteins and proteins which are involved in biochemical reaction and signal transduction-related proteins. Identification of potential interacting proteins with PER1 in tumors may provide us new insights into the functions of the circadian clock protein PER1 during tumorigenesis.

Trust and reliance on an automated combat identification system.

PubMed

Wang, Lu; Jamieson, Greg A; Hollands, Justin G

2009-06-01

We examined the effects of aid reliability and reliability disclosure on human trust in and reliance on a combat identification (CID) aid. We tested whether trust acts as a mediating factor between belief in and reliance on a CID aid. Individual CID systems have been developed to reduce friendly fire incidents. However, these systems cannot positively identify a target that does not have a working transponder. Therefore, when the feedback is "unknown", the target could be hostile, neutral, or friendly. Soldiers have difficulty relying on this type of imperfect automation appropriately. In manual and aided conditions, 24 participants completed a simulated CID task. The reliability of the aid varied within participants, half of whom were told the aid reliability level. We used the difference in response bias values across conditions to measure automation reliance. Response bias varied more appropriately with the aid reliability level when it was disclosed than when not. Trust in aid feedback correlated with belief in aid reliability and reliance on aid feedback; however, belief was not correlated with reliance. To engender appropriate reliance on CID systems, users should be made aware of system reliability. The findings can be applied to the design of information displays for individual CID systems and soldier training.

Toward the development of portable miniature intelligent electronic color identification devices

NASA Astrophysics Data System (ADS)

Nicolau, Dan V., Jr.; Livingston, Peter; Jahshan, David; Evans, Rob

2004-03-01

The identification and differentiation of colours is a relatively problematic task for colour-impaired and partially vision-impaired persons and an impossible one for completely blind. In various contexts, this leads to a loss of independence or an increased risk of harm. The identification of colour using optoelectronic devices, on the other hand, can be done precisely and inexpensively. Additionally, breakthroughs in miniaturising and integrating colour sensors into biological systems may lead to significant advances in electronic implants for alleviating blindness. Here we present a functional handheld device developed for the identification of colour, intended for use by the vision-impaired. We discuss the features and limitations of the device and describe in detail one target application - the identification of different banknote denominations by the blind.

Recovery Based Nanowire Field-Effect Transistor Detection of Pathogenic Avian Influenza DNA

NASA Astrophysics Data System (ADS)

Lin, Chih-Heng; Chu, Chia-Jung; Teng, Kang-Ning; Su, Yi-Jr; Chen, Chii-Dong; Tsai, Li-Chu; Yang, Yuh-Shyong

2012-02-01

Fast and accurate diagnosis is critical in infectious disease surveillance and management. We proposed a DNA recovery system that can easily be adapted to DNA chip or DNA biosensor for fast identification and confirmation of target DNA. This method was based on the re-hybridization of DNA target with a recovery DNA to free the DNA probe. Functionalized silicon nanowire field-effect transistor (SiNW FET) was demonstrated to monitor such specific DNA-DNA interaction using high pathogenic strain virus hemagglutinin 1 (H1) DNA of avian influenza (AI) as target. Specific electric changes were observed in real-time for AI virus DNA sensing and device recovery when nanowire surface of SiNW FET was modified with complementary captured DNA probe. The recovery based SiNW FET biosensor can be further developed for fast identification and further confirmation of a variety of influenza virus strains and other infectious diseases.

Importance of limiting hohlraum leaks at cryogenic temperatures on NIF targets

DOE PAGES

Bhandarkar, Suhas; Teslich, Nick; Haid, Ben; ...

2017-08-18

Inertial confinement fusion targets are complex systems designed to allow fine control of temperature and pressure for making precise spherical ice layers of hydrogen isotopes at cryogenic temperatures. We discuss the various technical considerations for a maximum leak rate based on heat load considerations. This maximum flow rate turns out to bemore » $$5\\times 10^{-6}$$ standard cc per second, which can be caused by an orifice less than half a micron in diameter. This makes the identification of the location and resolution of the leak a significant challenge. To illustrate this, we showcase one example of a peculiar failure mode that appeared suddenly but persisted whereby target production yield was severely lowered. Identification of the leak source and the root cause requires very careful analysis of multiple thermomechanical aspects to ensure that the end solution is indeed the right remedy and is robust.« less

Application of infrared uncooled cameras in surveillance systems

NASA Astrophysics Data System (ADS)

Dulski, R.; Bareła, J.; Trzaskawka, P.; PiÄ tkowski, T.

2013-10-01

The recent necessity to protect military bases, convoys and patrols gave serious impact to the development of multisensor security systems for perimeter protection. One of the most important devices used in such systems are IR cameras. The paper discusses technical possibilities and limitations to use uncooled IR camera in a multi-sensor surveillance system for perimeter protection. Effective ranges of detection depend on the class of the sensor used and the observed scene itself. Application of IR camera increases the probability of intruder detection regardless of the time of day or weather conditions. It also simultaneously decreased the false alarm rate produced by the surveillance system. The role of IR cameras in the system was discussed as well as technical possibilities to detect human being. Comparison of commercially available IR cameras, capable to achieve desired ranges was done. The required spatial resolution for detection, recognition and identification was calculated. The simulation of detection ranges was done using a new model for predicting target acquisition performance which uses the Targeting Task Performance (TTP) metric. Like its predecessor, the Johnson criteria, the new model bounds the range performance with image quality. The scope of presented analysis is limited to the estimation of detection, recognition and identification ranges for typical thermal cameras with uncooled microbolometer focal plane arrays. This type of cameras is most widely used in security systems because of competitive price to performance ratio. Detection, recognition and identification range calculations were made, and the appropriate results for the devices with selected technical specifications were compared and discussed.

An enhanced targeted identification strategy for the selective identification of flavonoid O-glycosides from Carthamus tinctorius by integrating offline two-dimensional liquid chromatography/linear ion-trap-Orbitrap mass spectrometry, high-resolution diagnostic product ions/neutral loss filtering and liquid chromatography-solid phase extraction-nuclear magnetic resonance.

PubMed

Yao, Chang-Liang; Yang, Wen-Zhi; Si, Wei; Shen, Yao; Zhang, Nai-Xia; Chen, Hua-Li; Pan, Hui-Qin; Yang, Min; Wu, Wan-Ying; Guo, De-An

2017-03-31

Targeted identification of potentially bioactive molecules from herbal medicines is often stymied by the insufficient chromatographic separation, ubiquitous matrix interference, and pervasive isomerism. An enhanced targeted identification strategy is presented and validated by the selective identification of flavonoid O-glycosides (FOGs) from Carthamus tinctorius. It consists of four steps: (i) enhanced separation and detection by offline two-dimensional liquid chromatography/LTQ-Orbitrap MS (offline 2D-LC/LTQ-Orbitrap MS) using collision-induced dissociation (CID) and high-energy C-trap dissociation (HCD); (ii) improved identification of the major aglycones by acid hydrolysis and LC-SPE-NMR; (iii) simplified spectral elucidation by high-resolution diagnostic product ions/neutral loss filtering; and (iv) more convincing structural identification by matching an in-house library. An offline 2D-LC system configuring an Acchrom XAmide column and a BEH Shield RP-18 UPLC ® column enabled much better separation of the easily co-eluting components. Combined use of CID and HCD could produce complementary fragmentation information. The intensity ratios of the aglycone ion species ([Y 0 -H] - /Y 0 - and [Y 0 -2H] - /Y 0 - ) in the HCD-MS 2 spectra were found diagnostic for discriminating the aglycone subtypes and characterizing the glycosylation patterns. Five aglycone structures (kaempferol, 6-hydroxykaempferol, 6-methoxykaempferol, carthamidin, and isocarthamidin) were identified based on the 1 H-NMR data recorded by LC-SPE-NMR. Of the 107 characterized flavonoids, 80 FOGs were first reported from C. tinctorius. Unknown aglycones, pentose, and novel acyl substituents were discovered. A new compound thereof was isolated and fully identified, which could partially validate the MS-oriented identification. This integral strategy can improve the potency, efficiency, and accuracy in the detection of new compounds from medicinal herbs and other natural sources. Copyright © 2017 Elsevier B.V. All rights reserved.

Does methodology matter in eyewitness identification research? The effect of live versus video exposure on eyewitness identification accuracy.

PubMed

Pozzulo, Joanna D; Crescini, Charmagne; Panton, Tasha

2008-01-01

The present study examined the effect of mode of target exposure (live versus video) on eyewitness identification accuracy. Adult participants (N=104) were exposed to a staged crime that they witnessed either live or on videotape. Participants were then asked to rate their stress and arousal levels prior to being presented with either a target-present or -absent simultaneous lineup. Across target-present and -absent lineups, mode of target exposure did not have a significant effect on identification accuracy. However, mode of target exposure was found to have a significant effect on stress and arousal levels. Participants who witnessed the crime live had higher levels of stress and arousal than those who were exposed to the videotaped crime. A higher level of arousal was significantly related to poorer identification accuracy for those in the video condition. For participants in the live condition however, stress and arousal had no effect on eyewitness identification accuracy. Implications of these findings in regards to the generalizability of laboratory-based research on eyewitness testimony to real-life crime are discussed.

Systems genetics for drug target discovery

PubMed Central

Penrod, Nadia M.; Cowper-Sal_lari, Richard; Moore, Jason H.

2011-01-01

The collection and analysis of genomic data has the potential to reveal novel druggable targets by providing insight into the genetic basis of disease. However, the number of drugs, targeting new molecular entities, approved by the US Food and Drug Administration (FDA) has not increased in the years since the collection of genomic data has become commonplace. The paucity of translatable results can be partly attributed to conventional analysis methods that test one gene at a time in an effort to identify disease-associated factors as candidate drug targets. By disengaging genetic factors from their position within the genetic regulatory system, much of the information stored within the genomic data set is lost. Here we discuss how genomic data is used to identify disease-associated genes or genomic regions, how disease-associated regions are validated as functional targets, and the role network analysis can play in bridging the gap between data generation and effective drug target identification. PMID:21862141

Gene silencing in Tribolium castaneum as a tool for the targeted identification of candidate RNAi targets in crop pests.

PubMed

Knorr, Eileen; Fishilevich, Elane; Tenbusch, Linda; Frey, Meghan L F; Rangasamy, Murugesan; Billion, Andre; Worden, Sarah E; Gandra, Premchand; Arora, Kanika; Lo, Wendy; Schulenberg, Greg; Valverde-Garcia, Pablo; Vilcinskas, Andreas; Narva, Kenneth E

2018-02-01

RNAi shows potential as an agricultural technology for insect control, yet, a relatively low number of robust lethal RNAi targets have been demonstrated to control insects of agricultural interest. In the current study, a selection of lethal RNAi target genes from the iBeetle (Tribolium castaneum) screen were used to demonstrate efficacy of orthologous targets in the economically important coleopteran pests Diabrotica virgifera virgifera and Meligethes aeneus. Transcript orthologs of 50 selected genes were analyzed in D. v. virgifera diet-based RNAi bioassays; 21 of these RNAi targets showed mortality and 36 showed growth inhibition. Low dose injection- and diet-based dsRNA assays in T. castaneum and D. v. virgifera, respectively, enabled the identification of the four highly potent RNAi target genes: Rop, dre4, ncm, and RpII140. Maize was genetically engineered to express dsRNA directed against these prioritized candidate target genes. T 0 plants expressing Rop, dre4, or RpII140 RNA hairpins showed protection from D. v. virgifera larval feeding damage. dsRNA targeting Rop, dre4, ncm, and RpII140 in M. aeneus also caused high levels of mortality both by injection and feeding. In summary, high throughput systems for model organisms can be successfully used to identify potent RNA targets for difficult-to-work with agricultural insect pests.

Automated target recognition using passive radar and coordinated flight models

NASA Astrophysics Data System (ADS)

Ehrman, Lisa M.; Lanterman, Aaron D.

2003-09-01

Rather than emitting pulses, passive radar systems rely on illuminators of opportunity, such as TV and FM radio, to illuminate potential targets. These systems are particularly attractive since they allow receivers to operate without emitting energy, rendering them covert. Many existing passive radar systems estimate the locations and velocities of targets. This paper focuses on adding an automatic target recognition (ATR) component to such systems. Our approach to ATR compares the Radar Cross Section (RCS) of targets detected by a passive radar system to the simulated RCS of known targets. To make the comparison as accurate as possible, the received signal model accounts for aircraft position and orientation, propagation losses, and antenna gain patterns. The estimated positions become inputs for an algorithm that uses a coordinated flight model to compute probable aircraft orientation angles. The Fast Illinois Solver Code (FISC) simulates the RCS of several potential target classes as they execute the estimated maneuvers. The RCS is then scaled by the Advanced Refractive Effects Prediction System (AREPS) code to account for propagation losses that occur as functions of altitude and range. The Numerical Electromagnetic Code (NEC2) computes the antenna gain pattern, so that the RCS can be further scaled. The Rician model compares the RCS of the illuminated aircraft with those of the potential targets. This comparison results in target identification.

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

PubMed

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

2016-12-01

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

Construction of a directed hammerhead ribozyme library: towards the identification of optimal target sites for antisense-mediated gene inhibition.

PubMed Central

Pierce, M L; Ruffner, D E

1998-01-01

Antisense-mediated gene inhibition uses short complementary DNA or RNA oligonucleotides to block expression of any mRNA of interest. A key parameter in the success or failure of an antisense therapy is the identification of a suitable target site on the chosen mRNA. Ultimately, the accessibility of the target to the antisense agent determines target suitability. Since accessibility is a function of many complex factors, it is currently beyond our ability to predict. Consequently, identification of the most effective target(s) requires examination of every site. Towards this goal, we describe a method to construct directed ribozyme libraries against any chosen mRNA. The library contains nearly equal amounts of ribozymes targeting every site on the chosen transcript and the library only contains ribozymes capable of binding to that transcript. Expression of the ribozyme library in cultured cells should allow identification of optimal target sites under natural conditions, subject to the complexities of a fully functional cell. Optimal target sites identified in this manner should be the most effective sites for therapeutic intervention. PMID:9801305

We Turned to Madison Avenue for Tips on Selling Our $64 Million Bond Issue.

ERIC Educational Resources Information Center

Conyers, John G.; Francl, Terry

1989-01-01

An Illinois school system won a bond issue election with a 30-day marketing campaign. Helpful marketing practices include identification of the target audience and finding the best medium to reach the audience. (MLF)

GEPSI: A Gene Expression Profile Similarity-Based Identification Method of Bioactive Components in Traditional Chinese Medicine Formula.

PubMed

Zhang, Baixia; He, Shuaibing; Lv, Chenyang; Zhang, Yanling; Wang, Yun

2018-01-01

The identification of bioactive components in traditional Chinese medicine (TCM) is an important part of the TCM material foundation research. Recently, molecular docking technology has been extensively used for the identification of TCM bioactive components. However, target proteins that are used in molecular docking may not be the actual TCM target. For this reason, the bioactive components would likely be omitted or incorrect. To address this problem, this study proposed the GEPSI method that identified the target proteins of TCM based on the similarity of gene expression profiles. The similarity of the gene expression profiles affected by TCM and small molecular drugs was calculated. The pharmacological action of TCM may be similar to that of small molecule drugs that have a high similarity score. Indeed, the target proteins of the small molecule drugs could be considered TCM targets. Thus, we identified the bioactive components of a TCM by molecular docking and verified the reliability of this method by a literature investigation. Using the target proteins that TCM actually affected as targets, the identification of the bioactive components was more accurate. This study provides a fast and effective method for the identification of TCM bioactive components.

GEPSI: A Gene Expression Profile Similarity-Based Identification Method of Bioactive Components in Traditional Chinese Medicine Formula

PubMed Central

Zhang, Baixia; He, Shuaibing; Lv, Chenyang; Zhang, Yanling

2018-01-01

The identification of bioactive components in traditional Chinese medicine (TCM) is an important part of the TCM material foundation research. Recently, molecular docking technology has been extensively used for the identification of TCM bioactive components. However, target proteins that are used in molecular docking may not be the actual TCM target. For this reason, the bioactive components would likely be omitted or incorrect. To address this problem, this study proposed the GEPSI method that identified the target proteins of TCM based on the similarity of gene expression profiles. The similarity of the gene expression profiles affected by TCM and small molecular drugs was calculated. The pharmacological action of TCM may be similar to that of small molecule drugs that have a high similarity score. Indeed, the target proteins of the small molecule drugs could be considered TCM targets. Thus, we identified the bioactive components of a TCM by molecular docking and verified the reliability of this method by a literature investigation. Using the target proteins that TCM actually affected as targets, the identification of the bioactive components was more accurate. This study provides a fast and effective method for the identification of TCM bioactive components. PMID:29692857

Application of targeted quantitative proteomics analysis in human cerebrospinal fluid using a liquid chromatography matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (LC MALDI TOF/TOF) platform.

PubMed

Pan, Sheng; Rush, John; Peskind, Elaine R; Galasko, Douglas; Chung, Kathryn; Quinn, Joseph; Jankovic, Joseph; Leverenz, James B; Zabetian, Cyrus; Pan, Catherine; Wang, Yan; Oh, Jung Hun; Gao, Jean; Zhang, Jianpeng; Montine, Thomas; Zhang, Jing

2008-02-01

Targeted quantitative proteomics by mass spectrometry aims to selectively detect one or a panel of peptides/proteins in a complex sample and is particularly appealing for novel biomarker verification/validation because it does not require specific antibodies. Here, we demonstrated the application of targeted quantitative proteomics in searching, identifying, and quantifying selected peptides in human cerebrospinal spinal fluid (CSF) using a matrix-assisted laser desorption/ionization time-of-flight tandem mass spectrometer (MALDI TOF/TOF)-based platform. The approach involved two major components: the use of isotopic-labeled synthetic peptides as references for targeted identification and quantification and a highly selective mass spectrometric analysis based on the unique characteristics of the MALDI instrument. The platform provides high confidence for targeted peptide detection in a complex system and can potentially be developed into a high-throughput system. Using the liquid chromatography (LC) MALDI TOF/TOF platform and the complementary identification strategy, we were able to selectively identify and quantify a panel of targeted peptides in the whole proteome of CSF without prior depletion of abundant proteins. The effectiveness and robustness of the approach associated with different sample complexity, sample preparation strategies, as well as mass spectrometric quantification were evaluated. Other issues related to chromatography separation and the feasibility for high-throughput analysis were also discussed. Finally, we applied targeted quantitative proteomics to analyze a subset of previously identified candidate markers in CSF samples of patients with Parkinson's disease (PD) at different stages and Alzheimer's disease (AD) along with normal controls.

Direct Quantification of Methane Emissions Across the Supply Chain: Identification of Mitigation Targets

NASA Astrophysics Data System (ADS)

Darzi, M.; Johnson, D.; Heltzel, R.; Clark, N.

2017-12-01

Researchers at West Virginia University's Center for Alternative Fuels, Engines, and Emissions have recently participated in a variety of studies targeted at direction quantification of methane emissions from across the natural gas supply chain. These studies included assessing methane emissions from heavy-duty vehicles and their fuel stations, active unconventional well sites - during both development and production, natural gas compression and storage facilities, natural gas engines - both large and small, two- and four-stroke, and low-throughput equipment associated with coal bed methane wells. Engine emissions were sampled using conventional instruments such as Fourier transform infrared spectrometers and heated flame ionization detection analyzers. However, to accurately quantify a wide range of other sources beyond the tailpipe (both leaks and losses), a full flow sampling system was developed, which included an integrated cavity-enhanced absorption spectrometer. Through these direct quantification efforts and analysis major sources of methane emissions were identified. Technological solutions and best practices exist or could be developed to reduce methane emissions by focusing on the "lowest-hanging fruit." For example, engine crankcases from across the supply chain should employ vent mitigation systems to reduce methane and other emissions. An overview of the direct quantification system and various campaign measurements results will be presented along with the identification of other targets for additional mitigation.

IDENTIFICATION OF ACTIVE BACTERIAL COMMUNITIES IN A MODEL DRINKING WATER BIOFILM SYSTEM USING 16S RRNA-BASED CLONE LIBRARIES

EPA Science Inventory

Recent phylogenetic studies have used DNA as the target molecule for the development of environmental 16S rDNA clone libraries. As DNA may persist in the environment, DNA-based libraries cannot be used to identify metabolically active bacteria in water systems. In this study, a...

Molecular prey identification in Central European piscivores.

PubMed

Thalinger, Bettina; Oehm, Johannes; Mayr, Hannes; Obwexer, Armin; Zeisler, Christiane; Traugott, Michael

2016-01-01

Diet analysis is an important aspect when investigating the ecology of fish-eating animals and essential for assessing their functional role in food webs across aquatic and terrestrial ecosystems. The identification of fish remains in dietary samples, however, can be time-consuming and unsatisfying using conventional morphological analysis of prey remains. Here, we present a two-step multiplex PCR system, comprised of six assays, allowing for rapid, sensitive and specific detection of fish DNA in dietary samples. This approach encompasses 78 fish and lamprey species native to Central European freshwaters and enables the identification of 31 species, six genera, two families, two orders and two fish family clusters. All targeted taxa were successfully amplified from 25 template molecules, and each assay was specific when tested against a wide range of invertebrates and vertebrates inhabiting aquatic environments. The applicability of the multiplex PCR system was evaluated in a feeding trial, wherein it outperformed morphological prey analysis regarding species-specific prey identification in faeces of Eurasian otters. Additionally, a wide spectrum of fish species was detected in field-collected faecal samples and regurgitated pellets of Common Kingfishers and Great Cormorants, demonstrating the broad applicability of the approach. In conclusion, this multiplex PCR system provides an efficient, easy to use and cost-effective tool for assessing the trophic ecology of piscivores in Central Europe. Furthermore, the multiplex PCRs and the primers described therein will be applicable wherever DNA of the targeted fish species needs to be detected at high sensitivity and specificity. © 2015 The Authors. Molecular Ecology Resources Published by John Wiley & Sons Ltd.

Autonomous target recognition using remotely sensed surface vibration measurements

NASA Astrophysics Data System (ADS)

Geurts, James; Ruck, Dennis W.; Rogers, Steven K.; Oxley, Mark E.; Barr, Dallas N.

1993-09-01

The remotely measured surface vibration signatures of tactical military ground vehicles are investigated for use in target classification and identification friend or foe (IFF) systems. The use of remote surface vibration sensing by a laser radar reduces the effects of partial occlusion, concealment, and camouflage experienced by automatic target recognition systems using traditional imagery in a tactical battlefield environment. Linear Predictive Coding (LPC) efficiently represents the vibration signatures and nearest neighbor classifiers exploit the LPC feature set using a variety of distortion metrics. Nearest neighbor classifiers achieve an 88 percent classification rate in an eight class problem, representing a classification performance increase of thirty percent from previous efforts. A novel confidence figure of merit is implemented to attain a 100 percent classification rate with less than 60 percent rejection. The high classification rates are achieved on a target set which would pose significant problems to traditional image-based recognition systems. The targets are presented to the sensor in a variety of aspects and engine speeds at a range of 1 kilometer. The classification rates achieved demonstrate the benefits of using remote vibration measurement in a ground IFF system. The signature modeling and classification system can also be used to identify rotary and fixed-wing targets.

Discovery of Nigri/nox and Panto/pox site-specific recombinase systems facilitates advanced genome engineering

PubMed Central

Karimova, Madina; Splith, Victoria; Karpinski, Janet; Pisabarro, M. Teresa; Buchholz, Frank

2016-01-01

Precise genome engineering is instrumental for biomedical research and holds great promise for future therapeutic applications. Site-specific recombinases (SSRs) are valuable tools for genome engineering due to their exceptional ability to mediate precise excision, integration and inversion of genomic DNA in living systems. The ever-increasing complexity of genome manipulations and the desire to understand the DNA-binding specificity of these enzymes are driving efforts to identify novel SSR systems with unique properties. Here, we describe two novel tyrosine site-specific recombination systems designated Nigri/nox and Panto/pox. Nigri originates from Vibrio nigripulchritudo (plasmid VIBNI_pA) and recombines its target site nox with high efficiency and high target-site selectivity, without recombining target sites of the well established SSRs Cre, Dre, Vika and VCre. Panto, derived from Pantoea sp. aB, is less specific and in addition to its native target site, pox also recombines the target site for Dre recombinase, called rox. This relaxed specificity allowed the identification of residues that are involved in target site selectivity, thereby advancing our understanding of how SSRs recognize their respective DNA targets. PMID:27444945

A novel neural network based image reconstruction model with scale and rotation invariance for target identification and classification for Active millimetre wave imaging

NASA Astrophysics Data System (ADS)

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.

Identification and modeling of the electrohydraulic systems of the main gun of a main battle tank

NASA Astrophysics Data System (ADS)

Campos, Luiz C. A.; Menegaldo, Luciano L.

2012-11-01

The black-box mathematical models of the electrohydraulic systems responsible for driving the two degrees of freedom (elevation and azimuth) of the main gun of a main battle tank (MBT) were identified. Such systems respond to gunner's inputs while acquiring and tracking targets. Identification experiments were designed to collect simultaneous data from two inertial measurement units (IMU) installed at the gunner's handle (input) and at the center of rotation of the turret (output), for the identification of the azimuth system. For the elevation system, IMUs were installed at the gunner's handle (input) and at the breech of the gun (output). Linear accelerations and angular rates were collected for both input and output. Several black-box model architectures were investigated. As a result, nonlinear autoregressive with exogenous variables (NARX) second order model and nonlinear finite impulse response (NFIR) fourth order model, demonstrate to best fit the experimental data, with low computational costs. The derived models are being employed in a broader research, aiming to reproduce such systems in a laboratory virtual main gun simulator.

Predictive teratology: teratogenic risk-hazard identification partnered in the discovery process.

PubMed

Augustine-Rauch, K A

2008-11-01

Unexpected teratogenicity is ranked as one of the most prevalent causes for toxicity-related attrition of drug candidates. Without proactive assessment, the liability tends to be identified relatively late in drug development, following significant investment in compound and engagement in pre clinical and clinical studies. When unexpected teratogenicity occurs in pre-clinical development, three principle questions arise: Can clinical trials that include women of child bearing populations be initiated? Will all compounds in this pharmacological class produce the same liability? Could this effect be related to the chemical structure resulting in undesirable off-target adverse effects? The first question is typically addressed at the time of the unexpected finding and involves considering the nature of the teratogenicity, whether or not maternal toxicity could have had a role in onset, human exposure margins and therapeutic indication. The latter two questions can be addressed proactively, earlier in the discovery process as drug target profiling and lead compound optimization is taking place. Such proactive approaches include thorough assessment of the literature for identification of potential liabilities and follow-up work that can be conducted on the level of target expression and functional characterization using molecular biology and developmental model systems. Developmental model systems can also be applied in the form of in vitro teratogenicity screens, and show potential for effective hazard identification or issue resolution on the level of characterizing teratogenic mechanism. This review discusses approaches that can be applied for proactive assessment of compounds for teratogenic liability.

A Supplementary Clear-Sky Snow and Ice Recognition Technique for CERES Level 2 Products

NASA Technical Reports Server (NTRS)

Radkevich, Alexander; Khlopenkov, Konstantin; Rutan, David; Kato, Seiji

2013-01-01

Identification of clear-sky snow and ice is an important step in the production of cryosphere radiation budget products, which are used in the derivation of long-term data series for climate research. In this paper, a new method of clear-sky snow/ice identification for Moderate Resolution Imaging Spectroradiometer (MODIS) is presented. The algorithm's goal is to enhance the identification of snow and ice within the Clouds and the Earth's Radiant Energy System (CERES) data after application of the standard CERES scene identification scheme. The input of the algorithm uses spectral radiances from five MODIS bands and surface skin temperature available in the CERES Single Scanner Footprint (SSF) product. The algorithm produces a cryosphere rating from an aggregated test: a higher rating corresponds to a more certain identification of the clear-sky snow/ice-covered scene. Empirical analysis of regions of interest representing distinctive targets such as snow, ice, ice and water clouds, open waters, and snow-free land selected from a number of MODIS images shows that the cryosphere rating of snow/ice targets falls into 95% confidence intervals lying above the same confidence intervals of all other targets. This enables recognition of clear-sky cryosphere by using a single threshold applied to the rating, which makes this technique different from traditional branching techniques based on multiple thresholds. Limited tests show that the established threshold clearly separates the cryosphere rating values computed for the cryosphere from those computed for noncryosphere scenes, whereas individual tests applied consequently cannot reliably identify the cryosphere for complex scenes.

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

PubMed

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. Copyright © 2014 The Authors. Published by Elsevier Inc. All rights reserved.

Historeceptomic Fingerprints for Drug-Like Compounds.

PubMed

Shmelkov, Evgeny; Grigoryan, Arsen; Swetnam, James; Xin, Junyang; Tivon, Doreen; Shmelkov, Sergey V; Cardozo, Timothy

2015-01-01

Most drugs exert their beneficial and adverse effects through their combined action on several different molecular targets (polypharmacology). The true molecular fingerprint of the direct action of a drug has two components: the ensemble of all the receptors upon which a drug acts and their level of expression in organs/tissues. Conversely, the fingerprint of the adverse effects of a drug may derive from its action in bystander tissues. The ensemble of targets is almost always only partially known. Here we describe an approach improving upon and integrating both components: in silico identification of a more comprehensive ensemble of targets for any drug weighted by the expression of those receptors in relevant tissues. Our system combines more than 300,000 experimentally determined bioactivity values from the ChEMBL database and 4.2 billion molecular docking scores. We integrated these scores with gene expression data for human receptors across a panel of human tissues to produce drug-specific tissue-receptor (historeceptomics) scores. A statistical model was designed to identify significant scores, which define an improved fingerprint representing the unique activity of any drug. These multi-dimensional historeceptomic fingerprints describe, in a novel, intuitive, and easy to interpret style, the holistic, in vivo picture of the mechanism of any drug's action. Valuable applications in drug discovery and personalized medicine, including the identification of molecular signatures for drugs with polypharmacologic modes of action, detection of tissue-specific adverse effects of drugs, matching molecular signatures of a disease to drugs, target identification for bioactive compounds with unknown receptors, and hypothesis generation for drug/compound phenotypes may be enabled by this approach. The system has been deployed at drugable.org for access through a user-friendly web site.

Clinical implications of omics and systems medicine: focus on predictive and individualized treatment.

PubMed

Benson, M

2016-03-01

Many patients with common diseases do not respond to treatment. This is a key challenge to modern health care, which causes both suffering and enormous costs. One important reason for the lack of treatment response is that common diseases are associated with altered interactions between thousands of genes, in combinations that differ between subgroups of patients who do or do not respond to a given treatment. Such subgroups, or even distinct disease entities, have been described recently in asthma, diabetes, autoimmune diseases and cancer. High-throughput techniques (omics) allow identification and characterization of such subgroups or entities. This may have important clinical implications, such as identification of diagnostic markers for individualized medicine, as well as new therapeutic targets for patients who do not respond to existing drugs. For example, whole-genome sequencing may be applied to more accurately guide treatment of neurodevelopmental diseases, or to identify drugs specifically targeting mutated genes in cancer. A study published in 2015 showed that 28% of hepatocellular carcinomas contained mutated genes that potentially could be targeted by drugs already approved by the US Food and Drug Administration. A translational study, which is described in detail, showed how combined omics, computational, functional and clinical studies could identify and validate a novel diagnostic and therapeutic candidate gene in allergy. Another important clinical implication is the identification of potential diagnostic markers and therapeutic targets for predictive and preventative medicine. By combining computational and experimental methods, early disease regulators may be identified and potentially used to predict and treat disease before it becomes symptomatic. Systems medicine is an emerging discipline, which may contribute to such developments through combining omics with computational, functional and clinical studies. The aims of this review are to provide a brief introduction to systems medicine and discuss how it may contribute to the clinical implementation of individualized treatment, using clinically relevant examples. © 2015 The Association for the Publication of the Journal of Internal Medicine.

Constraints in distortion-invariant target recognition system simulation

NASA Astrophysics Data System (ADS)

Iftekharuddin, Khan M.; Razzaque, Md A.

2000-11-01

Automatic target recognition (ATR) is a mature but active research area. In an earlier paper, we proposed a novel ATR approach for recognition of targets varying in fine details, rotation, and translation using a Learning Vector Quantization (LVQ) Neural Network (NN). The proposed approach performed segmentation of multiple objects and the identification of the objects using LVQNN. In this current paper, we extend the previous approach for recognition of targets varying in rotation, translation, scale, and combination of all three distortions. We obtain the analytical results of the system level design to show that the approach performs well with some constraints. The first constraint determines the size of the input images and input filters. The second constraint shows the limits on amount of rotation, translation, and scale of input objects. We present the simulation verification of the constraints using DARPA's Moving and Stationary Target Recognition (MSTAR) images with different depression and pose angles. The simulation results using MSTAR images verify the analytical constraints of the system level design.

Identification and Validation of Ifit1 as an Important Innate Immune Bottleneck

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, Jason E.; Vartanian, Keri B.; Mitchell, Hugh D.

The innate immune system plays important roles in a number of disparate processes. Foremost, innate immunity is a first responder to invasion by pathogens and triggers early defensive responses and recruits the adaptive immune system. The innate immune system also responds to endogenous damage signals that arise from tissue injury. Recently it has been found that innate immunity plays an important role in neuroprotection against ischemic stroke through the activation of the primary innate immune receptors, Toll-like receptors (TLRs). Using several large-scale transcriptomic data sets from mouse and mouse macrophage studies we identified targets predicted to be important in controllingmore » innate immune processes initiated by TLR activation. Targets were identified as genes with high betweenness centrality, so-called bottlenecks, in networks inferred from statistical associations between gene expression patterns. A small set of putative bottlenecks were identified in each of the data sets investigated including interferon-stimulated genes (Ifit1, Ifi47, Tgtp and Oasl2) as well as genes uncharacterized in immune responses (Axud1 and Ppp1r15a). We further validated one of these targets, Ifit1, in mouse macrophages by showing that silencing it suppresses induction of predicted downstream genes by lipopolysaccharide (LPS)-mediated TLR4 activation through an unknown direct or indirect mechanism. Our study demonstrates the utility of network analysis for identification of interesting targets related to innate immune function, and highlights that Ifit1 can exert a positive regulatory effect on downstream genes.« less

Implantable radio frequency identification sensors: wireless power and communication.

PubMed

Hutchens, Chriswell; Rennaker, Robert L; Venkataraman, Srinivasan; Ahmed, Rehan; Liao, Ran; Ibrahim, Tamer

2011-01-01

There are significant technical challenges in the development of a fully implantable wirelessly powered neural interface. Challenges include wireless transmission of sufficient power to the implanted device to ensure reliable operation for decades without replacement, minimizing tissue heating, and adequate reliable communications bandwidth. Overcoming these challenges is essential for the development of implantable closed loop system for the treatment of disorders ranging from epilepsy, incontinence, stroke and spinal cord injury. We discuss the development of the wireless power, communication and control for a Radio-Frequency Identification Sensor (RFIDS) system with targeted power range for a 700 mV, 30 to 40 uA load attained at -2 dBm.

Automated identification of molecular effects of drugs (AIMED)

PubMed Central

Fathiamini, Safa; Johnson, Amber M; Zeng, Jia; Araya, Alejandro; Holla, Vijaykumar; Bailey, Ann M; Litzenburger, Beate C; Sanchez, Nora S; Khotskaya, Yekaterina; Xu, Hua; Meric-Bernstam, Funda; Bernstam, Elmer V

2016-01-01

Introduction Genomic profiling information is frequently available to oncologists, enabling targeted cancer therapy. Because clinically relevant information is rapidly emerging in the literature and elsewhere, there is a need for informatics technologies to support targeted therapies. To this end, we have developed a system for Automated Identification of Molecular Effects of Drugs, to help biomedical scientists curate this literature to facilitate decision support. Objectives To create an automated system to identify assertions in the literature concerning drugs targeting genes with therapeutic implications and characterize the challenges inherent in automating this process in rapidly evolving domains. Methods We used subject-predicate-object triples (semantic predications) and co-occurrence relations generated by applying the SemRep Natural Language Processing system to MEDLINE abstracts and ClinicalTrials.gov descriptions. We applied customized semantic queries to find drugs targeting genes of interest. The results were manually reviewed by a team of experts. Results Compared to a manually curated set of relationships, recall, precision, and F2 were 0.39, 0.21, and 0.33, respectively, which represents a 3- to 4-fold improvement over a publically available set of predications (SemMedDB) alone. Upon review of ostensibly false positive results, 26% were considered relevant additions to the reference set, and an additional 61% were considered to be relevant for review. Adding co-occurrence data improved results for drugs in early development, but not their better-established counterparts. Conclusions Precision medicine poses unique challenges for biomedical informatics systems that help domain experts find answers to their research questions. Further research is required to improve the performance of such systems, particularly for drugs in development. PMID:27107438

Sleep and eyewitness memory: Fewer false identifications after sleep when the target is absent from the lineup.

PubMed

Stepan, Michelle E; Dehnke, Taylor M; Fenn, Kimberly M

2017-01-01

Inaccurate eyewitness identifications are the leading cause of known false convictions in the United States. Moreover, improving eyewitness memory is difficult and often unsuccessful. Sleep consistently strengthens and protects memory from interference, particularly when a recall test is used. However, the effect of sleep on recognition memory is more equivocal. Eyewitness identification tests are often recognition based, thus leaving open the question of how sleep affects recognition performance in an eyewitness context. In the current study, we investigated the effect of sleep on eyewitness memory. Participants watched a video of a mock-crime and attempted to identify the perpetrator from a simultaneous lineup after a 12-hour retention interval that either spanned a waking day or night of sleep. In Experiment 1, we used a target-present lineup and, in Experiment 2, we used a target-absent lineup in order to investigate correct and false identifications, respectively. Sleep reduced false identifications in the target-absent lineup (Experiment 2) but had no effect on correct identifications in the target-present lineup (Experiment 1). These results are discussed with respect to memory strength and decision making strategies.

Sleep and eyewitness memory: Fewer false identifications after sleep when the target is absent from the lineup

PubMed Central

Dehnke, Taylor M.; Fenn, Kimberly M.

2017-01-01

Inaccurate eyewitness identifications are the leading cause of known false convictions in the United States. Moreover, improving eyewitness memory is difficult and often unsuccessful. Sleep consistently strengthens and protects memory from interference, particularly when a recall test is used. However, the effect of sleep on recognition memory is more equivocal. Eyewitness identification tests are often recognition based, thus leaving open the question of how sleep affects recognition performance in an eyewitness context. In the current study, we investigated the effect of sleep on eyewitness memory. Participants watched a video of a mock-crime and attempted to identify the perpetrator from a simultaneous lineup after a 12-hour retention interval that either spanned a waking day or night of sleep. In Experiment 1, we used a target-present lineup and, in Experiment 2, we used a target-absent lineup in order to investigate correct and false identifications, respectively. Sleep reduced false identifications in the target-absent lineup (Experiment 2) but had no effect on correct identifications in the target-present lineup (Experiment 1). These results are discussed with respect to memory strength and decision making strategies. PMID:28877169

Near-Field Chipless Radio-Frequency Identification (RFID) Sensing and Identification System with Switching Reading.

PubMed

Paredes, Ferran; Herrojo, Cristian; Mata-Contreras, Javier; Moras, Miquel; Núñez, Alba; Ramon, Eloi; Martín, Ferran

2018-04-09

A chipless radio-frequency identification (chipless-RFID) and sensing system, where tags are read by proximity (near-field) through a switch, is presented. The tags consist of a set of identical resonant elements (split-ring resonators or SRRs), printed or etched at predefined and equidistant positions, forming a linear chain, each SRR providing a bit of information. The logic state ('1' or '0') associated with each resonator depends on whether it is present or not in the predefined position. The reader is an array of power splitters used to feed a set of SRR-loaded transmission lines (in equal number to the number of resonant elements, or bits, of the tag). The feeding (interrogation) signal is a harmonic (single-tone) signal tuned to a frequency in the vicinity of the fundamental resonance of the SRRs. The set of SRR-loaded lines must be designed so that the corresponding SRRs are in perfect alignment with the SRRs of the tag, provided the tag is positioned on top of the reader. Thus, in a reading operation, as long as the tag is very close to the reader, the SRRs of the tag modify (decrease) the transmission coefficient of the corresponding reader line (through electromagnetic coupling between both SRRs), and the amplitude of the output signal is severely reduced. Therefore, the identification (ID) code of the tag is contained in the amplitudes of the output signals of the SRR-loaded lines, which can be inferred sequentially by means of a switching system. Unlike previous chipless-RFID systems based on near-field and sequential bit reading, the tags in the proposed system can be merely positioned on top of the reader, conveniently aligned, without the need to mechanically place them across the reader. Since tag reading is only possible if the tag is very close to the reader, this system can be also used as a proximity sensor with applications such as target identification. The proposed chipless-RFID and sensing approach is validated by reading a designed 4-bit tag. For identification purposes, this system is of special interest in applications where a low number of bits suffice, and tag reading by proximity is acceptable (or even convenient). Applications mostly related to secure paper, particularly involving a limited number of items (e.g., exams, ballots, etc.), in order to provide authenticity and avoid counterfeiting, are envisaged. As a proximity sensor, the system may be of use in detecting and distinguishing different targets in applications such as smart packaging.

Near-Field Chipless Radio-Frequency Identification (RFID) Sensing and Identification System with Switching Reading

PubMed Central

Mata-Contreras, Javier; Moras, Miquel; Ramon, Eloi; Martín, Ferran

2018-01-01

A chipless radio-frequency identification (chipless-RFID) and sensing system, where tags are read by proximity (near-field) through a switch, is presented. The tags consist of a set of identical resonant elements (split-ring resonators or SRRs), printed or etched at predefined and equidistant positions, forming a linear chain, each SRR providing a bit of information. The logic state (‘1’ or ‘0’) associated with each resonator depends on whether it is present or not in the predefined position. The reader is an array of power splitters used to feed a set of SRR-loaded transmission lines (in equal number to the number of resonant elements, or bits, of the tag). The feeding (interrogation) signal is a harmonic (single-tone) signal tuned to a frequency in the vicinity of the fundamental resonance of the SRRs. The set of SRR-loaded lines must be designed so that the corresponding SRRs are in perfect alignment with the SRRs of the tag, provided the tag is positioned on top of the reader. Thus, in a reading operation, as long as the tag is very close to the reader, the SRRs of the tag modify (decrease) the transmission coefficient of the corresponding reader line (through electromagnetic coupling between both SRRs), and the amplitude of the output signal is severely reduced. Therefore, the identification (ID) code of the tag is contained in the amplitudes of the output signals of the SRR-loaded lines, which can be inferred sequentially by means of a switching system. Unlike previous chipless-RFID systems based on near-field and sequential bit reading, the tags in the proposed system can be merely positioned on top of the reader, conveniently aligned, without the need to mechanically place them across the reader. Since tag reading is only possible if the tag is very close to the reader, this system can be also used as a proximity sensor with applications such as target identification. The proposed chipless-RFID and sensing approach is validated by reading a designed 4-bit tag. For identification purposes, this system is of special interest in applications where a low number of bits suffice, and tag reading by proximity is acceptable (or even convenient). Applications mostly related to secure paper, particularly involving a limited number of items (e.g., exams, ballots, etc.), in order to provide authenticity and avoid counterfeiting, are envisaged. As a proximity sensor, the system may be of use in detecting and distinguishing different targets in applications such as smart packaging. PMID:29642560

Enhanced terahertz imaging system performance analysis and design tool for concealed weapon identification

NASA Astrophysics Data System (ADS)

Murrill, Steven R.; Franck, Charmaine C.; Espinola, Richard L.; Petkie, Douglas T.; De Lucia, Frank C.; Jacobs, Eddie L.

2011-11-01

The U.S. Army Research Laboratory (ARL) and the U.S. Army Night Vision and Electronic Sensors Directorate (NVESD) have developed a terahertz-band imaging system performance model/tool for detection and identification of concealed weaponry. The details of the MATLAB-based model which accounts for the effects of all critical sensor and display components, and for the effects of atmospheric attenuation, concealment material attenuation, and active illumination, were reported on at the 2005 SPIE Europe Security & Defence Symposium (Brugge). An advanced version of the base model that accounts for both the dramatic impact that target and background orientation can have on target observability as related to specular and Lambertian reflections captured by an active-illumination-based imaging system, and for the impact of target and background thermal emission, was reported on at the 2007 SPIE Defense and Security Symposium (Orlando). This paper will provide a comprehensive review of an enhanced, user-friendly, Windows-executable, terahertz-band imaging system performance analysis and design tool that now includes additional features such as a MODTRAN-based atmospheric attenuation calculator and advanced system architecture configuration inputs that allow for straightforward performance analysis of active or passive systems based on scanning (single- or line-array detector element(s)) or staring (focal-plane-array detector elements) imaging architectures. This newly enhanced THz imaging system design tool is an extension of the advanced THz imaging system performance model that was developed under the Defense Advanced Research Project Agency's (DARPA) Terahertz Imaging Focal-Plane Technology (TIFT) program. This paper will also provide example system component (active-illumination source and detector) trade-study analyses using the new features of this user-friendly THz imaging system performance analysis and design tool.

Background characterization techniques for target detection using scene metrics and pattern recognition

NASA Astrophysics Data System (ADS)

Noah, Paul V.; Noah, Meg A.; Schroeder, John W.; Chernick, Julian A.

1990-09-01

The U.S. Army has a requirement to develop systems for the detection and identification of ground targets in a clutter environment. Autonomous Homing Munitions (AHM) using infrared, visible, millimeter wave and other sensors are being investigated for this application. Advanced signal processing and computational approaches using pattern recognition and artificial intelligence techniques combined with multisensor data fusion have the potential to meet the Army's requirements for next generation ARM.

Identification of small-molecule antagonists of the Pseudomonas aeruginosa transcriptional regulator PqsR: biophysically guided hit discovery and optimization.

PubMed

Klein, Tobias; Henn, Claudia; de Jong, Johannes C; Zimmer, Christina; Kirsch, Benjamin; Maurer, Christine K; Pistorius, Dominik; Müller, Rolf; Steinbach, Anke; Hartmann, Rolf W

2012-09-21

The Gram-negative pathogen Pseudomonas aeruginosa produces an intercellular alkyl quinolone signaling molecule, the Pseudomonas quinolone signal. The pqs quorum sensing communication system that is characteristic for P. aeruginosa regulates the production of virulence factors. Therefore, we consider the pqs system a novel target to limit P. aeruginosa pathogenicity. Here, we present small molecules targeting a key player of the pqs system, PqsR. A rational design strategy in combination with surface plasmon resonance biosensor analysis led to the identification of PqsR binders. Determination of thermodynamic binding signatures and functional characterization in E. coli guided the hit optimization, resulting in the potent hydroxamic acid derived PqsR antagonist 11 (IC(50) = 12.5 μM). Remarkably it displayed a comparable potency in P. aeruginosa (IC(50) = 23.6 μM) and reduced the production of the virulence factor pyocyanin. Beyond this, site-directed mutagenesis together with thermodynamic analysis provided insights into the energetic characteristics of protein-ligand interactions. Thus the identified PqsR antagonists are promising scaffolds for further drug design efforts against this important pathogen.

Rapid and reliable detection and identification of GM events using multiplex PCR coupled with oligonucleotide microarray.

PubMed

Xu, Xiaodan; Li, Yingcong; Zhao, Heng; Wen, Si-yuan; Wang, Sheng-qi; Huang, Jian; Huang, Kun-lun; Luo, Yun-bo

2005-05-18

To devise a rapid and reliable method for the detection and identification of genetically modified (GM) events, we developed a multiplex polymerase chain reaction (PCR) coupled with a DNA microarray system simultaneously aiming at many targets in a single reaction. The system included probes for screening gene, species reference gene, specific gene, construct-specific gene, event-specific gene, and internal and negative control genes. 18S rRNA was combined with species reference genes as internal controls to assess the efficiency of all reactions and to eliminate false negatives. Two sets of the multiplex PCR system were used to amplify four and five targets, respectively. Eight different structure genes could be detected and identified simultaneously for Roundup Ready soybean in a single microarray. The microarray specificity was validated by its ability to discriminate two GM maizes Bt176 and Bt11. The advantages of this method are its high specificity and greatly reduced false-positives and -negatives. The multiplex PCR coupled with microarray technology presented here is a rapid and reliable tool for the simultaneous detection of GM organism ingredients.

Laboratory diagnosis of melioidosis: Past, present and future

PubMed Central

Lau, Susanna KP; Sridhar, Siddharth; Ho, Chi-Chun; Chow, Wang-Ngai; Lee, Kim-Chung; Lam, Ching-Wan; Yuen, Kwok-Yung

2015-01-01

Melioidosis is an emerging, potentially fatal disease caused by Burkholderia pseudomallei, which requires prolonged antibiotic treatment to prevent disease relapse. However, difficulties in laboratory diagnosis of melioidosis may delay treatment and affect disease outcomes. Isolation of B. pseudomallei from clinical specimens has been improved with the use of selective media. However, even with positive cultures, identification of B. pseudomallei can be difficult in clinical microbiology laboratories, especially in non-endemic areas where clinical suspicion is low. Commercial identification systems may fail to distinguish between B. pseudomallei and closely related species such as Burkholderia thailandensis. Genotypic identification of suspected isolates can be achieved by sequencing of gene targets such as groEL which offer higher discriminative power than 16S rRNA. Specific PCR-based identification of B. pseudomallei has also been developed using B. pseudomallei-specific gene targets such as Type III secretion system and Tat-domain protein. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry, a revolutionary technique for pathogen identification, has been shown to be potentially useful for rapid identification of B. pseudomallei, although existing databases require optimization by adding reference spectra for B. pseudomallei. Despite these advances in bacterial identification, diagnostic problems encountered in culture-negative cases remain largely unresolved. Although various serological tests have been developed, they are generally unstandardized “in house” assays and have low sensitivities and specificities. Although specific PCR assays have been applied to direct clinical and environmental specimens, the sensitivities for diagnosis remain to be evaluated. Metabolomics is an uprising tool for studying infectious diseases and may offer a novel approach for exploring potential diagnostic biomarkers. The metabolomics profiles of B. pseudomallei culture supernatants can be potentially distinguished from those of related bacterial species including B. thailandensis. Further studies using bacterial cultures and direct patient samples are required to evaluate the potential of metabolomics for improving diagnosis of melioidosis. PMID:25908634

Multicenter study evaluating the Vitek MS system for identification of medically important yeasts.

PubMed

Westblade, Lars F; Jennemann, Rebecca; Branda, John A; Bythrow, Maureen; Ferraro, Mary Jane; Garner, Omai B; Ginocchio, Christine C; Lewinski, Michael A; Manji, Ryhana; Mochon, A Brian; Procop, Gary W; Richter, Sandra S; Rychert, Jenna A; Sercia, Linda; Burnham, Carey-Ann D

2013-07-01

The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization-time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMérieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20 Candida species (626 isolates, including 58 C. albicans, 62 C. glabrata, and 53 C. krusei isolates), 35 Cryptococcus neoformans isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of C. albicans (n = 58) identified as Candida dubliniensis, one isolate of Candida parapsilosis (n = 73) identified as Candida pelliculosa, and three isolates of Geotrichum klebahnii (n = 6) identified as Geotrichum candidum. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories.

Target Identification Support and Location Support Among Teams of Unmanned Systems Operators

DTIC Science & Technology

2008-12-01

effectiveness and performance, many studies have highlighted the importance of attending to team process (Campion, Medsker, & Higgs, 1993, Campion, Papper ...work groups. Personnel Psychology, 46, 823-850. Campion, M., Papper , E., & Medsker, G., 1996: Relations between work team characteristics and

EOID System Model Validation, Metrics, and Synthetic Clutter Generation

DTIC Science & Technology

2003-09-30

Our long-term goal is to accurately predict the capability of the current generation of laser-based underwater imaging sensors to perform Electro ... Optic Identification (EOID) against relevant targets in a variety of realistic environmental conditions. The models will predict the impact of

A system for household enumeration and re-identification in densely populated slums to facilitate community research, education, and advocacy.

PubMed

Thomson, Dana R; Shitole, Shrutika; Shitole, Tejal; Sawant, Kiran; Subbaraman, Ramnath; Bloom, David E; Patil-Deshmukh, Anita

2014-01-01

We devised and implemented an innovative Location-Based Household Coding System (LBHCS) appropriate to a densely populated informal settlement in Mumbai, India. LBHCS codes were designed to double as unique household identifiers and as walking directions; when an entire community is enumerated, LBHCS codes can be used to identify the number of households located per road (or lane) segment. LBHCS was used in community-wide biometric, mental health, diarrheal disease, and water poverty studies. It also facilitated targeted health interventions by a research team of youth from Mumbai, including intensive door-to-door education of residents, targeted follow-up meetings, and a full census. In addition, LBHCS permitted rapid and low-cost preparation of GIS mapping of all households in the slum, and spatial summation and spatial analysis of survey data. LBHCS was an effective, easy-to-use, affordable approach to household enumeration and re-identification in a densely populated informal settlement where alternative satellite imagery and GPS technologies could not be used.

Rapid identification of moulds and arthroconidial yeasts from positive blood cultures by MALDI-TOF mass spectrometry.

PubMed

de Almeida, João N; Sztajnbok, Jaques; da Silva, Afonso Rafael; Vieira, Vinicius Adriano; Galastri, Anne Layze; Bissoli, Leandro; Litvinov, Nadia; Del Negro, Gilda Maria Barbaro; Motta, Adriana Lopes; Rossi, Flávia; Benard, Gil

2016-11-01

Moulds and arthroconidial yeasts are potential life-threatening agents of fungemia in immunocompromised patients. Fast and accurate identification (ID) of these pathogens hastens initiation of targeted antifungal therapy, thereby improving the patients' prognosis. We describe a new strategy that enabled the identification of moulds and arthroconidial yeasts directly from positive blood cultures by MALDI-TOF mass spectrometry (MS). Positive blood cultures (BCs) with Gram staining showing hyphae and/or arthroconidia were prospectively selected and submitted to an in-house protein extraction protocol. Mass spectra were obtained by Vitek MS™ system, and identifications were carried out with in the research use only (RUO) mode with an extended database (SARAMIS™ [v.4.12] plus in-house database). Fusarium solani, Fusarium verticillioides, Exophiala dermatitidis, Saprochaete clavata, and Trichosporon asahii had correct species ID by MALDI-TOF MS analysis of positive BCs. All cases were related to critically ill patients with high mortality fungemia and direct ID from positive BCs was helpful for rapid administration of targeted antifungal therapy. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Feasibility of CRISPR-Cas9-Based In Vitro Drug Target Identification for Personalized Prostate Cancer Medicine

DTIC Science & Technology

2017-09-01

AWARD NUMBER: W81XWH-16-1-0502 TITLE: Feasibility of CRISPR -Cas9-Based In Vitro Drug Target Identification for Personalized Prostate Cancer Medicine...CONTRACT NUMBER Feasibility of CRISPR -Cas9-Based In Vitro Drug Target Identification for Personalized Prostate Cancer Medicine 5b. GRANT NUMBER...Approved for Public Release; Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT This study tests the feasibility of using CRISPR -Cas9 to

Interventions targeted at primary care practitioners to improve the identification and referral of patients with co-morbid obesity: a realist review protocol.

PubMed

Blane, David N; Macdonald, Sara; Morrison, David; O'Donnell, Catherine A

2015-05-01

Obesity is one of the most significant public health challenges in the developed world. Recent policy has suggested that more can be done in primary care to support adults with obesity. In particular, general practitioners (GPs) and practice nurses (PNs) could improve the identification and referral of adults with obesity to appropriate weight management services. Previous interventions targeted at primary care practitioners in this area have had mixed results, suggesting a more complex interplay between patients, practitioners, and systems. The objectives of this review are (i) to identify the underlying 'programme theory' of interventions targeted at primary care practitioners to improve the identification and referral of adults with obesity and (ii) to explore how and why GPs and PNs identify and refer individuals with obesity, particularly in the context of weight-related co-morbidity. This protocol will explain the rationale for using a realist review approach and outline the key steps in this process. Realist review is a theory-led approach to knowledge synthesis that provides an explanatory analysis aimed at discerning what works, for whom, in what circumstances, how, and why. In this review, scoping interviews with key stakeholders involved in the planning and delivery of adult weight management services in Scotland helped to inform the identification of formal theories - from psychology, sociology, and implementation science - that will be tested as the review progresses. A comprehensive search strategy is described, including scope for iterative searching. Data analysis is outlined in three stages (describing context-mechanism-outcome configurations, exploring patterns in these configurations, and developing and testing middle-range theories, informed by the formal theories previously identified), culminating in the production of explanatory programme theory that considers individual, interpersonal, and institutional/systems-level components. This is the first realist review that we are aware of looking at interventions targeted at primary care practitioners to improve the weight management of adults with obesity. Engagement with stakeholders at an early stage is a unique feature of realist review. This shapes the scope of the review, identification of candidate theories and dissemination strategies. The findings of this review will inform policy and future interventions. PROSPERO CRD42014009391.

Identification of microRNAs with regulatory potential using a matched microRNA-mRNA time-course data.

PubMed

Jayaswal, Vivek; Lutherborrow, Mark; Ma, David D F; Hwa Yang, Yee

2009-05-01

Over the past decade, a class of small RNA molecules called microRNAs (miRNAs) has been shown to regulate gene expression at the post-transcription stage. While early work focused on the identification of miRNAs using a combination of experimental and computational techniques, subsequent studies have focused on identification of miRNA-target mRNA pairs as each miRNA can have hundreds of mRNA targets. The experimental validation of some miRNAs as oncogenic has provided further motivation for research in this area. In this article we propose an odds-ratio (OR) statistic for identification of regulatory miRNAs. It is based on integrative analysis of matched miRNA and mRNA time-course microarray data. The OR-statistic was used for (i) identification of miRNAs with regulatory potential, (ii) identification of miRNA-target mRNA pairs and (iii) identification of time lags between changes in miRNA expression and those of its target mRNAs. We applied the OR-statistic to a cancer data set and identified a small set of miRNAs that were negatively correlated to mRNAs. A literature survey revealed that some of the miRNAs that were predicted to be regulatory, were indeed oncogenic or tumor suppressors. Finally, some of the predicted miRNA targets have been shown to be experimentally valid.

Retrospective Cost Adaptive Control with Concurrent Closed-Loop Identification

NASA Astrophysics Data System (ADS)

Sobolic, Frantisek M.

Retrospective cost adaptive control (RCAC) is a discrete-time direct adaptive control algorithm for stabilization, command following, and disturbance rejection. RCAC is known to work on systems given minimal modeling information which is the leading numerator coefficient and any nonminimum-phase (NMP) zeros of the plant transfer function. This information is normally needed a priori and is key in the development of the filter, also known as the target model, within the retrospective performance variable. A novel approach to alleviate the need for prior modeling of both the leading coefficient of the plant transfer function as well as any NMP zeros is developed. The extension to the RCAC algorithm is the use of concurrent optimization of both the target model and the controller coefficients. Concurrent optimization of the target model and controller coefficients is a quadratic optimization problem in the target model and controller coefficients separately. However, this optimization problem is not convex as a joint function of both variables, and therefore nonconvex optimization methods are needed. Finally, insights within RCAC that include intercalated injection between the controller numerator and the denominator, unveil the workings of RCAC fitting a specific closed-loop transfer function to the target model. We exploit this interpretation by investigating several closed-loop identification architectures in order to extract this information for use in the target model.

Early Probe and Drug Discovery in Academia: A Minireview.

PubMed

Roy, Anuradha

2018-02-09

Drug discovery encompasses processes ranging from target selection and validation to the selection of a development candidate. While comprehensive drug discovery work flows are implemented predominantly in the big pharma domain, early discovery focus in academia serves to identify probe molecules that can serve as tools to study targets or pathways. Despite differences in the ultimate goals of the private and academic sectors, the same basic principles define the best practices in early discovery research. A successful early discovery program is built on strong target definition and validation using a diverse set of biochemical and cell-based assays with functional relevance to the biological system being studied. The chemicals identified as hits undergo extensive scaffold optimization and are characterized for their target specificity and off-target effects in in vitro and in animal models. While the active compounds from screening campaigns pass through highly stringent chemical and Absorption, Distribution, Metabolism, and Excretion (ADME) filters for lead identification, the probe discovery involves limited medicinal chemistry optimization. The goal of probe discovery is identification of a compound with sub-µM activity and reasonable selectivity in the context of the target being studied. The compounds identified from probe discovery can also serve as starting scaffolds for lead optimization studies.

Optimal path planning for video-guided smart munitions via multitarget tracking

NASA Astrophysics Data System (ADS)

Borkowski, Jeffrey M.; Vasquez, Juan R.

2006-05-01

An advent in the development of smart munitions entails autonomously modifying target selection during flight in order to maximize the value of the target being destroyed. A unique guidance law can be constructed that exploits both attribute and kinematic data obtained from an onboard video sensor. An optimal path planning algorithm has been developed with the goals of obstacle avoidance and maximizing the value of the target impacted by the munition. Target identification and classification provides a basis for target value which is used in conjunction with multi-target tracks to determine an optimal waypoint for the munition. A dynamically feasible trajectory is computed to provide constraints on the waypoint selection. Results demonstrate the ability of the autonomous system to avoid moving obstacles and revise target selection in flight.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors.

PubMed

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples.

Evolutionary and Comparative Genomics to Drive Rational Drug Design, with Particular Focus on Neuropeptide Seven-Transmembrane Receptors

PubMed Central

Furlong, Michael; Seong, Jae Young

2017-01-01

Seven transmembrane receptors (7TMRs), also known as G protein-coupled receptors, are popular targets of drug development, particularly 7TMR systems that are activated by peptide ligands. Although many pharmaceutical drugs have been discovered via conventional bulk analysis techniques the increasing availability of structural and evolutionary data are facilitating change to rational, targeted drug design. This article discusses the appeal of neuropeptide-7TMR systems as drug targets and provides an overview of concepts in the evolution of vertebrate genomes and gene families. Subsequently, methods that use evolutionary concepts and comparative analysis techniques to aid in gene discovery, gene function identification, and novel drug design are provided along with case study examples. PMID:28035082

C-mii: a tool for plant miRNA and target identification.

PubMed

Numnark, Somrak; Mhuantong, Wuttichai; Ingsriswang, Supawadee; Wichadakul, Duangdao

2012-01-01

MicroRNAs (miRNAs) have been known to play an important role in several biological processes in both animals and plants. Although several tools for miRNA and target identification are available, the number of tools tailored towards plants is limited, and those that are available have specific functionality, lack graphical user interfaces, and restrict the number of input sequences. Large-scale computational identifications of miRNAs and/or targets of several plants have been also reported. Their methods, however, are only described as flow diagrams, which require programming skills and the understanding of input and output of the connected programs to reproduce. To overcome these limitations and programming complexities, we proposed C-mii as a ready-made software package for both plant miRNA and target identification. C-mii was designed and implemented based on established computational steps and criteria derived from previous literature with the following distinguishing features. First, software is easy to install with all-in-one programs and packaged databases. Second, it comes with graphical user interfaces (GUIs) for ease of use. Users can identify plant miRNAs and targets via step-by-step execution, explore the detailed results from each step, filter the results according to proposed constraints in plant miRNA and target biogenesis, and export sequences and structures of interest. Third, it supplies bird's eye views of the identification results with infographics and grouping information. Fourth, in terms of functionality, it extends the standard computational steps of miRNA target identification with miRNA-target folding and GO annotation. Fifth, it provides helper functions for the update of pre-installed databases and automatic recovery. Finally, it supports multi-project and multi-thread management. C-mii constitutes the first complete software package with graphical user interfaces enabling computational identification of both plant miRNA genes and miRNA targets. With the provided functionalities, it can help accelerate the study of plant miRNAs and targets, especially for small and medium plant molecular labs without bioinformaticians. C-mii is freely available at http://www.biotec.or.th/isl/c-mii for both Windows and Ubuntu Linux platforms.

C-mii: a tool for plant miRNA and target identification

PubMed Central

2012-01-01

Background MicroRNAs (miRNAs) have been known to play an important role in several biological processes in both animals and plants. Although several tools for miRNA and target identification are available, the number of tools tailored towards plants is limited, and those that are available have specific functionality, lack graphical user interfaces, and restrict the number of input sequences. Large-scale computational identifications of miRNAs and/or targets of several plants have been also reported. Their methods, however, are only described as flow diagrams, which require programming skills and the understanding of input and output of the connected programs to reproduce. Results To overcome these limitations and programming complexities, we proposed C-mii as a ready-made software package for both plant miRNA and target identification. C-mii was designed and implemented based on established computational steps and criteria derived from previous literature with the following distinguishing features. First, software is easy to install with all-in-one programs and packaged databases. Second, it comes with graphical user interfaces (GUIs) for ease of use. Users can identify plant miRNAs and targets via step-by-step execution, explore the detailed results from each step, filter the results according to proposed constraints in plant miRNA and target biogenesis, and export sequences and structures of interest. Third, it supplies bird's eye views of the identification results with infographics and grouping information. Fourth, in terms of functionality, it extends the standard computational steps of miRNA target identification with miRNA-target folding and GO annotation. Fifth, it provides helper functions for the update of pre-installed databases and automatic recovery. Finally, it supports multi-project and multi-thread management. Conclusions C-mii constitutes the first complete software package with graphical user interfaces enabling computational identification of both plant miRNA genes and miRNA targets. With the provided functionalities, it can help accelerate the study of plant miRNAs and targets, especially for small and medium plant molecular labs without bioinformaticians. C-mii is freely available at http://www.biotec.or.th/isl/c-mii for both Windows and Ubuntu Linux platforms. PMID:23281648

Features of computerized clinical decision support systems supportive of nursing practice: a literature review.

PubMed

Lee, Seonah

2013-10-01

This study aimed to organize the system features of decision support technologies targeted at nursing practice into assessment, problem identification, care plans, implementation, and outcome evaluation. It also aimed to identify the range of the five stage-related sequential decision supports that computerized clinical decision support systems provided. MEDLINE, CINAHL, and EMBASE were searched. A total of 27 studies were reviewed. The system features collected represented the characteristics of each category from patient assessment to outcome evaluation. Several features were common across the reviewed systems. For the sequential decision support, all of the reviewed systems provided decision support in sequence for patient assessment and care plans. Fewer than half of the systems included problem identification. There were only three systems operating in an implementation stage and four systems in outcome evaluation. Consequently, the key steps for sequential decision support functions were initial patient assessment, problem identification, care plan, and outcome evaluation. Providing decision support in such a full scope will effectively help nurses' clinical decision making. By organizing the system features, a comprehensive picture of nursing practice-oriented computerized decision support systems was obtained; however, the development of a guideline for better systems should go beyond the scope of a literature review.

Millimeter wave sensor requirements for maritime small craft identification

NASA Astrophysics Data System (ADS)

Krapels, Keith; Driggers, Ronald G.; Garcia, Jose; Boettcher, Evelyn; Prather, Dennis; Schuetz, Chrisopher; Samluk, Jesse; Stein, Lee; Kiser, William; Visnansky, Andrew; Grata, Jeremy; Wikner, David; Harris, Russ

2009-09-01

Passive millimeter wave (mmW) imagers have improved in terms of resolution sensitivity and frame rate. Currently, the Office of Naval Research (ONR), along with the US Army Research, Development and Engineering Command, Communications Electronics Research Development and Engineering Center (RDECOM CERDEC) Night Vision and Electronic Sensor Directorate (NVESD), are investigating the current state-of-the-art of mmW imaging systems. The focus of this study was the performance of mmW imaging systems for the task of small watercraft / boat identification field performance. First mmW signatures were collected. This consisted of a set of eight small watercrafts; at 5 different aspects, during the daylight hours over a 48 hour period in the spring of 2008. Target characteristics were measured and characteristic dimension, signatures, and Root Sum Squared of Target's Temperature (RRSΔT) tabulated. Then an eight-alternative, forced choice (8AFC) human perception experiment was developed and conducted at NVESD. The ability of observers to discriminate between small watercraft was quantified. Next, the task difficulty criterion, V50, was quantified by applying this data to NVESD's target acquisition models using the Targeting Task Performance (TTP) metric. These parameters can be used to evaluate sensor field performance for Anti-Terrorism / Force Protection (AT/FP) and navigation tasks for the U.S. Navy, as well as for design and evaluation of imaging passive mmW sensors for both the U.S. Navy and U.S. Coast Guard.

Augmented Reality Tool for the Situational Awareness Improvement of UAV Operators

PubMed Central

Ruano, Susana; Cuevas, Carlos; Gallego, Guillermo; García, Narciso

2017-01-01

Unmanned Aerial Vehicles (UAVs) are being extensively used nowadays. Therefore, pilots of traditional aerial platforms should adapt their skills to operate them from a Ground Control Station (GCS). Common GCSs provide information in separate screens: one presents the video stream while the other displays information about the mission plan and information coming from other sensors. To avoid the burden of fusing information displayed in the two screens, an Augmented Reality (AR) tool is proposed in this paper. The AR system has two functionalities for Medium-Altitude Long-Endurance (MALE) UAVs: route orientation and target identification. Route orientation allows the operator to identify the upcoming waypoints and the path that the UAV is going to follow. Target identification allows a fast target localization, even in the presence of occlusions. The AR tool is implemented following the North Atlantic Treaty Organization (NATO) standards so that it can be used in different GCSs. The experiments show how the AR tool improves significantly the situational awareness of the UAV operators. PMID:28178189

Augmented Reality Tool for the Situational Awareness Improvement of UAV Operators.

PubMed

Ruano, Susana; Cuevas, Carlos; Gallego, Guillermo; García, Narciso

2017-02-06

Unmanned Aerial Vehicles (UAVs) are being extensively used nowadays. Therefore, pilots of traditional aerial platforms should adapt their skills to operate them from a Ground Control Station (GCS). Common GCSs provide information in separate screens: one presents the video stream while the other displays information about the mission plan and information coming from other sensors. To avoid the burden of fusing information displayed in the two screens, an Augmented Reality (AR) tool is proposed in this paper. The AR system has two functionalities for Medium-Altitude Long-Endurance (MALE) UAVs: route orientation and target identification. Route orientation allows the operator to identify the upcoming waypoints and the path that the UAV is going to follow. Target identification allows a fast target localization, even in the presence of occlusions. The AR tool is implemented following the North Atlantic Treaty Organization (NATO) standards so that it can be used in different GCSs. The experiments show how the AR tool improves significantly the situational awareness of the UAV operators.

Observing Active Volcanism on Earth and Beyond With an Autonomous Science Investigation Capability

NASA Astrophysics Data System (ADS)

Davies, A. G.; Mjolsness, E. D.; Fink, W.; Castano, R.; Park, H. G.; Zak, M.; Burl, M. C.

2001-12-01

Operational constraints imposed by restricted downlink and long communication delays make autonomous systems a necessity for exploring dynamic processes in the Solar System and beyond. Our objective is to develop an onboard, modular, automated science analysis tool that will autonomously detect unexpected events, identify rare events at predicted sites, quantify the processes under study, and prioritize the science data and analyses as they are collected. A primary target for this capability is terrestrial active volcanism. Our integrated, science-driven command and control package represents the next stage of the automatic monitoring of volcanic activity pioneered by GOES. The resulting system will maximize science return from day-to-day instrument use and provide immediate reaction to capture the fullest information from infrequent events. For example, a sensor suite consisting of a Galileo-like multi-filter visible wavelength camera and an infrared spectrometer, can acquire high-spatial resolution data of eruptions of lava and volcanic plumes and identify large concentrations of volcanic SO2. After image/spectrum formation, software is applied to the data which is capable of change detection (in the visible and infrared), feature identification (both in imagery and spectra), and novelty detection. In this particular case, the latter module detects change in the parameter space of an advanced multi-component black-body volcanic thermal emission model by means of a novel technique called the "Grey-Box" method which analyzes time series data through a combination of deterministic and stochastic models. This approach can be demonstrated using data obtained by the Galileo spacecraft of ionian volcanism. The system autonomously identifies the most scientifically important targets and prioritizes data and analyses for return. All of these techniques have been successfully demonstrated in laboratory experiments, and are ready to be tested in an operational environment. After identification of a target of interest, an onboard planner prioritizes resources to obtain the best possible dataset of the identified process. We emphasize that the software is modular. The change detection and feature identification modules can be applied to any imaged dataset, and are not confined to volcanic targets. Applications are therefore widespread, across all NASA Enterprises. Examples include detection and quantification of extraterrestrial volcanism (Io, Triton), the monitoring of features in planetary atmospheres (Earth, Gas Giants), the ebb and flow of ices (Earth, Mars), asteriod, comet and supernova detection, change detection in magnetic fields, and identification of structure within radio outbursts.

Neuromorphic Optical Signal Processing and Image Understanding for Automated Target Recognition

DTIC Science & Technology

1989-12-01

34 Stochastic Learning Machine " Neuromorphic Target Identification * Cognitive Networks 3. Conclusions ..... ................ .. 12 4. Publications...16 5. References ...... ................... . 17 6. Appendices ....... .................. 18 I. Optoelectronic Neural Networks and...Learning Machines. II. Stochastic Optical Learning Machine. III. Learning Network for Extrapolation AccesFon For and Radar Target Identification

Biased lineup instructions and face identification from video images.

PubMed

Thompson, W Burt; Johnson, Jaime

2008-01-01

Previous eyewitness memory research has shown that biased lineup instructions reduce identification accuracy, primarily by increasing false-positive identifications in target-absent lineups. Because some attempts at identification do not rely on a witness's memory of the perpetrator but instead involve matching photos to images on surveillance video, the authors investigated the effects of biased instructions on identification accuracy in a matching task. In Experiment 1, biased instructions did not affect the overall accuracy of participants who used video images as an identification aid, but nearly all correct decisions occurred with target-present photo spreads. Both biased and unbiased instructions resulted in high false-positive rates. In Experiment 2, which focused on video-photo matching accuracy with target-absent photo spreads, unbiased instructions led to more correct responses (i.e., fewer false positives). These findings suggest that investigators should not relax precautions against biased instructions when people attempt to match photos to an unfamiliar person recorded on video.

Identification of Buried Objects in GPR Using Amplitude Modulated Signals Extracted from Multiresolution Monogenic Signal Analysis

PubMed Central

Qiao, Lihong; Qin, Yao; Ren, Xiaozhen; Wang, Qifu

2015-01-01

It is necessary to detect the target reflections in ground penetrating radar (GPR) images, so that surface metal targets can be identified successfully. In order to accurately locate buried metal objects, a novel method called the Multiresolution Monogenic Signal Analysis (MMSA) system is applied in ground penetrating radar (GPR) images. This process includes four steps. First the image is decomposed by the MMSA to extract the amplitude component of the B-scan image. The amplitude component enhances the target reflection and suppresses the direct wave and reflective wave to a large extent. Then we use the region of interest extraction method to locate the genuine target reflections from spurious reflections by calculating the normalized variance of the amplitude component. To find the apexes of the targets, a Hough transform is used in the restricted area. Finally, we estimate the horizontal and vertical position of the target. In terms of buried object detection, the proposed system exhibits promising performance, as shown in the experimental results. PMID:26690146

Target scattering characteristics for OAM-based radar

NASA Astrophysics Data System (ADS)

Liu, Kang; Gao, Yue; Li, Xiang; Cheng, Yongqiang

2018-02-01

The target scattering characteristics are crucial for radar systems. However, there is very little study conducted for the recently developed orbital angular momentum (OAM) based radar system. To illustrate the role of OAM-based radar cross section (ORCS), conventional radar equation is modified by taking characteristics of the OAM waves into account. Subsequently, the ORCS is defined in analogy to classical radar cross section (RCS). The unique features of the incident OAM-carrying field are analyzed. The scattered field is derived, and the analytical expressions of ORCSs for metal plate and cylinder targets are obtained. Furthermore, the ORCS and RCS are compared to illustrate the influences of OAM mode number, target size and signal frequency on the ORCS. Analytical studies demonstrate that the mirror-reflection phenomenon disappears and peak values of ORCS are in the non-specular direction. Finally, the ORCS features are summarized to show its advantages in radar target detection. This work can provide theoretical guidance to the design of OAM-based radar as well as the target detection and identification applications.

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

PubMed

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.

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wenzel, Carsten; Riefke, Björn; Gründemann, Stephan

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 oxygenmore » 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-content screen for the identification of compounds that target cells in dormant tumor spheroid regions. • Metabolite profiling by NMR spectroscopy on 3D tumor spheroids. • Identification of respiratory chain inhibitors to specifically induce cell death in inner tumor spheroid regions. • Respiratory chain inhibitors enhance cytostatic based therapy in vitro.« less

Optical stereo video signal processor

NASA Technical Reports Server (NTRS)

Craig, G. D. (Inventor)

1985-01-01

An otpical video signal processor is described which produces a two-dimensional cross-correlation in real time of images received by a stereo camera system. The optical image of each camera is projected on respective liquid crystal light valves. The images on the liquid crystal valves modulate light produced by an extended light source. This modulated light output becomes the two-dimensional cross-correlation when focused onto a video detector and is a function of the range of a target with respect to the stereo camera. Alternate embodiments utilize the two-dimensional cross-correlation to determine target movement and target identification.

Videogrammetric Model Deformation Measurement Technique

NASA Technical Reports Server (NTRS)

Burner, A. W.; Liu, Tian-Shu

2001-01-01

The theory, methods, and applications of the videogrammetric model deformation (VMD) measurement technique used at NASA for wind tunnel testing are presented. The VMD technique, based on non-topographic photogrammetry, can determine static and dynamic aeroelastic deformation and attitude of a wind-tunnel model. Hardware of the system includes a video-rate CCD camera, a computer with an image acquisition frame grabber board, illumination lights, and retroreflective or painted targets on a wind tunnel model. Custom software includes routines for image acquisition, target-tracking/identification, target centroid calculation, camera calibration, and deformation calculations. Applications of the VMD technique at five large NASA wind tunnels are discussed.

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

PubMed Central

Zhang, Yang; Chen, Fuming; Xue, Huijun; Li, Zhao; An, Qiang; Wang, Jianqi; Zhang, Yang

2016-01-01

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. PMID:27801795

Strategies for target identification of antimicrobial natural products.

PubMed

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.

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

PubMed

Zhang, Yang; Chen, Fuming; Xue, Huijun; Li, Zhao; An, Qiang; Wang, Jianqi; Zhang, Yang

2016-10-27

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.

Phage display biopanning and isolation of target-unrelated peptides: in search of nonspecific binders hidden in a combinatorial library.

PubMed

Bakhshinejad, Babak; Zade, Hesam Motaleb; Shekarabi, Hosna Sadat Zahed; Neman, Sara

2016-12-01

Phage display is known as a powerful methodology for the identification of targeting ligands that specifically bind to a variety of targets. The high-throughput screening of phage display combinatorial peptide libraries is performed through the affinity selection method of biopanning. Although phage display selection has proven very successful in the discovery of numerous high-affinity target-binding peptides with potential application in drug discovery and delivery, the enrichment of false-positive target-unrelated peptides (TUPs) without any actual affinity towards the target remains a major problem of library screening. Selection-related TUPs may emerge because of binding to the components of the screening system rather than the target. Propagation-related TUPs may arise as a result of faster growth rate of some phage clones enabling them to outcompete slow-propagating clones. Amplification of the library between rounds of biopanning makes a significant contribution to the selection of phage clones with propagation advantage. Distinguishing nonspecific TUPs from true target binders is of particular importance for the translation of biopanning findings from basic research to clinical applications. Different experimental and in silico approaches are applied to assess the specificity of phage display-derived peptides towards the target. Bioinformatic tools are playing a rapidly growing role in the analysis of biopanning data and identification of target-irrelevant TUPs. Recent progress in the introduction of efficient strategies for TUP detection holds enormous promise for the discovery of clinically relevant cell- and tissue-homing peptides and paves the way for the development of novel targeted diagnostic and therapeutic platforms in pharmaceutical areas.

Systematic Identification of Genes Required for Expression of Androgen Receptor Splice Variants

DTIC Science & Technology

2016-08-01

engineering tool has been developed from bacterial Clustered Regularly Interspaced Short Palindromic Repeats ( CRISPR )/ CRISPR ‐Associated System (Cas...regulation of AR splice variant through CRISPR /Cas screening system. 15. SUBJECT TERMS CRISPR /Cas, Androgen receptor, castration resistance, biomarker 16...control (non-targeting) gRNAs available from Addgene (http://www.addgene.org/ CRISPR /libraries/). Generation of AR3 reporter: We used molecular cloning

Flavivirus RNA Replication: Essential Viral Functions as Targets for Antiviral Therapeutics

DTIC Science & Technology

1991-12-31

We established yellow fever virus ( YFV ) as our study system and assembled all the necessary virologic, molecular biologic, and immunologic reagents for...the detailed study of viral RNA replication. Methodologies for detection, identification, and analysis of YFV polypeptides and RNA species were in...place. Several YFV protesn coding regions were engineered into various surrogate expression systems, and the recombinant proteins thereby produced would

Early phytocannabinoid chemistry to endocannabinoids and beyond.

PubMed

Mechoulam, Raphael; Hanuš, Lumír O; Pertwee, Roger; Howlett, Allyn C

2014-11-01

Isolation and structure elucidation of most of the major cannabinoid constituents--including Δ(9)-tetrahydrocannabinol (Δ(9)-THC), which is the principal psychoactive molecule in Cannabis sativa--was achieved in the 1960s and 1970s. It was followed by the identification of two cannabinoid receptors in the 1980s and the early 1990s and by the identification of the endocannabinoids shortly thereafter. There have since been considerable advances in our understanding of the endocannabinoid system and its function in the brain, which reveal potential therapeutic targets for a wide range of brain disorders.

A multiplex PCR method for the identification of commercially important salmon and trout species (Oncorhynchus and Salmo) in North America.

PubMed

Rasmussen Hellberg, Rosalee S; Morrissey, Michael T; Hanner, Robert H

2010-09-01

The purpose of this study was to develop a species-specific multiplex polymerase chain reaction (PCR) method that allows for the detection of salmon species substitution on the commercial market. Species-specific primers and TaqMan® probes were developed based on a comprehensive collection of mitochondrial 5' cytochrome c oxidase subunit I (COI) deoxyribonucleic acid (DNA) "barcode" sequences. Primers and probes were combined into multiplex assays and tested for specificity against 112 reference samples representing 25 species. Sensitivity and linearity tests were conducted using 10-fold serial dilutions of target DNA (single-species samples) and DNA admixtures containing the target species at levels of 10%, 1.0%, and 0.1% mixed with a secondary species. The specificity tests showed positive signals for the target DNA in both real-time and conventional PCR systems. Nonspecific amplification in both systems was minimal; however, false positives were detected at low levels (1.2% to 8.3%) in conventional PCR. Detection levels were similar for admixtures and single-species samples based on a 30 PCR cycle cut-off, with limits of 0.25 to 2.5 ng (1% to 10%) in conventional PCR and 0.05 to 5.0 ng (0.1% to 10%) in real-time PCR. A small-scale test with food samples showed promising results, with species identification possible even in heavily processed food items. Overall, this study presents a rapid, specific, and sensitive method for salmon species identification that can be applied to mixed-species and heavily processed samples in either conventional or real-time PCR formats. This study provides a newly developed method for salmon and trout species identification that will assist both industry and regulatory agencies in the detection and prevention of species substitution. This multiplex PCR method allows for rapid, high-throughput species identification even in heavily processed and mixed-species samples. An inter-laboratory study is currently being carried out to assess the ability of this method to identify species in a variety of commercial salmon and trout products.

A Conceptual Framework for Creating Culturally Responsive Token Economies

ERIC Educational Resources Information Center

LeBlanc, Gess

2016-01-01

Numerous studies indicate that token economy systems continue to be used by teachers as a means to either increase or decrease behaviours observed in their classrooms. However, studies find that student demographic characteristics such as ethnicity, race, and gender inform teachers' identification of target behaviours. In response to these…

A systems-level approach for metabolic engineering of yeast cell factories.

PubMed

Kim, Il-Kwon; Roldão, António; Siewers, Verena; Nielsen, Jens

2012-03-01

The generation of novel yeast cell factories for production of high-value industrial biotechnological products relies on three metabolic engineering principles: design, construction, and analysis. In the last two decades, strong efforts have been put on developing faster and more efficient strategies and/or technologies for each one of these principles. For design and construction, three major strategies are described in this review: (1) rational metabolic engineering; (2) inverse metabolic engineering; and (3) evolutionary strategies. Independent of the selected strategy, the process of designing yeast strains involves five decision points: (1) choice of product, (2) choice of chassis, (3) identification of target genes, (4) regulating the expression level of target genes, and (5) network balancing of the target genes. At the construction level, several molecular biology tools have been developed through the concept of synthetic biology and applied for the generation of novel, engineered yeast strains. For comprehensive and quantitative analysis of constructed strains, systems biology tools are commonly used and using a multi-omics approach. Key information about the biological system can be revealed, for example, identification of genetic regulatory mechanisms and competitive pathways, thereby assisting the in silico design of metabolic engineering strategies for improving strain performance. Examples on how systems and synthetic biology brought yeast metabolic engineering closer to industrial biotechnology are described in this review, and these examples should demonstrate the potential of a systems-level approach for fast and efficient generation of yeast cell factories. © 2011 Federation of European Microbiological Societies. Published by Blackwell Publishing Ltd. All rights reserved.

Appearance-change instruction effects on eyewitness lineup identification accuracy are not moderated by amount of appearance change.

PubMed

Molinaro, Peter F; Arndorfer, Andrea; Charman, Steve D

2013-12-01

Instructing witnesses that a criminal may have changed appearance prior to showing them a lineup has been shown to increase false identifications without increasing correct identifications (S. D. Charman & G. L. Wells, 2007, Is the appearance-change instruction a good idea? Law and Human Behavior, Vol. 31, pp. 3-22). However, the generalizability of the effects of this appearance-change instruction (ACI) is unknown, and there are reasons to believe that the instruction's effects may be moderated by the amount of appearance change the criminal has actually undergone. The current study tested this hypothesis. Undergraduate students (N = 315) were exposed to a series of target faces and lineups, some of which contained the target and some of which did not, and made identification decisions. Half of the participants received a standard ACI prior to each lineup; the other half did not. The targets varied with respect to the amount to which their appearance had changed. Results indicated that the ACI inflated false identifications without inflating correct identifications, and that these effects did not depend on the amount of appearance change the target had undergone. Current recommendations to administer the ACI seem to be unfounded and may be harmful to the reliability of identification evidence. (c) 2013 APA, all rights reserved

Detection and identification of 700 drugs by multi-target screening with a 3200 Q TRAP LC-MS/MS system and library searching.

PubMed

Dresen, S; Ferreirós, N; Gnann, H; Zimmermann, R; Weinmann, W

2010-04-01

The multi-target screening method described in this work allows the simultaneous detection and identification of 700 drugs and metabolites in biological fluids using a hybrid triple-quadrupole linear ion trap mass spectrometer in a single analytical run. After standardization of the method, the retention times of 700 compounds were determined and transitions for each compound were selected by a "scheduled" survey MRM scan, followed by an information-dependent acquisition using the sensitive enhanced product ion scan of a Q TRAP hybrid instrument. The identification of the compounds in the samples analyzed was accomplished by searching the tandem mass spectrometry (MS/MS) spectra against the library we developed, which contains electrospray ionization-MS/MS spectra of over 1,250 compounds. The multi-target screening method together with the library was included in a software program for routine screening and quantitation to achieve automated acquisition and library searching. With the help of this software application, the time for evaluation and interpretation of the results could be drastically reduced. This new multi-target screening method has been successfully applied for the analysis of postmortem and traffic offense samples as well as proficiency testing, and complements screening with immunoassays, gas chromatography-mass spectrometry, and liquid chromatography-diode-array detection. Other possible applications are analysis in clinical toxicology (for intoxication cases), in psychiatry (antidepressants and other psychoactive drugs), and in forensic toxicology (drugs and driving, workplace drug testing, oral fluid analysis, drug-facilitated sexual assault).

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

PubMed

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.

Target-decoy Based False Discovery Rate Estimation for Large-scale Metabolite Identification.

PubMed

Wang, Xusheng; Jones, Drew R; Shaw, Timothy I; Cho, Ji-Hoon; Wang, Yuanyuan; Tan, Haiyan; Xie, Boer; Zhou, Suiping; Li, Yuxin; Peng, Junmin

2018-05-23

Metabolite identification is a crucial step in mass spectrometry (MS)-based metabolomics. However, it is still challenging to assess the confidence of assigned metabolites. In this study, we report a novel method for estimating false discovery rate (FDR) of metabolite assignment with a target-decoy strategy, in which the decoys are generated through violating the octet rule of chemistry by adding small odd numbers of hydrogen atoms. The target-decoy strategy was integrated into JUMPm, an automated metabolite identification pipeline for large-scale MS analysis, and was also evaluated with two other metabolomics tools, mzMatch and mzMine 2. The reliability of FDR calculation was examined by false datasets, which were simulated by altering MS1 or MS2 spectra. Finally, we used the JUMPm pipeline coupled with the target-decoy strategy to process unlabeled and stable-isotope labeled metabolomic datasets. The results demonstrate that the target-decoy strategy is a simple and effective method for evaluating the confidence of high-throughput metabolite identification.

Is facial skin tone sufficient to produce a cross-racial identification effect?

PubMed

Alley, T R; Schultheis, J A

2001-06-01

Research clearly supports the existence of an other race effect for human faces whereby own-race faces are more accurately perceived and recognized. Why this occurs remains unclear. A computerized program (Mac-a-Mug Pro) for face composition was used to create pairs of target and distractor faces that differed only in skin tone. The six target faces were rated on honesty and aggressiveness by 72 university students, with just one 'Black' and one 'White' face viewed by each student. One week later, they attempted to identify these faces in four lineups: two with target-present and two with target-absent. The order of presentation of targets, lineups, and faces within lineups was varied. Own-race identification was slightly better than cross-racial identification. There was no significant difference in the confidence of responses to own- versus other-race faces. These results indicate that neither morphological variation nor differential confidence is necessary for a cross-racial identification effect.

Multicenter Study Evaluating the Vitek MS System for Identification of Medically Important Yeasts

PubMed Central

Westblade, Lars F.; Jennemann, Rebecca; Branda, John A.; Bythrow, Maureen; Ferraro, Mary Jane; Garner, Omai B.; Ginocchio, Christine C.; Lewinski, Michael A.; Manji, Ryhana; Mochon, A. Brian; Procop, Gary W.; Richter, Sandra S.; Rychert, Jenna A.; Sercia, Linda

2013-01-01

The optimal management of fungal infections is correlated with timely organism identification. Matrix-assisted laser desorption ionization–time of flight (MALDI-TOF) mass spectrometry (MS) is revolutionizing the identification of yeasts isolated from clinical specimens. We present a multicenter study assessing the performance of the Vitek MS system (bioMérieux) in identifying medically important yeasts. A collection of 852 isolates was tested, including 20 Candida species (626 isolates, including 58 C. albicans, 62 C. glabrata, and 53 C. krusei isolates), 35 Cryptococcus neoformans isolates, and 191 other clinically relevant yeast isolates; in total, 31 different species were evaluated. Isolates were directly applied to a target plate, followed by a formic acid overlay. Mass spectra were acquired using the Vitek MS system and were analyzed using the Vitek MS v2.0 database. The gold standard for identification was sequence analysis of the D2 region of the 26S rRNA gene. In total, 823 isolates (96.6%) were identified to the genus level and 819 isolates (96.1%) were identified to the species level. Twenty-four isolates (2.8%) were not identified, and five isolates (0.6%) were misidentified. Misidentified isolates included one isolate of C. albicans (n = 58) identified as Candida dubliniensis, one isolate of Candida parapsilosis (n = 73) identified as Candida pelliculosa, and three isolates of Geotrichum klebahnii (n = 6) identified as Geotrichum candidum. The identification of clinically relevant yeasts using MS is superior to the phenotypic identification systems currently employed in clinical microbiology laboratories. PMID:23658267

Maritime over the Horizon Sensor Integration: High Frequency Surface-Wave-Radar and Automatic Identification System Data Integration Algorithm.

PubMed

Nikolic, Dejan; Stojkovic, Nikola; Lekic, Nikola

2018-04-09

To obtain the complete operational picture of the maritime situation in the Exclusive Economic Zone (EEZ) which lies over the horizon (OTH) requires the integration of data obtained from various sensors. These sensors include: high frequency surface-wave-radar (HFSWR), satellite automatic identification system (SAIS) and land automatic identification system (LAIS). The algorithm proposed in this paper utilizes radar tracks obtained from the network of HFSWRs, which are already processed by a multi-target tracking algorithm and associates SAIS and LAIS data to the corresponding radar tracks, thus forming an integrated data pair. During the integration process, all HFSWR targets in the vicinity of AIS data are evaluated and the one which has the highest matching factor is used for data association. On the other hand, if there is multiple AIS data in the vicinity of a single HFSWR track, the algorithm still makes only one data pair which consists of AIS and HFSWR data with the highest mutual matching factor. During the design and testing, special attention is given to the latency of AIS data, which could be very high in the EEZs of developing countries. The algorithm is designed, implemented and tested in a real working environment. The testing environment is located in the Gulf of Guinea and includes a network of HFSWRs consisting of two HFSWRs, several coastal sites with LAIS receivers and SAIS data provided by provider of SAIS data.

Identification of (antioxidative) plants in herbal pharmaceutical preparations and dietary supplements.

PubMed

Deconinck, Eric; Custers, Deborah; De Beer, Jacques Omer

2015-01-01

The standard procedures for the identification, authentication, and quality control of medicinal plants and herbs are nowadays limited to pure herbal products. No guidelines or procedures, describing the detection or identification of a targeted plant or herb in pharmaceutical preparations or dietary supplements, can be found. In these products the targeted plant is often present together with other components of herbal or synthetic origin. This chapter describes a strategy for the fast development of a chromatographic fingerprint approach that allows the identification of a targeted plant in herbal preparations and dietary supplements. The strategy consists of a standard chromatographic gradient that is tested for the targeted plant with different extraction solvents and different mobile phases. From the results obtained, the optimal fingerprint is selected. Subsequently the samples are analyzed according to the selected methodological parameters, and the obtained fingerprints can be compared with the one obtained for the pure herbal product or a standard preparation. Calculation of the dissimilarity between these fingerprints will result in a probability of presence of the targeted plant. Optionally mass spectrometry can be used to improve specificity, to confirm identification, or to identify molecules with a potential medicinal or antioxidant activity.

Combinatorial Approaches for the Identification of Brain Drug Delivery Targets

PubMed Central

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

2018-01-01

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. PMID:23789958

Microfluidics for Drug Discovery and Development: From Target Selection to Product Lifecycle Management

PubMed Central

Kang, Lifeng; Chung, Bong Geun; Langer, Robert; Khademhosseini, Ali

2009-01-01

Microfluidic technologies’ ability to miniaturize assays and increase experimental throughput have generated significant interest in the drug discovery and development domain. These characteristics make microfluidic systems a potentially valuable tool for many drug discovery and development applications. Here, we review the recent advances of microfluidic devices for drug discovery and development and highlight their applications in different stages of the process, including target selection, lead identification, preclinical tests, clinical trials, chemical synthesis, formulations studies, and product management. PMID:18190858

ARI Image Interpretation Research: 1970-1980

DTIC Science & Technology

1980-07-01

28 3. Index marks on data base stereo pair ... .......... .. 41 4. Identification learning curves for three methods used by interpreters of high...it may be impractical in operational units (but not in the school). Team consensus feedback can increase target identification proficiency and...in target identification can be provided with a minimum of instructor participation using operational imagery as the basic instructional material

The Effects of Signal Erosion and Core Genome Reduction on the Identification of Diagnostic Markers

PubMed Central

Sahl, Jason W.; Vazquez, Adam J.; Hall, Carina M.; Busch, Joseph D.; Tuanyok, Apichai; Mayo, Mark; Schupp, James M.; Lummis, Madeline; Pearson, Talima; Shippy, Kenzie; Allender, Christopher J.; Theobald, Vanessa; Hutcheson, Alex; Korlach, Jonas; LiPuma, John J.; Ladner, Jason; Lovett, Sean; Koroleva, Galina; Palacios, Gustavo; Limmathurotsakul, Direk; Wuthiekanun, Vanaporn; Wongsuwan, Gumphol; Currie, Bart J.

2016-01-01

ABSTRACT Whole-genome sequence (WGS) data are commonly used to design diagnostic targets for the identification of bacterial pathogens. To do this effectively, genomics databases must be comprehensive to identify the strict core genome that is specific to the target pathogen. As additional genomes are analyzed, the core genome size is reduced and there is erosion of the target-specific regions due to commonality with related species, potentially resulting in the identification of false positives and/or false negatives. PMID:27651357

Multisensor data fusion for integrated maritime surveillance

NASA Astrophysics Data System (ADS)

Premji, A.; Ponsford, A. M.

1995-01-01

A prototype Integrated Coastal Surveillance system has been developed on Canada's East Coast to provide effective surveillance out to and beyond the 200 nautical mile Exclusive Economic Zone. The system has been designed to protect Canada's natural resources, and to monitor and control the coastline for smuggling, drug trafficking, and similar illegal activity. This paper describes the Multiple Sensor - Multiple Target data fusion system that has been developed. The fusion processor has been developed around the celebrated Multiple Hypothesis Tracking algorithm which accommodates multiple targets, new targets, false alarms, and missed detections. This processor performs four major functions: plot-to-track association to form individual radar tracks; fusion of radar tracks with secondary sensor reports; track identification and tagging using secondary reports; and track level fusion to form common tracks. Radar data from coherent and non-coherent radars has been used to evaluate the performance of the processor. This paper presents preliminary results.

Quantification of false positive reduction in nucleic acid purification on hemorrhagic fever DNA.

DOE Office of Scientific and Technical Information (OSTI.GOV)

James, Conrad D.; Pohl, Kenneth Roy; Derzon, Mark Steven

2006-11-01

Columbia University has developed a sensitive highly multiplexed system for genetic identification of nucleic acid targets. The primary obstacle to implementing this technology is the high rate of false positives due to high levels of unbound reporters that remain within the system after hybridization. The ability to distinguish between free reporters and reporters bound to targets limits the use of this technology. We previously demonstrated a new electrokinetic method for binary separation of kb pair long DNA molecules and oligonucleotides. The purpose of this project 99864 is to take these previous demonstrations and further develop the technique and hardware formore » field use. Specifically, our objective was to implement separation in a heterogeneous sample (containing target DNA and background oligo), to perform the separation in a flow-based device, and to develop all of the components necessary for field testing a breadboard prototype system.« less

Structure and dynamics of molecular networks: A novel paradigm of drug discovery: A comprehensive review

PubMed Central

Csermely, Peter; Korcsmáros, Tamás; Kiss, Huba J.M.; London, Gábor; Nussinov, Ruth

2013-01-01

Despite considerable progress in genome- and proteome-based high-throughput screening methods and in rational drug design, the increase in approved drugs in the past decade did not match the increase of drug development costs. Network description and analysis not only gives a systems-level understanding of drug action and disease complexity, but can also help to improve the efficiency of drug design. We give a comprehensive assessment of the analytical tools of network topology and dynamics. The state-of-the-art use of chemical similarity, protein structure, protein-protein interaction, signaling, genetic interaction and metabolic networks in the discovery of drug targets is summarized. We propose that network targeting follows two basic strategies. The “central hit strategy” selectively targets central node/edges of the flexible networks of infectious agents or cancer cells to kill them. The “network influence strategy” works against other diseases, where an efficient reconfiguration of rigid networks needs to be achieved. It is shown how network techniques can help in the identification of single-target, edgetic, multi-target and allo-network drug target candidates. We review the recent boom in network methods helping hit identification, lead selection optimizing drug efficacy, as well as minimizing side-effects and drug toxicity. Successful network-based drug development strategies are shown through the examples of infections, cancer, metabolic diseases, neurodegenerative diseases and aging. Summarizing >1200 references we suggest an optimized protocol of network-aided drug development, and provide a list of systems-level hallmarks of drug quality. Finally, we highlight network-related drug development trends helping to achieve these hallmarks by a cohesive, global approach. PMID:23384594

Comparison of Whole-Cell SELEX Methods for the Identification of Staphylococcus Aureus-Specific DNA Aptamers

PubMed Central

Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun

2015-01-01

Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria. PMID:25884791

Comparison of whole-cell SELEX methods for the identification of Staphylococcus aureus-specific DNA aptamers.

PubMed

Moon, Jihea; Kim, Giyoung; Park, Saet Byeol; Lim, Jongguk; Mo, Changyeun

2015-04-15

Whole-cell Systemic Evolution of Ligands by Exponential enrichment (SELEX) is the process by which aptamers specific to target cells are developed. Aptamers selected by whole-cell SELEX have high affinity and specificity for bacterial surface molecules and live bacterial targets. To identify DNA aptamers specific to Staphylococcus aureus, we applied our rapid whole-cell SELEX method to a single-stranded ssDNA library. To improve the specificity and selectivity of the aptamers, we designed, selected, and developed two categories of aptamers that were selected by two kinds of whole-cell SELEX, by mixing and combining FACS analysis and a counter-SELEX process. Using this approach, we have developed a biosensor system that employs a high affinity aptamer for detection of target bacteria. FAM-labeled aptamer sequences with high binding to S. aureus, as determined by fluorescence spectroscopic analysis, were identified, and aptamer A14, selected by the basic whole-cell SELEX using a once-off FACS analysis, and which had a high binding affinity and specificity, was chosen. The binding assay was evaluated using FACS analysis. Our study demonstrated the development of a set of whole-cell SELEX derived aptamers specific to S. aureus; this approach can be used in the identification of other bacteria.

First siRNA library screening in hard-to-transfect HUVEC cells

PubMed Central

Zumbansen, Markus; Altrogge, Ludger M; Spottke, Nicole UE; Spicker, Sonja; Offizier, Sheila M; Domzalski, Sandra BS; St Amand, Allison L; Toell, Andrea; Leake, Devin; Mueller-Hartmann, Herbert A

2010-01-01

Meaningful RNAi-based data for target gene identification are strongly dependent on the use of a biologically relevant cell type and efficient delivery of highly functional siRNA reagents into the selected cell type. Here we report the use of the Amaxa® Nucleofector® 96-well Shuttle® System for siRNA screening in primary cells. Lonza's Clonetics® HUVEC-Human Umbilical Vein Endothelial Cells were transfected with Thermo Scientific Dharmacon siGENOME® siRNA Libraries targeting protein kinases and cell cycle related genes and screened for genes important for cell viability. Of the 37 primary hits, down-regulation of 33 led to reduced proliferation or increased cell death, while down-regulation of two allowed for better cell viability. The validated four genes out of the 16 strongest primary hits (COPB2, PYCS, CDK4 and MYC) influenced cell proliferation to varying degrees, reflecting differing importance for survival of HUVEC cells. Our results demonstrate that the Nucleofector® 96-well Shuttle® System allows the delivery of siRNA libraries in cell types previously considered to be difficult to transfect. Thus, identification and validation of gene targets can now be conducted in primary cells, as the selection of cell types is not limited to those accessible by lipid-mediated transfection. PMID:20628494

Amoxicillin haptenates intracellular proteins that can be transported in exosomes to target cells.

PubMed

Sánchez-Gómez, F J; González-Morena, J M; Vida, Y; Pérez-Inestrosa, E; Blanca, M; Torres, M J; Pérez-Sala, D

2017-03-01

Allergic reactions to β-lactams are among the most frequent causes of drug allergy and constitute an important clinical problem. Drug covalent binding to endogenous proteins (haptenation) is thought to be required for activation of the immune system. Nevertheless, neither the nature nor the role of the drug protein targets involved in this process is fully understood. Here, we aim to identify novel intracellular targets for haptenation by amoxicillin (AX) and their cellular fate. We have treated B lymphocytes with either AX or a biotinylated analog (AX-B). The identification of protein targets for haptenation by AX has been approached by mass spectrometry and immunoaffinity techniques. In addition, intercellular communication mediated by the delivery of vesicles loaded with AX-B-protein adducts has been explored by microscopy techniques. We have observed a complex pattern of AX-haptenated proteins. Several novel targets for haptenation by AX in B lymphocytes have been identified. AX-haptenated proteins were detected in cell lysates and extracellularly, either as soluble proteins or in lymphocyte-derived extracellular vesicles. Interestingly, exosomes from AX-B-treated cells showed a positive biotin signal in electron microscopy. Moreover, they were internalized by endothelial cells, thus supporting their involvement in intercellular transfer of haptenated proteins. These results represent the first identification of AX-mediated haptenation of intracellular proteins. Moreover, they show that exosomes can constitute a novel vehicle for haptenated proteins, and raise the hypothesis that they could provide antigens for activation of the immune system during the allergic response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Human target acquisition performance

NASA Astrophysics Data System (ADS)

Teaney, Brian P.; Du Bosq, Todd W.; Reynolds, Joseph P.; Thompson, Roger; Aghera, Sameer; Moyer, Steven K.; Flug, Eric; Espinola, Richard; Hixson, Jonathan

2012-06-01

The battlefield has shifted from armored vehicles to armed insurgents. Target acquisition (identification, recognition, and detection) range performance involving humans as targets is vital for modern warfare. The acquisition and neutralization of armed insurgents while at the same time minimizing fratricide and civilian casualties is a mounting concern. U.S. Army RDECOM CERDEC NVESD has conducted many experiments involving human targets for infrared and reflective band sensors. The target sets include human activities, hand-held objects, uniforms & armament, and other tactically relevant targets. This paper will define a set of standard task difficulty values for identification and recognition associated with human target acquisition performance.

Targeting dendritic cells--why bother?

PubMed

Kreutz, Martin; Tacken, Paul J; Figdor, Carl G

2013-04-11

Vaccination is among the most efficient forms of immunotherapy. Although sometimes inducing lifelong protective B-cell responses, T-cell-mediated immunity remains challenging. Targeting antigen to dendritic cells (DCs) is an extensively explored concept aimed at improving cellular immunity. The identification of various DC subsets with distinct functional characteristics now allows for the fine-tuning of targeting strategies. Although some of these DC subsets are regarded as superior for (cross-) priming of naive T cells, controversies still remain about which subset represents the best target for immunotherapy. Because targeting the antigen alone may not be sufficient to obtain effective T-cell responses, delivery systems have been developed to target multiple vaccine components to DCs. In this Perspective, we discuss the pros and cons of targeting DCs: if targeting is beneficial at all and which vaccine vehicles and immunization routes represent promising strategies to reach and activate DCs.

shRNA target prediction informed by comprehensive enquiry (SPICE): a supporting system for high-throughput screening of shRNA library.

PubMed

Kamatuka, Kenta; Hattori, Masahiro; Sugiyama, Tomoyasu

2016-12-01

RNA interference (RNAi) screening is extensively used in the field of reverse genetics. RNAi libraries constructed using random oligonucleotides have made this technology affordable. However, the new methodology requires exploration of the RNAi target gene information after screening because the RNAi library includes non-natural sequences that are not found in genes. Here, we developed a web-based tool to support RNAi screening. The system performs short hairpin RNA (shRNA) target prediction that is informed by comprehensive enquiry (SPICE). SPICE automates several tasks that are laborious but indispensable to evaluate the shRNAs obtained by RNAi screening. SPICE has four main functions: (i) sequence identification of shRNA in the input sequence (the sequence might be obtained by sequencing clones in the RNAi library), (ii) searching the target genes in the database, (iii) demonstrating biological information obtained from the database, and (iv) preparation of search result files that can be utilized in a local personal computer (PC). Using this system, we demonstrated that genes targeted by random oligonucleotide-derived shRNAs were not different from those targeted by organism-specific shRNA. The system facilitates RNAi screening, which requires sequence analysis after screening. The SPICE web application is available at http://www.spice.sugysun.org/.

Forecasting the ocean optical environment in support of Navy mine warfare operations

NASA Astrophysics Data System (ADS)

Ladner, S. D.; Arnone, R.; Jolliff, J.; Casey, B.; Matulewski, K.

2012-06-01

A 3D ocean optical forecast system called TODS (Tactical Ocean Data System) has been developed to determine the performance of underwater LIDAR detection/identification systems. TODS fuses optical measurements from gliders, surface satellite optical properties, and 3D ocean forecast circulation models to extend the 2-dimensional surface satellite optics into a 3-dimensional optical volume including subsurface optical layers of beam attenuation coefficient (c) and diver visibility. Optical 3D nowcast and forecasts are combined with electro-optical identification (EOID) models to determine the underwater LIDAR imaging performance field used to identify subsurface mine threats in rapidly changing coastal regions. TODS was validated during a recent mine warfare exercise with Helicopter Mine Countermeasures Squadron (HM-14). Results include the uncertainties in the optical forecast and lidar performance and sensor tow height predictions that are based on visual detection and identification metrics using actual mine target images from the EOID system. TODS is a new capability of coupling the 3D optical environment and EOID system performance and is proving important for the MIW community as both a tactical decision aid and for use in operational planning, improving timeliness and efficiency in clearance operations.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Gasperikova, E.; Smith, J.T.; Morrison, H.F.

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 setmore » 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.« less

Simulation of target interpretation based on infrared image features and psychology principle

NASA Astrophysics Data System (ADS)

Lin, Wei; Chen, Yu-hua; Gao, Hong-sheng; Wang, Zhan-feng; Wang, Ji-jun; Su, Rong-hua; Huang, Yan-ping

2009-07-01

It's an important and complicated process in target interpretation that target features extraction and identification, which effect psychosensorial quantity of interpretation person to target infrared image directly, and decide target viability finally. Using statistical decision theory and psychology principle, designing four psychophysical experiment, the interpretation model of the infrared target is established. The model can get target detection probability by calculating four features similarity degree between target region and background region, which were plotted out on the infrared image. With the verification of a great deal target interpretation in practice, the model can simulate target interpretation and detection process effectively, get the result of target interpretation impersonality, which can provide technique support for target extraction, identification and decision-making.

FilmArray, an Automated Nested Multiplex PCR System for Multi-Pathogen Detection: Development and Application to Respiratory Tract Infection

PubMed Central

Poritz, Mark A.; Blaschke, Anne J.; Byington, Carrie L.; Meyers, Lindsay; Nilsson, Kody; Jones, David E.; Thatcher, Stephanie A.; Robbins, Thomas; Lingenfelter, Beth; Amiott, Elizabeth; Herbener, Amy; Daly, Judy; Dobrowolski, Steven F.; Teng, David H. -F.; Ririe, Kirk M.

2011-01-01

The ideal clinical diagnostic system should deliver rapid, sensitive, specific and reproducible results while minimizing the requirements for specialized laboratory facilities and skilled technicians. We describe an integrated diagnostic platform, the “FilmArray”, which fully automates the detection and identification of multiple organisms from a single sample in about one hour. An unprocessed biologic/clinical sample is subjected to nucleic acid purification, reverse transcription, a high-order nested multiplex polymerase chain reaction and amplicon melt curve analysis. Biochemical reactions are enclosed in a disposable pouch, minimizing the PCR contamination risk. FilmArray has the potential to detect greater than 100 different nucleic acid targets at one time. These features make the system well-suited for molecular detection of infectious agents. Validation of the FilmArray technology was achieved through development of a panel of assays capable of identifying 21 common viral and bacterial respiratory pathogens. Initial testing of the system using both cultured organisms and clinical nasal aspirates obtained from children demonstrated an analytical and clinical sensitivity and specificity comparable to existing diagnostic platforms. We demonstrate that automated identification of pathogens from their corresponding target amplicon(s) can be accomplished by analysis of the DNA melting curve of the amplicon. PMID:22039434

Improved Targeting Through Collaborative Decision-Making and Brain Computer Interfaces

NASA Technical Reports Server (NTRS)

Stoica, Adrian; Barrero, David F.; McDonald-Maier, Klaus

2013-01-01

This paper reports a first step toward a brain-computer interface (BCI) for collaborative targeting. Specifically, we explore, from a broad perspective, how the collaboration of a group of people can increase the performance on a simple target identification task. To this end, we requested a group of people to identify the location and color of a sequence of targets appearing on the screen and measured the time and accuracy of the response. The individual results are compared to a collective identification result determined by simple majority voting, with random choice in case of drawn. The results are promising, as the identification becomes significantly more reliable even with this simple voting and a small number of people (either odd or even number) involved in the decision. In addition, the paper briefly analyzes the role of brain-computer interfaces in collaborative targeting, extending the targeting task by using a BCI instead of a mechanical response.

Linear CCD attitude measurement system based on the identification of the auxiliary array CCD

NASA Astrophysics Data System (ADS)

Hu, Yinghui; Yuan, Feng; Li, Kai; Wang, Yan

2015-10-01

Object to the high precision flying target attitude measurement issues of a large space and large field of view, comparing existing measurement methods, the idea is proposed of using two array CCD to assist in identifying the three linear CCD with multi-cooperative target attitude measurement system, and to address the existing nonlinear system errors and calibration parameters and more problems with nine linear CCD spectroscopic test system of too complicated constraints among camera position caused by excessive. The mathematical model of binocular vision and three linear CCD test system are established, co-spot composition triangle utilize three red LED position light, three points' coordinates are given in advance by Cooperate Measuring Machine, the red LED in the composition of the three sides of a triangle adds three blue LED light points as an auxiliary, so that array CCD is easier to identify three red LED light points, and linear CCD camera is installed of a red filter to filter out the blue LED light points while reducing stray light. Using array CCD to measure the spot, identifying and calculating the spatial coordinates solutions of red LED light points, while utilizing linear CCD to measure three red LED spot for solving linear CCD test system, which can be drawn from 27 solution. Measured with array CCD coordinates auxiliary linear CCD has achieved spot identification, and has solved the difficult problems of multi-objective linear CCD identification. Unique combination of linear CCD imaging features, linear CCD special cylindrical lens system is developed using telecentric optical design, the energy center of the spot position in the depth range of convergence in the direction is perpendicular to the optical axis of the small changes ensuring highprecision image quality, and the entire test system improves spatial object attitude measurement speed and precision.

Automatic Identification of Critical Data Items in a Database to Mitigate the Effects of Malicious Insiders

NASA Astrophysics Data System (ADS)

White, Jonathan; Panda, Brajendra

A major concern for computer system security is the threat from malicious insiders who target and abuse critical data items in the system. In this paper, we propose a solution to enable automatic identification of critical data items in a database by way of data dependency relationships. This identification of critical data items is necessary because insider threats often target mission critical data in order to accomplish malicious tasks. Unfortunately, currently available systems fail to address this problem in a comprehensive manner. It is more difficult for non-experts to identify these critical data items because of their lack of familiarity and due to the fact that data systems are constantly changing. By identifying the critical data items automatically, security engineers will be better prepared to protect what is critical to the mission of the organization and also have the ability to focus their security efforts on these critical data items. We have developed an algorithm that scans the database logs and forms a directed graph showing which items influence a large number of other items and at what frequency this influence occurs. This graph is traversed to reveal the data items which have a large influence throughout the database system by using a novel metric based formula. These items are critical to the system because if they are maliciously altered or stolen, the malicious alterations will spread throughout the system, delaying recovery and causing a much more malignant effect. As these items have significant influence, they are deemed to be critical and worthy of extra security measures. Our proposal is not intended to replace existing intrusion detection systems, but rather is intended to complement current and future technologies. Our proposal has never been performed before, and our experimental results have shown that it is very effective in revealing critical data items automatically.

Development of a rapid and simplified protocol for direct bacterial identification from positive blood cultures by using matrix assisted laser desorption ionization time-of- flight mass spectrometry.

PubMed

Jakovljev, Aleksandra; Bergh, Kåre

2015-11-06

Bloodstream infections represent serious conditions carrying a high mortality and morbidity rate. Rapid identification of microorganisms and prompt institution of adequate antimicrobial therapy is of utmost importance for a successful outcome. Aiming at the development of a rapid, simplified and efficient protocol, we developed and compared two in-house preparatory methods for the direct identification of bacteria from positive blood culture flasks (BD BACTEC FX system) by using matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI TOF MS). Both methods employed saponin and distilled water for erythrocyte lysis. In method A the cellular pellet was overlaid with formic acid on the MALDI TOF target plate for protein extraction, whereas in method B the pellet was exposed to formic acid followed by acetonitrile prior to placing on the target plate. Best results were obtained by method A. Direct identification was achieved for 81.9 % and 65.8 % (50.3 % and 26.2 % with scores >2.0) of organisms by method A and method B, respectively. Overall concordance with final identification was 100 % to genus and 97.9 % to species level. By applying a lower cut-off score value, the levels of identification obtained by method A and method B increased to 89.3 % and 77.8 % of organisms (81.9 % and 65.8 % identified with scores >1.7), respectively. Using the lowered score criteria, concordance with final results was obtained for 99.3 % of genus and 96.6 % of species identifications. The reliability of results, rapid performance (approximately 25 min) and applicability of in-house method A have contributed to implementation of this robust and cost-effective method in our laboratory.

Reading sky and seeing a cloud: On the relevance of events for perceptual simulation.

PubMed

Ostarek, Markus; Vigliocco, Gabriella

2017-04-01

Previous research has shown that processing words with an up/down association (e.g., bird, foot) can influence the subsequent identification of visual targets in congruent location (at the top/bottom of the screen). However, as facilitation and interference were found under similar conditions, the nature of the underlying mechanisms remained unclear. We propose that word comprehension relies on the perceptual simulation of a prototypical event involving the entity denoted by a word in order to provide a general account of the different findings. In 3 experiments, participants had to discriminate between 2 target pictures appearing at the top or the bottom of the screen by pressing the left versus right button. Immediately before the targets appeared, they saw an up/down word belonging to the target's event, an up/down word unrelated to the target, or a spatially neutral control word. Prime words belonging to target event facilitated identification of targets at a stimulus onset asynchrony (SOA) of 250 ms (Experiment 1), but only when presented in the vertical location where they are typically seen, indicating that targets were integrated in the simulations activated by the prime words. Moreover, at the same SOA, there was a robust facilitation effect for targets appearing in their typical location regardless of the prime type. However, when words were presented for 100 ms (Experiment 2) or 800 ms (Experiment 3), only a location nonspecific priming effect was found, suggesting that the visual system was not activated. Implications for theories of semantic processing are discussed. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Does filler database size influence identification accuracy?

PubMed

Bergold, Amanda N; Heaton, Paul

2018-06-01

Police departments increasingly use large photo databases to select lineup fillers using facial recognition software, but this technological shift's implications have been largely unexplored in eyewitness research. Database use, particularly if coupled with facial matching software, could enable lineup constructors to increase filler-suspect similarity and thus enhance eyewitness accuracy (Fitzgerald, Oriet, Price, & Charman, 2013). However, with a large pool of potential fillers, such technologies might theoretically produce lineup fillers too similar to the suspect (Fitzgerald, Oriet, & Price, 2015; Luus & Wells, 1991; Wells, Rydell, & Seelau, 1993). This research proposes a new factor-filler database size-as a lineup feature affecting eyewitness accuracy. In a facial recognition experiment, we select lineup fillers in a legally realistic manner using facial matching software applied to filler databases of 5,000, 25,000, and 125,000 photos, and find that larger databases are associated with a higher objective similarity rating between suspects and fillers and lower overall identification accuracy. In target present lineups, witnesses viewing lineups created from the larger databases were less likely to make correct identifications and more likely to select known innocent fillers. When the target was absent, database size was associated with a lower rate of correct rejections and a higher rate of filler identifications. Higher algorithmic similarity ratings were also associated with decreases in eyewitness identification accuracy. The results suggest that using facial matching software to select fillers from large photograph databases may reduce identification accuracy, and provides support for filler database size as a meaningful system variable. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Identification of promising host-induced silencing targets among genes preferentially transcribed in haustoria of Puccinia

USDA-ARS?s Scientific Manuscript database

Expression of dsRNA fragments of rust pathogen genes in wheat seedlings through the barley stripe mosaic virus (BSMV) based host-induced gene silencing (HIGS) system can reduce the expression of the corresponding genes in the rust fungus. The highest levels of suppression have generally been observe...

Application of the System Identification Technique to Goal-Directed Saccades.

DTIC Science & Technology

1985-07-01

Saccadic eye movements are among the fastest voluntary muscle movements the human body is capable of producing and are characterized by a rapid shift of gaze ...moving the target the same distance the eyeball moves. Collewijn and Van der Mark (9), in their study of the slow phase of optokinetic nystagmus , used

Application of multi-target phytotherapeutic concept in malaria drug discovery: a systems biology approach in biomarker identification.

PubMed

Tarkang, Protus Arrey; Appiah-Opong, Regina; Ofori, Michael F; Ayong, Lawrence S; Nyarko, Alexander K

2016-01-01

There is an urgent need for new anti-malaria drugs with broad therapeutic potential and novel mode of action, for effective treatment and to overcome emerging drug resistance. Plant-derived anti-malarials remain a significant source of bioactive molecules in this regard. The multicomponent formulation forms the basis of phytotherapy. Mechanistic reasons for the poly-pharmacological effects of plants constitute increased bioavailability, interference with cellular transport processes, activation of pro-drugs/deactivation of active compounds to inactive metabolites and action of synergistic partners at different points of the same signaling cascade. These effects are known as the multi-target concept. However, due to the intrinsic complexity of natural products-based drug discovery, there is need to rethink the approaches toward understanding their therapeutic effect. This review discusses the multi-target phytotherapeutic concept and its application in biomarker identification using the modified reverse pharmacology - systems biology approach. Considerations include the generation of a product library, high throughput screening (HTS) techniques for efficacy and interaction assessment, High Performance Liquid Chromatography (HPLC)-based anti-malarial profiling and animal pharmacology. This approach is an integrated interdisciplinary implementation of tailored technology platforms coupled to miniaturized biological assays, to track and characterize the multi-target bioactive components of botanicals as well as identify potential biomarkers. While preserving biodiversity, this will serve as a primary step towards the development of standardized phytomedicines, as well as facilitate lead discovery for chemical prioritization and downstream clinical development.

Design and assessment of engineered CRISPR-Cpf1 and its use for genome editing.

PubMed

Li, Bin; Zeng, Chunxi; Dong, Yizhou

2018-05-01

Cpf1, a CRISPR endonuclease discovered in Prevotella and Francisella 1 bacteria, offers an alternative platform for CRISPR-based genome editing beyond the commonly used CRISPR-Cas9 system originally discovered in Streptococcus pyogenes. This protocol enables the design of engineered CRISPR-Cpf1 components, both CRISPR RNAs (crRNAs) to guide the endonuclease and Cpf1 mRNAs to express the endonuclease protein, and provides experimental procedures for effective genome editing using this system. We also describe quantification of genome-editing activity and off-target effects of the engineered CRISPR-Cpf1 in human cell lines using both T7 endonuclease I (T7E1) assay and targeted deep sequencing. This protocol enables rapid construction and identification of engineered crRNAs and Cpf1 mRNAs to enhance genome-editing efficiency using the CRISPR-Cpf1 system, as well as assessment of target specificity within 2 months. This protocol may also be appropriate for fine-tuning other types of CRISPR systems.

Identification of the Transformational Properties and Transcriptional Targets of the Oncogenic SRY Transcription Factor SOX4

DTIC Science & Technology

2010-01-01

using linker -mediated PCR as described previously (25). Amplified DNA was labeled and hybridized in triplicate by NimbleGen Systems, Inc., to their human...leading edge analysis (37) of these gene sets identified TGFb–induced SMAD3 direct target genes (Supplementary Table S5) as enriched in SOX4 target...3.06E11 PAX5 Paired box 2.07E10 WHN Forkhead 2.94E10 SMAD3 SMAD 1.82E09 SMAD4 SMAD 3.33E09 MYC MYC 6.25E09 NFKAPPAB NF-nB 2.95E08 LEF1/TCF1 LEF

Nucleic acid aptamers: an emerging frontier in cancer therapy.

PubMed

Zhu, Guizhi; Ye, Mao; Donovan, Michael J; Song, Erqun; Zhao, Zilong; Tan, Weihong

2012-11-04

The last two decades have witnessed the development and application of nucleic acid aptamers in a variety of fields, including target analysis, disease therapy, and molecular and cellular engineering. The efficient and widely applicable aptamer selection, reproducible chemical synthesis and modification, generally impressive target binding selectivity and affinity, relatively rapid tissue penetration, low immunogenicity, and rapid systemic clearance make aptamers ideal recognition elements for use as therapeutics or for in vivo delivery of therapeutics. In this feature article, we discuss the development and biomedical application of nucleic acid aptamers, with emphasis on cancer cell aptamer isolation, targeted cancer therapy, oncology biomarker identification and drug discovery.

Ground target recognition using rectangle estimation.

PubMed

Grönwall, Christina; Gustafsson, Fredrik; Millnert, Mille

2006-11-01

We propose a ground target recognition method based on 3-D laser radar data. The method handles general 3-D scattered data. It is based on the fact that man-made objects of complex shape can be decomposed to a set of rectangles. The ground target recognition method consists of four steps; 3-D size and orientation estimation, target segmentation into parts of approximately rectangular shape, identification of segments that represent the target's functional/main parts, and target matching with CAD models. The core in this approach is rectangle estimation. The performance of the rectangle estimation method is evaluated statistically using Monte Carlo simulations. A case study on tank recognition is shown, where 3-D data from four fundamentally different types of laser radar systems are used. Although the approach is tested on rather few examples, we believe that the approach is promising.

Therapeutic targets and new directions for antibodies developed for ovarian cancer

PubMed Central

Bax, Heather J.; Josephs, Debra H.; Pellizzari, Giulia; Spicer, James F.; Montes, Ana; Karagiannis, Sophia N.

2016-01-01

ABSTRACT Antibody therapeutics against different target antigens are widely used in the treatment of different malignancies including ovarian carcinomas, but this disease still requires more effective agents. Improved understanding of the biological features, signaling pathways, and immunological escape mechanisms involved in ovarian cancer has emerged in the past few years. These advances, including an appreciation of the cross-talk between cancer cells and the patient's immune system, have led to the identification of new targets. In turn, potential antibody treatments with various mechanisms of action, including immune activation or toxin-delivery, that are directed at these targets have been developed. Here, we identify established as well as novel targets for antibodies in ovarian cancer, and discuss how they may provide fresh opportunities to identify interventions with enhanced therapeutic potential. PMID:27494775

Combined effects of expectations and visual uncertainty upon detection and identification of a target in the fog.

PubMed

Quétard, Boris; Quinton, Jean-Charles; Colomb, Michèle; Pezzulo, Giovanni; Barca, Laura; Izaute, Marie; Appadoo, Owen Kevin; Mermillod, Martial

2015-09-01

Detecting a pedestrian while driving in the fog is one situation where the prior expectation about the target presence is integrated with the noisy visual input. We focus on how these sources of information influence the oculomotor behavior and are integrated within an underlying decision-making process. The participants had to judge whether high-/low-density fog scenes displayed on a computer screen contained a pedestrian or a deer by executing a mouse movement toward the response button (mouse-tracking). A variable road sign was added on the scene to manipulate expectations about target identity. We then analyzed the timing and amplitude of the deviation of mouse trajectories toward the incorrect response and, using an eye tracker, the detection time (before fixating the target) and the identification time (fixations on the target). Results revealed that expectation of the correct target results in earlier decisions with less deviation toward the alternative response, this effect being partially explained by the facilitation of target identification.

How variations in distance affect eyewitness reports and identification accuracy.

PubMed

Lindsay, R C L; Semmler, Carolyn; Weber, Nathan; Brewer, Neil; Lindsay, Marilyn R

2008-12-01

Witnesses observe crimes at various distances and the courts have to interpret their testimony given the likely quality of witnesses' views of events. We examined how accurately witnesses judged the distance between themselves and a target person, and how distance affected description accuracy, choosing behavior, and identification test accuracy. Over 1,300 participants were approached during normal daily activities, and asked to observe a target person at one of a number of possible distances. Under a Perception, Immediate Memory, or Delayed Memory condition, witnesses provided a brief description of the target, estimated the distance to the target, and then examined a 6-person target-present or target-absent lineup to see if they could identify the target. Errors in distance judgments were often substantial. Description accuracy was mediocre and did not vary systematically with distance. Identification choosing rates were not affected by distance, but decision accuracy declined with distance. Contrary to previous research, a 15-m viewing distance was not critical for discriminating accurate from inaccurate decisions.

Neural network for intelligent query of an FBI forensic database

NASA Astrophysics Data System (ADS)

Uvanni, Lee A.; Rainey, Timothy G.; Balasubramanian, Uma; Brettle, Dean W.; Weingard, Fred; Sibert, Robert W.; Birnbaum, Eric

1997-02-01

Examiner is an automated fired cartridge case identification system utilizing a dual-use neural network pattern recognition technology, called the statistical-multiple object detection and location system (S-MODALS) developed by Booz(DOT)Allen & Hamilton, Inc. in conjunction with Rome Laboratory. S-MODALS was originally designed for automatic target recognition (ATR) of tactical and strategic military targets using multisensor fusion [electro-optical (EO), infrared (IR), and synthetic aperture radar (SAR)] sensors. Since S-MODALS is a learning system readily adaptable to problem domains other than automatic target recognition, the pattern matching problem of microscopic marks for firearms evidence was analyzed using S-MODALS. The physics; phenomenology; discrimination and search strategies; robustness requirements; error level and confidence level propagation that apply to the pattern matching problem of military targets were found to be applicable to the ballistic domain as well. The Examiner system uses S-MODALS to rank a set of queried cartridge case images from the most similar to the least similar image in reference to an investigative fired cartridge case image. The paper presents three independent tests and evaluation studies of the Examiner system utilizing the S-MODALS technology for the Federal Bureau of Investigation.

Are multiple-trial experiments appropriate for eyewitness identification studies? Accuracy, choosing, and confidence across trials.

PubMed

Mansour, J K; Beaudry, J L; Lindsay, R C L

2017-12-01

Eyewitness identification experiments typically involve a single trial: A participant views an event and subsequently makes a lineup decision. As compared to this single-trial paradigm, multiple-trial designs are more efficient, but significantly reduce ecological validity and may affect the strategies that participants use to make lineup decisions. We examined the effects of a number of forensically relevant variables (i.e., memory strength, type of disguise, degree of disguise, and lineup type) on eyewitness accuracy, choosing, and confidence across 12 target-present and 12 target-absent lineup trials (N = 349; 8,376 lineup decisions). The rates of correct rejections and choosing (across both target-present and target-absent lineups) did not vary across the 24 trials, as reflected by main effects or interactions with trial number. Trial number had a significant but trivial quadratic effect on correct identifications (OR = 0.99) and interacted significantly, but again trivially, with disguise type (OR = 1.00). Trial number did not significantly influence participants' confidence in correct identifications, confidence in correct rejections, or confidence in target-absent selections. Thus, multiple-trial designs appear to have minimal effects on eyewitness accuracy, choosing, and confidence. Researchers should thus consider using multiple-trial designs for conducting eyewitness identification experiments.

Molecular targets for small-molecule modulators of circadian clocks

PubMed Central

He, Baokun; Chen, Zheng

2016-01-01

Background Circadian clocks are endogenous timing systems that regulate various aspects of mammalian metabolism, physiology and behavior. Traditional chronotherapy refers to the administration of drugs in a defined circadian time window to achieve optimal pharmacokinetic and therapeutic efficacies. In recent years, substantial efforts have been dedicated to developing novel small-molecule modulators of circadian clocks. Methods Here, we review the recent progress in the identification of molecular targets of small-molecule clock modulators and their efficacies in clock-related disorders. Specifically, we examine the clock components and regulatory factors as possible molecular targets of small molecules, and we review several key clock-related disorders as promising venues for testing the preventive/therapeutic efficacies of these small molecules. Finally, we also discuss circadian regulation of drug metabolism. Results Small molecules can modulate the period, phase and/or amplitude of the circadian cycle. Core clock proteins, nuclear hormone receptors, and clock-related kinases and other epigenetic regulators are promising molecular targets for small molecules. Through these targets small molecules exert protective effects against clock-related disorders including the metabolic syndrome, immune disorders, sleep disorders and cancer. Small molecules can also modulate circadian drug metabolism and response to existing therapeutics. Conclusion Small-molecule clock modulators target clock components or diverse cellular pathways that functionally impinge upon the clock. Target identification of new small-molecule modulators will deepen our understanding of key regulatory nodes in the circadian network. Studies of clock modulators will facilitate their therapeutic applications, alone or in combination, for clock-related diseases. PMID:26750111

A Fisheries Application of a Dual-Frequency Identification Sonar Acoustic Camera

DOE Office of Scientific and Technical Information (OSTI.GOV)

Moursund, Russell A.; Carlson, Thomas J.; Peters, Rock D.

2003-06-01

The uses of an acoustic camera in fish passage research at hydropower facilities are being explored by the U.S. Army Corps of Engineers. The Dual-Frequency Identification Sonar (DIDSON) is a high-resolution imaging sonar that obtains near video-quality images for the identification of objects underwater. Developed originally for the Navy by the University of Washington?s Applied Physics Laboratory, it bridges the gap between existing fisheries assessment sonar and optical systems. Traditional fisheries assessment sonars detect targets at long ranges but cannot record the shape of targets. The images within 12 m of this acoustic camera are so clear that one canmore » see fish undulating as they swim and can tell the head from the tail in otherwise zero-visibility water. In the 1.8 MHz high-frequency mode, this system is composed of 96 beams over a 29-degree field of view. This high resolution and a fast frame rate allow the acoustic camera to produce near video-quality images of objects through time. This technology redefines many of the traditional limitations of sonar for fisheries and aquatic ecology. Images can be taken of fish in confined spaces, close to structural or surface boundaries, and in the presence of entrained air. The targets themselves can be visualized in real time. The DIDSON can be used where conventional underwater cameras would be limited in sampling range to < 1 m by low light levels and high turbidity, and where traditional sonar would be limited by the confined sample volume. Results of recent testing at The Dalles Dam, on the lower Columbia River in Oregon, USA, are shown.« less

Mapping sites of aspirin-induced acetylations in live cells by quantitative acid-cleavable activity-based protein profiling (QA-ABPP)

PubMed Central

Wang, Jigang; Zhang, Chong-Jing; Zhang, Jianbin; He, Yingke; Lee, Yew Mun; Chen, Songbi; Lim, Teck Kwang; Ng, Shukie; Shen, Han-Ming; Lin, Qingsong

2015-01-01

Target-identification and understanding of mechanism-of-action (MOA) are challenging for development of small-molecule probes and their application in biology and drug discovery. For example, although aspirin has been widely used for more than 100 years, its molecular targets have not been fully characterized. To cope with this challenge, we developed a novel technique called quantitative acid-cleavable activity-based protein profiling (QA-ABPP) with combination of the following two parts: (i) activity-based protein profiling (ABPP) and iTRAQ™ quantitative proteomics for identification of target proteins and (ii) acid-cleavable linker-based ABPP for identification of peptides with specific binding sites. It is known that reaction of aspirin with its target proteins leads to acetylation. We thus applied the above technique using aspirin-based probes in human cancer HCT116 cells. We identified 1110 target proteins and 2775 peptides with exact acetylation sites. By correlating these two sets of data, 523 proteins were identified as targets of aspirin. We used various biological assays to validate the effects of aspirin on inhibition of protein synthesis and induction of autophagy which were elicited from the pathway analysis of Aspirin target profile. This technique is widely applicable for target identification in the field of drug discovery and biology, especially for the covalent drugs. PMID:25600173

Open Targets: a platform for therapeutic target identification and validation

PubMed Central

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

Letters in time and retinotopic space.

PubMed

Adelman, James S

2011-10-01

Various phenomena in tachistoscopic word identification and priming (WRODS and LTRS are confused with and prime WORDS and LETTERS) suggest that position-specific channels are not used in the processing of letters in words. Previous approaches to this issue have sought alternative matching rules because they have assumed that these phenomena reveal which stimuli are good but imperfect matches to a particular word-such imperfect matches being taken by the word recognition system as partial evidence for that word. The new Letters in Time and Retinotopic Space model (LTRS) makes the alternative assumption that these phenomena reveal the rates at which different features of the stimulus are extracted, because the stimulus is ambiguous when some features are missing from the percept. LTRS is successfully applied to tachistoscopic identification and form priming data with manipulations of duration and target-foil and prime-target relationships. © 2011 American Psychological Association

[The application of genome editing in identification of plant gene function and crop breeding].

PubMed

Zhou, Xiang-chun; Xing, Yong-zhong

2016-03-01

Plant genome can be modified via current biotechnology with high specificity and excellent efficiency. Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (Cas9) system are the key engineered nucleases used in the genome editing. Genome editing techniques enable gene targeted mutagenesis, gene knock-out, gene insertion or replacement at the target sites during the endogenous DNA repair process, including non-homologous end joining (NHEJ) and homologous recombination (HR), triggered by the induction of DNA double-strand break (DSB). Genome editing has been successfully applied in the genome modification of diverse plant species, such as Arabidopsis thaliana, Oryza sativa, and Nicotiana tabacum. In this review, we summarize the application of genome editing in identification of plant gene function and crop breeding. Moreover, we also discuss the improving points of genome editing in crop precision genetic improvement for further study.

Calculation and simulation of atmospheric refraction effects in maritime environments

NASA Astrophysics Data System (ADS)

Dion, Denis, Jr.; Gardenal, Lionel; Lahaie, P.; Forand, J. Luc

2001-01-01

Near the sea surface, atmospheric refraction and turbulence affect both IR transmission and image quality. This produces an impact on both the detection and classification/identification of targets. With the financial participation of the U.S. Office of Naval Research (ONR), Canada's Defence Research Establishment Valcartier (DREV) is developing PRIME (Propagation Resources In the Maritime Environment), a computer model aimed at describing the overall atmospheric effects on IR imagery systems in the marine surface layer. PRIME can be used as a complement to MODTRAN to compute the effective transmittance in the marine surface layer, taking into account the lens effects caused by refraction. It also provides information on image degradation caused by both refraction and turbulence. This paper reviews the refraction phenomena that take place in the surface layer and discusses their effects on target detection and identification. We then show how PRIME can benefit detection studies and image degradation simulations.

Photonics: From target recognition to lesion detection

NASA Technical Reports Server (NTRS)

Henry, E. Michael

1994-01-01

Since 1989, Martin Marietta has invested in the development of an innovative concept for robust real-time pattern recognition for any two-dimensioanal sensor. This concept has been tested in simulation, and in laboratory and field hardware, for a number of DOD and commercial uses from automatic target recognition to manufacturing inspection. We have now joined Rose Health Care Systems in developing its use for medical diagnostics. The concept is based on determining regions of interest by using optical Fourier bandpassing as a scene segmentation technique, enhancing those regions using wavelet filters, passing the enhanced regions to a neural network for analysis and initial pattern identification, and following this initial identification with confirmation by optical correlation. The optical scene segmentation and pattern confirmation are performed by the same optical module. The neural network is a recursive error minimization network with a small number of connections and nodes that rapidly converges to a global minimum.

Identification accuracy of children versus adults: a meta-analysis.

PubMed

Pozzulo, J D; Lindsay, R C

1998-10-01

Identification accuracy of children and adults was examined in a meta-analysis. Preschoolers (M = 4 years) were less likely than adults to make correct identifications. Children over the age of 5 did not differ significantly from adults with regard to correct identification rate. Children of all ages examined were less likely than adults to correctly reject a target-absent lineup. Even adolescents (M = 12-13 years) did not reach an adult rate of correct rejection. Compared to simultaneous lineup presentation, sequential lineups increased the child-adult gap for correct rejections. Providing child witnesses with identification practice or training did not increase their correct rejection rates. Suggestions for children's inability to correctly reject target-absent lineups are discussed. Future directions for identification research are presented.

Membrane protease degradomics: proteomic identification and quantification of cell surface protease substrates.

PubMed

Butler, Georgina S; Dean, Richard A; Smith, Derek; Overall, Christopher M

2009-01-01

The modification of cell surface proteins by plasma membrane and soluble proteases is important for physiological and pathological processes. Methods to identify shed and soluble substrates are crucial to further define the substrate repertoire, termed the substrate degradome, of individual proteases. Identifying protease substrates is essential to elucidate protease function and involvement in different homeostatic and disease pathways. This characterisation is also crucial for drug target identification and validation, which would then allow the rational design of specific targeted inhibitors for therapeutic intervention. We describe two methods for identifying and quantifying shed cell surface protease targets in cultured cells utilising Isotope-Coded Affinity Tags (ICAT) and Isobaric Tags for Relative and Absolute Quantification (iTRAQ). As a model system to develop these techniques, we chose a cell-membrane expressed matrix metalloproteinase, MMP-14, but the concepts can be applied to proteases of other classes. By over-expression, or conversely inhibition, of a particular protease with careful selection of control conditions (e.g. vector or inactive protease) and differential labelling, shed proteins can be identified and quantified by mass spectrometry (MS), MS/MS fragmentation and database searching.

Complementary Approaches to Existing Target Based Drug Discovery for Identifying Novel Drug Targets.

PubMed

Vasaikar, Suhas; Bhatia, Pooja; Bhatia, Partap G; Chu Yaiw, Koon

2016-11-21

In the past decade, it was observed that the relationship between the emerging New Molecular Entities and the quantum of R&D investment has not been favorable. There might be numerous reasons but few studies stress the introduction of target based drug discovery approach as one of the factors. Although a number of drugs have been developed with an emphasis on a single protein target, yet identification of valid target is complex. The approach focuses on an in vitro single target, which overlooks the complexity of cell and makes process of validation drug targets uncertain. Thus, it is imperative to search for alternatives rather than looking at success stories of target-based drug discovery. It would be beneficial if the drugs were developed to target multiple components. New approaches like reverse engineering and translational research need to take into account both system and target-based approach. This review evaluates the strengths and limitations of known drug discovery approaches and proposes alternative approaches for increasing efficiency against treatment.

A re-examination of the effects of biased lineup instructions in eyewitness identification.

PubMed

Clark, Steven E

2005-10-01

A meta-analytic review of research comparing biased and unbiased instructions in eyewitness identification experiments showed an asymmetry; specifically, that biased instructions led to a large and consistent decrease in accuracy in target-absent lineups, but produced inconsistent results for target-present lineups, with an average effect size near zero (Steblay, 1997). The results for target-present lineups are surprising, and are inconsistent with statistical decision theories (i.e., Green & Swets, 1966). A re-examination of the relevant studies and the meta-analysis of those studies shows clear evidence that correct identification rates do increase with biased lineup instructions, and that biased witnesses make correct identifications at a rate considerably above chance. Implications for theory, as well as police procedure and policy, are discussed.

A re-examination of the effects of biased lineup instructions in eyewitness identification.

PubMed

Clark, Steven E

2005-08-01

A meta-analytic review of research comparing biased and unbiased instructions in eyewitness identification experiments showed an asymmetry, specifically that biased instructions led to a large and consistent decrease in accuracy in target-absent lineups, but produced inconsistent results for target-present lineups, with an average effect size near zero (N. M. Steblay, 1997). The results for target-present lineups are surprising, and are inconsistent with statistical decision theories (i.e., D. M. Green & J. A. Swets, 1966). A re-examination of the relevant studies and the meta-analysis of those studies shows clear evidence that correct identification rates do increase with biased lineup instructions, and that biased witnesses make correct identifications at a rate considerably above chance. Implications for theory, as well as police procedure and policy, are discussed.

Visually-guided attention enhances target identification in a complex auditory scene.

PubMed

Best, Virginia; Ozmeral, Erol J; Shinn-Cunningham, Barbara G

2007-06-01

In auditory scenes containing many similar sound sources, sorting of acoustic information into streams becomes difficult, which can lead to disruptions in the identification of behaviorally relevant targets. This study investigated the benefit of providing simple visual cues for when and/or where a target would occur in a complex acoustic mixture. Importantly, the visual cues provided no information about the target content. In separate experiments, human subjects either identified learned birdsongs in the presence of a chorus of unlearned songs or recalled strings of spoken digits in the presence of speech maskers. A visual cue indicating which loudspeaker (from an array of five) would contain the target improved accuracy for both kinds of stimuli. A cue indicating which time segment (out of a possible five) would contain the target also improved accuracy, but much more for birdsong than for speech. These results suggest that in real world situations, information about where a target of interest is located can enhance its identification, while information about when to listen can also be helpful when targets are unfamiliar or extremely similar to their competitors.

Visually-guided Attention Enhances Target Identification in a Complex Auditory Scene

PubMed Central

Ozmeral, Erol J.; Shinn-Cunningham, Barbara G.

2007-01-01

In auditory scenes containing many similar sound sources, sorting of acoustic information into streams becomes difficult, which can lead to disruptions in the identification of behaviorally relevant targets. This study investigated the benefit of providing simple visual cues for when and/or where a target would occur in a complex acoustic mixture. Importantly, the visual cues provided no information about the target content. In separate experiments, human subjects either identified learned birdsongs in the presence of a chorus of unlearned songs or recalled strings of spoken digits in the presence of speech maskers. A visual cue indicating which loudspeaker (from an array of five) would contain the target improved accuracy for both kinds of stimuli. A cue indicating which time segment (out of a possible five) would contain the target also improved accuracy, but much more for birdsong than for speech. These results suggest that in real world situations, information about where a target of interest is located can enhance its identification, while information about when to listen can also be helpful when targets are unfamiliar or extremely similar to their competitors. PMID:17453308

Examination of soldier target recognition with direct view optics

NASA Astrophysics Data System (ADS)

Long, Frederick H.; Larkin, Gabriella; Bisordi, Danielle; Dorsey, Shauna; Marianucci, Damien; Goss, Lashawnta; Bastawros, Michael; Misiuda, Paul; Rodgers, Glenn; Mazz, John P.

2017-10-01

Target recognition and identification is a problem of great military and scientific importance. To examine the correlation between target recognition and optical magnification, ten U.S. Army soldiers were tasked with identifying letters on targets at 800 and 1300 meters away. Letters were used since they are a standard method for measuring visual acuity. The letters were approximately 90 cm high, which is the size of a well-known rifle. Four direct view optics with angular magnifications of 1.5x, 4x, 6x, and 9x were used. The goal of this approach was to measure actual probabilities for correct target identification. Previous scientific literature suggests that target recognition can be modeled as a linear response problem in angular frequency space using the established values for the contrast sensitivity function for a healthy human eye and the experimentally measured modulation transfer function of the optic. At the 9x magnification, the soldiers could identify the letters with almost no errors (i.e., 97% probability of correct identification). At lower magnification, errors in letter identification were more frequent. The identification errors were not random but occurred most frequently with a few pairs of letters (e.g., O and Q), which is consistent with the literature for letter recognition. In addition, in the small subject sample of ten soldiers, there was considerable variation in the observer recognition capability at 1.5x and a range of 800 meters. This can be directly attributed to the variation in the observer visual acuity.

Integrated IR sensors

NASA Astrophysics Data System (ADS)

Tom, Michael; Trujillo, Edward

1994-06-01

Integrated infrared (IR) sensors which exploit modular avionics concepts can provide features such as operational flexibility, enhanced stealthiness, and ease of maintenance to meet the demands of tactical, airborne sensor systems. On-board, tactical airborne sensor systems perform target acquisition, tracking, identification, threat warning, missile launch detection, and ground mapping in support of situation awareness, self-defense, navigation, target attack, weapon support, and reconnaissance activities. The use of sensor suites for future tactical aircraft such as US Air Force's multirole fighter require a blend of sensor inputs and outputs that may vary over time. It is expected that special-role units of these tactical aircraft will be formed to conduct tasks and missions such as anti-shipping, reconnaissance, or suppression of enemy air defenses.

oPOSSUM: identification of over-represented transcription factor binding sites in co-expressed genes

PubMed Central

Ho Sui, Shannan J.; Mortimer, James R.; Arenillas, David J.; Brumm, Jochen; Walsh, Christopher J.; Kennedy, Brian P.; Wasserman, Wyeth W.

2005-01-01

Targeted transcript profiling studies can identify sets of co-expressed genes; however, identification of the underlying functional mechanism(s) is a significant challenge. Established methods for the analysis of gene annotations, particularly those based on the Gene Ontology, can identify functional linkages between genes. Similar methods for the identification of over-represented transcription factor binding sites (TFBSs) have been successful in yeast, but extension to human genomics has largely proved ineffective. Creation of a system for the efficient identification of common regulatory mechanisms in a subset of co-expressed human genes promises to break a roadblock in functional genomics research. We have developed an integrated system that searches for evidence of co-regulation by one or more transcription factors (TFs). oPOSSUM combines a pre-computed database of conserved TFBSs in human and mouse promoters with statistical methods for identification of sites over-represented in a set of co-expressed genes. The algorithm successfully identified mediating TFs in control sets of tissue-specific genes and in sets of co-expressed genes from three transcript profiling studies. Simulation studies indicate that oPOSSUM produces few false positives using empirically defined thresholds and can tolerate up to 50% noise in a set of co-expressed genes. PMID:15933209

Lineup Administrator Influences on Eyewitness Identification Decisions

ERIC Educational Resources Information Center

Clark, Steven E.; Marshall, Tanya E.; Rosenthal, Robert

2009-01-01

The present research examines how a lineup administrator may influence eyewitness identification decisions through different forms of influence, after providing the witness with standard, unbiased instructions. Participant-witnesses viewed a staged crime and were later shown a target-present or target-absent lineup. The lineup administrators…

Underwater electro-optical system for mine identification

NASA Astrophysics Data System (ADS)

Strand, Michael P.

1995-06-01

The Electro-Optic Identification (EOID) Sensors project is developing a Laser Visual Iidentification Sensor (LVIS) for identification of proud, partially buried, and moored mines in shallow water/very shallow water. LVIS will be deployed in small diameter underwater vehicles, including unmanned underwater vehicles (UUVs). Since the mission is mine identification, LVIS must: a) deliver high quality images in turbid coastal waters, while b) being compatible with the size and power constraints imposed by the intended deployment platforms. This project is sponsored by the Office of Naval Research, as a part of the AOA Mine Reconnaissance/Hunter program. High quality images which retain target detail and contrast are required for mine identification. LVIS will be designed to produce images of minelike contacts (MLC) of sufficient quality to allow identification while operating in turbid coastal waters from a small diameter UUV. Technology goals for the first generation LVIS are a) identification range up to 40 feet for proud, partially buried, and moored MLCs under coastal water conditions; b) day/night operation from a UUV operating at speeds up to 4 knots; c) power consumption less than 500 watts, with 275 watts being typical; and d) packaged within a 32-inch long portion of a 21-inch diameter vehicle section.

Fast and confident: postdicting eyewitness identification accuracy in a field study.

PubMed

Sauerland, Melanie; Sporer, Siegfried L

2009-03-01

The combined postdictive value of postdecision confidence, decision time, and Remember-Know-Familiar (RKF) judgments as markers of identification accuracy was evaluated with 10 targets and 720 participants. In a pedestrian area, passers-by were asked for directions. Identifications were made from target-absent or target-present lineups. Fast (optimum time boundary at 6 seconds) and confident (optimum confidence boundary at 90%) witnesses were highly accurate, slow and nonconfident witnesses highly inaccurate. Although this combination of postdictors was clearly superior to using either postdictor by itself these combinations refer only to a subsample of choosers. Know answers were associated with higher identification performance than Familiar answers, with no difference between Remember and Know answers. The results of participants' post hoc decision time estimates paralleled those with measured decision times. To explore decision strategies of nonchoosers, three subgroups were formed according to their reasons given for rejecting the lineup. Nonchoosers indicating that the target had simply been absent made faster and more confident decisions than nonchoosers stating lack of confidence or lack of memory. There were no significant differences with regard to identification performance across nonchooser groups. (PsycINFO Database Record (c) 2009 APA, all rights reserved).

The neural substrates of action identification.

PubMed

Marsh, Abigail A; Kozak, Megan N; Wegner, Daniel M; Reid, Marguerite E; Yu, Henry H; Blair, R J R

2010-12-01

Mentalization is the process by which an observer views a target as possessing higher cognitive faculties such as goals, intentions and desires. Mentalization can be assessed using action identification paradigms, in which observers choose mentalistic (goals-focused) or mechanistic (action-focused) descriptions of targets' actions. Neural structures that play key roles in inferring goals and intentions from others' observed or imagined actions include temporo-parietal junction, ventral premotor cortex and extrastriate body area. We hypothesized that these regions play a role in action identification as well. Data collected using functional magnetic resonance imaging (fMRI) confirmed our predictions that activity in ventral premotor cortex and middle temporal gyrus near the extrastriate body area varies both as a function of the valence of the target and the extent to which actions are identified as goal-directed. In addition, the inferior parietal lobule is preferentially engaged when participants identify the actions of mentalized targets. Functional connectivity analyses suggest support from other regions, including the medial prefrontal cortex and amygdala, during mentalization. We found correlations between action identification and Autism Quotient scores, suggesting that understanding the neural correlates of action identification may enhance our understanding of the underpinnings of essential social cognitive processes.

Secure Embedded Systems

DTIC Science & Technology

2016-02-26

UAS) to illustrate how we use cryptography to ensure confidentiality and integrity. Using this example, we demonstrate the identification of...potential attack targets by considering the CONOPS, the development of countermeasures to these attacks, and the design and implementation of a cryptography ...based security architecture. Because cryptography does not directly enable availability, we also provide insight into the ongoing research that

Effects of weighting schemes on the identification of wildlife corridors generated with least-cost methods

Treesearch

Sean A. Parks; Kevin S. McKelvey; Michael K. Schwartz

2012-01-01

The importance of movement corridors for maintaining connectivity within metapopulations of wild animals is a cornerstone of conservation. One common approach for determining corridor locations is least-cost corridor (LCC) modeling, which uses algorithms within a geographic information system to search for routes with the lowest cumulative resistance between target...

Tree species differentiation using intensity data derived from leaf-on and leaf-off airborne laser scanner data

Treesearch

Sooyoung Kim; Robert J. McGaughey; Hans-Erik Andersen; Gerard Schreuder

2009-01-01

Tree species identification is important for a variety of natural resource management and monitoring activities including riparian buffer characterization, wildfire risk assessment, biodiversity monitoring, and wildlife habitat assessment. Intensity data recorded for each laser point in a LIDAR system is related to the spectral reflectance of the target material and...

Regularities in eyewitness identification.

PubMed

Clark, Steven E; Howell, Ryan T; Davey, Sherrie L

2008-06-01

What do eyewitness identification experiments typically show? We address this question through a meta-analysis of 94 comparisons between target-present and target-absent lineups. The analyses showed that: (a) correct identifications and correct-nonidentifications were uncorrelated, (b) suspect identifications were more diagnostic with respect to the suspect's guilt or innocence than any other response, (c) nonidentifications were diagnostic of the suspect's innocence, (d) the diagnosticity of foil identifications depended on lineup composition, and (e) don't know responses were nondiagnostic with respect to guilt or innocence. Results of diagnosticity analyses for simultaneous and sequential lineups varied for full-sample versus direct-comparison analyses. Diagnosticity patterns also varied as a function of lineup composition. Theoretical, forensic, and legal implications are discussed.

Identification of Direct Protein Targets of Small Molecules

PubMed Central

2010-01-01

Small-molecule target identification is a vital and daunting task for the chemical biology community as well as for researchers interested in applying the power of chemical genetics to impact biology and medicine. To overcome this “target ID” bottleneck, new technologies are being developed that analyze protein–drug interactions, such as drug affinity responsive target stability (DARTS), which aims to discover the direct binding targets (and off targets) of small molecules on a proteome scale without requiring chemical modification of the compound. Here, we review the DARTS method, discuss why it works, and provide new perspectives for future development in this area. PMID:21077692

Deployment of spatial attention to words in central and peripheral vision.

PubMed

Ducrot, Stéphanie; Grainger, Jonathan

2007-05-01

Four perceptual identification experiments examined the influence of spatial cues on the recognition of words presented in central vision (with fixation on either the first or last letter of the target word) and in peripheral vision (displaced left or right of a central fixation point). Stimulus location had a strong effect on word identification accuracy in both central and peripheral vision, showing a strong right visual field superiority that did not depend on eccentricity. Valid spatial cues improved word identification for peripherally presented targets but were largely ineffective for centrally presented targets. Effects of spatial cuing interacted with visual field effects in Experiment 1, with valid cues reducing the right visual field superiority for peripherally located targets, but this interaction was shown to depend on the type of neutral cue. These results provide further support for the role of attentional factors in visual field asymmetries obtained with targets in peripheral vision but not with centrally presented targets.

Structure identification by Mass Spectrometry Non-Targeted Analysis using the US EPA’s CompTox Chemistry Dashboard

EPA Science Inventory

Identification of unknowns in mass spectrometry based non-targeted analyses (NTA) requires the integration of complementary pieces of data to arrive at a confident, consensus structure. Researchers use chemical reference databases, spectral matching, fragment prediction tools, r...

Active imaging system performance model for target acquisition

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Teaney, Brian; Nguyen, Quang; Jacobs, Eddie L.; Halford, Carl E.; Tofsted, David H.

2007-04-01

The U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate has developed a laser-range-gated imaging system performance model for the detection, recognition, and identification of vehicle targets. The model is based on the established US Army RDECOM CERDEC NVESD sensor performance models of the human system response through an imaging system. The Java-based model, called NVLRG, accounts for the effect of active illumination, atmospheric attenuation, and turbulence effects relevant to LRG imagers, such as speckle and scintillation, and for the critical sensor and display components. This model can be used to assess the performance of recently proposed active SWIR systems through various trade studies. This paper will describe the NVLRG model in detail, discuss the validation of recent model components, present initial trade study results, and outline plans to validate and calibrate the end-to-end model with field data through human perception testing.

Multiple Level Crowding: Crowding at the Object Parts Level and at the Object Configural level.

PubMed

Kimchi, Ruth; Pirkner, Yossef

2015-01-01

In crowding, identification of a peripheral target in the presence of nearby flankers is worse than when the target appears alone. Prevailing theories hold that crowding occurs because of integration or "pooling" of low-level features at a single, relatively early stage of visual processing. Recent studies suggest that crowding can occur also between high-level object representations. The most relevant findings come from studies with faces and may be specific to faces. We examined whether crowding can occur at the object configural level in addition to part-level crowding, using nonface objects. Target (a disconnected square or diamond made of four elements) identification was measured at varying eccentricities. The flankers were similar either to the target parts or to the target configuration. The results showed crowding in both cases: Flankers interfered with target identification such that identification accuracy decreased with an increase in eccentricity, and no interference was observed at the fovea. Crowding by object parts, however, was weaker and had smaller spatial extent than crowding by object configurations; we related this finding to the relationship between crowding and perceptual organization. These results provide strong evidence that crowding occurs not only between object parts but also between configural representations of objects. © The Author(s) 2015.

A systematic approach to prioritize drug targets using machine learning, a molecular descriptor-based classification model, and high-throughput screening of plant derived molecules: a case study in oral cancer.

PubMed

Randhawa, Vinay; Kumar Singh, Anil; Acharya, Vishal

2015-12-01

Systems-biology inspired identification of drug targets and machine learning-based screening of small molecules which modulate their activity have the potential to revolutionize modern drug discovery by complementing conventional methods. To utilize the effectiveness of such pipelines, we first analyzed the dysregulated gene pairs between control and tumor samples and then implemented an ensemble-based feature selection approach to prioritize targets in oral squamous cell carcinoma (OSCC) for therapeutic exploration. Based on the structural information of known inhibitors of CXCR4-one of the best targets identified in this study-a feature selection was implemented for the identification of optimal structural features (molecular descriptor) based on which a classification model was generated. Furthermore, the CXCR4-centered descriptor-based classification model was finally utilized to screen a repository of plant derived small-molecules to obtain potential inhibitors. The application of our methodology may assist effective selection of the best targets which may have previously been overlooked, that in turn will lead to the development of new oral cancer medications. The small molecules identified in this study can be ideal candidates for trials as potential novel anti-oral cancer agents. Importantly, distinct steps of this whole study may provide reference for the analysis of other complex human diseases.

A new miniature hand-held solar-blind reagentless standoff chemical, biological, and explosives (CBE) sensor

NASA Astrophysics Data System (ADS)

Hug, W. F.; Reid, R. D.; Bhartia, R.; Lane, A. L.

2008-04-01

Improvised explosive devices (IEDs), vehicle-borne improvised explosive devices (VBIEDs), and suicide bombers are a major threat to many countries and their citizenry. The ability to detect trace levels of these threats with a miniature, hand-held, reagentless, standoff sensor represents a major improvement in the state of the art of CBE surface sensors. Photon Systems, Inc., in collaboration with Jet Propulsion Laboratory, recently demonstrated a new technology hand-held sensor for reagentless, close-range, standoff detection and identification of trace levels CBE materials on surfaces. This targeted ultraviolet CBE (TUCBE) sensor is the result of an Army Phase I STTR program. The resulting 5lb, 5W, flashlight-sized sensor can discriminate CBE from background materials using a combination of deep UV excited resonance Raman (RR) and laser induced native fluorescence (LINF) emissions resulting from excitation by a new technology deep UV laser. Detection and identification is accomplished in less than 1ms. Standoff excitation of suspicious packages, vehicles, persons, and other objects that may contain hazardous materials is accomplished using wavelengths below 250nm where Raman and native fluorescence emissions occupy distinctly different wavelength regions. This enables simultaneous detection of RR and LINF emissions with no interferences. The sensor employs fused RR/LINF chemometric methods to extract the identity of targeted materials from background clutter. Photon Systems has demonstrated detection and identification of 100ng/cm2 of explosives materials at a distance of 1 meter using a sensor with 3.8 cm optical aperture. Expansion of the optical aperture to 38 cm in a lantern-sized sensor will enable similar detection and identification of CBE materials at standoff distances of 10 meters. As a result of excitation and detection in the deep UV and the use of a gated detection system, the sensor is solar blind and can operate in full daylight conditions.

Automatic building identification under bomb damage conditions

NASA Astrophysics Data System (ADS)

Woodley, Robert; Noll, Warren; Barker, Joseph; Wunsch, Donald C., II

2009-05-01

Given the vast amount of image intelligence utilized in support of planning and executing military operations, a passive automated image processing capability for target identification is urgently required. Furthermore, transmitting large image streams from remote locations would quickly use available band width (BW) precipitating the need for processing to occur at the sensor location. This paper addresses the problem of automatic target recognition for battle damage assessment (BDA). We utilize an Adaptive Resonance Theory approach to cluster templates of target buildings. The results show that the network successfully classifies targets from non-targets in a virtual test bed environment.

An Efficient Approach to Evaluate Reporter Ion Behavior from MALDI-MS/MS Data for Quantification Studies using Isobaric Tags

PubMed Central

Cologna, Stephanie M.; Crutchfield, Christopher A.; Searle, Brian C.; Blank, Paul S.; Toth, Cynthia L.; Ely, Alexa M.; Picache, Jaqueline A.; Backlund, Peter S.; Wassif, Christopher A.; Porter, Forbes D.; Yergey, Alfred L.

2017-01-01

Protein quantification, identification and abundance determination are important aspects of proteome characterization and are crucial in understanding biological mechanisms and human diseases. Different strategies are available to quantify proteins using mass spectrometric detection, and most are performed at the peptide level and include both targeted and un-targeted methodologies. Discovery-based or un-targeted approaches oftentimes use covalent tagging strategies (i.e., iTRAQ®, TMT™) where reporter ion signals collected in the tandem MS experiment are used for quantification. Herein we investigate the behavior of the iTRAQ 8-plex chemistry using MALDI-TOF/TOF instrumentation. The experimental design and data analysis approach described is simple and straightforward, which allows researchers to optimize data collection and proper analysis within a laboratory. iTRAQ reporter ion signals were normalized within each spectrum to remove peptide biases. An advantage of this approach is that missing reporter ion values can be accepted for purposes of protein identification and quantification with the need for ANOVA analysis. We investigate the distribution of reporter ion peak areas in an equimolar system and a mock biological system and provide recommendations for establishing fold-change cutoff values at the peptide level for iTRAQ datasets. These data provide a unique dataset available to the community for informatics training and analysis. PMID:26288259

Trace detection of specific viable bacteria using tetracysteine-tagged bacteriophages.

PubMed

Wu, Lina; Luan, Tian; Yang, Xiaoting; Wang, Shuo; Zheng, Yan; Huang, Tianxun; Zhu, Shaobin; Yan, Xiaomei

2014-01-07

Advanced methods are urgently needed to determine the identity and viability of trace amounts of pathogenic bacteria in a short time. Existing approaches either fall short in the accurate assessment of microbial viability or lack specificity in bacterial identification. Bacteriophages (or phages for short) are viruses that exclusively infect bacterial host cells with high specificity. As phages infect and replicate only in living bacterial hosts, here we exploit the strategy of using tetracysteine (TC)-tagged phage in combination with biarsenical dye to the discriminative detection of viable target bacteria from dead target cells and other viable but nontarget bacterial cells. Using recombinant M13KE-TC phage and Escherichia coli ER2738 as a model system, distinct differentiation between individual viable target cells from dead target cells was demonstrated by flow cytometry and fluorescence microscopy. As few as 1% viable E. coli ER2738 can be accurately quantified in a mix with dead E. coli ER2738 by flow cytometry. With fluorescence microscopic measurement, specific detection of as rare as 1 cfu/mL original viable target bacteria was achieved in the presence of a large excess of dead target cells and other viable but nontarget bacterial cells in 40 mL artificially contaminated drinking water sample in less than 3 h. This TC-phage-FlAsH approach is sensitive, specific, rapid, and simple, and thus shows great potential in water safety monitoring, health surveillance, and clinical diagnosis of which trace detection and identification of viable bacterial pathogens is highly demanded.

[Development and application of reference materials containing mixed degradation products of amoxicillin and ampicillin].

PubMed

Li, Wei; Zhang, Wei-Qing; Li, Xiang; Hu, Chang-Qin

2014-09-01

Reference materials containing mixed degradation products of amoxicillin and ampicillin were developed after optimization of preparation processes. The target impurities were obtained by controlled stress testing, and each major component was identified with HPLC-MS and compared with single traceable reference standard each. The developed reference materials were applied to system suitability test for verifying HPLC system performed in accordance with set forth in China Pharmacopeia and identification of major impurities in samples based on retention and spectra information, which have advantages over the methods put forth in foreign pharmacopoeias. The development and application of the reference materials offer an effective way for rapid identification of impurities in chromatograms, and provide references for analyzing source of impurities and evaluation of drug quality.

In situ damage monitoring in vibration mechanics: diagnostics and predictive maintenance

NASA Astrophysics Data System (ADS)

Basseville, M.; Benveniste, A.; Gach-Devauchelle, B.; Goursat, M.; Bonnecase, D.; Dorey, P.; Prevosto, M.; Olagnon, M.

1993-09-01

A system identification approach is presented for damage monitoring in vibration mechanics. Identification, detection, and diagnostics are performed using accelerometer measurements from the system at work so that the excitation is not controlled, usually not observed and may involve turbulent phenomena. Targeted applications include power engineering (rotating machines, core and pipes of nuclear power plants), civil engineering (large buildings subject to hurricanes or earthquakes, bridges, dams, offshore structures), aeronautics (wings and other structures subject to strength), automobile, rail transportation etc. The method is illustrated by a laboratory example, and the results of 3 years industrial usage. This paper is a progress report on a 10 year project involving three people almost permanently. We describe here the whole approach but omit the technical details which are available in previous papers.

Evaluation of Waveform Structure Features on Time Domain Target Recognition under Cross Polarization

NASA Astrophysics Data System (ADS)

Selver, M. A.; Seçmen, M.; Zoral, E. Y.

2016-08-01

Classification of aircraft targets from scattered electromagnetic waves is a challenging application, which suffers from aspect angle dependency. In order to eliminate the adverse effects of aspect angle, various strategies were developed including the techniques that rely on extraction of several features and design of suitable classification systems to process them. Recently, a hierarchical method, which uses features that take advantage of waveform structure of the scattered signals, is introduced and shown to have effective results. However, this approach has been applied to the special cases that consider only a single planar component of electric field that cause no-cross polarization at the observation point. In this study, two small scale aircraft models, Boeing-747 and DC-10, are selected as the targets and various polarizations are used to analyse the cross-polarization effects on system performance of the aforementioned method. The results reveal the advantages and the shortcomings of using waveform structures in time-domain target identification.

A Statistics-based Platform for Quantitative N-terminome Analysis and Identification of Protease Cleavage Products*

PubMed Central

auf dem Keller, Ulrich; Prudova, Anna; Gioia, Magda; Butler, Georgina S.; Overall, Christopher M.

2010-01-01

Terminal amine isotopic labeling of substrates (TAILS), our recently introduced platform for quantitative N-terminome analysis, enables wide dynamic range identification of original mature protein N-termini and protease cleavage products. Modifying TAILS by use of isobaric tag for relative and absolute quantification (iTRAQ)-like labels for quantification together with a robust statistical classifier derived from experimental protease cleavage data, we report reliable and statistically valid identification of proteolytic events in complex biological systems in MS2 mode. The statistical classifier is supported by a novel parameter evaluating ion intensity-dependent quantification confidences of single peptide quantifications, the quantification confidence factor (QCF). Furthermore, the isoform assignment score (IAS) is introduced, a new scoring system for the evaluation of single peptide-to-protein assignments based on high confidence protein identifications in the same sample prior to negative selection enrichment of N-terminal peptides. By these approaches, we identified and validated, in addition to known substrates, low abundance novel bioactive MMP-2 targets including the plasminogen receptor S100A10 (p11) and the proinflammatory cytokine proEMAP/p43 that were previously undescribed. PMID:20305283

20180318 - Structure identification by Mass Spectrometry Non-Targeted Analysis using the US EPA’s CompTox Chemistry Dashboard (ACS Spring)

EPA Science Inventory

Identification of unknowns in mass spectrometry based non-targeted analyses (NTA) requires the integration of complementary pieces of data to arrive at a confident, consensus structure. Researchers use chemical reference databases, spectral matching, fragment prediction tools, r...

Identification of NPM and DDX5 as Therapeutic Targets in TSC

DTIC Science & Technology

2017-12-01

Individuals with TSC develop benign tumors in multiple organs, including the retina, skin, lung, kidney and brain. The identification of valid targets in TSC...individuals. Individuals with TSC develop benign tumors in multiple organs, including the retina, skin, lung, kidney and brain. However, these lesions can

The Influence of Attention and Target Identification on Saccadic Eye Movements Depends on Prior Target Location

PubMed Central

Hardwick, David R.; Cutmore, Timothy R. H.; Hine, Trevor J.

2014-01-01

Saccadic latency is reduced by a temporal gap between fixation point and target, by identification of a target feature, and by movement in a new direction (inhibition of saccadic return, ISR). A simple additive model was compared with a shared resources model that predicts a three-way interaction. Twenty naïve participants made horizontal saccades to targets left and right of fixation in a randomised block design. There was a significant three-way interaction among the factors on saccade latency. This was revealed in a two-way interaction between feature identification and the gap versus no gap factor which was only apparent when the saccade was in the same direction as the previous saccade. No interaction was apparent when the saccade was in the opposite direction. This result supports an attentional inhibitory effect that is present during ISR to a previous location which is only partly released by the facilitative effect of feature identification and gap. Together, anticipatory error data and saccade latency interactions suggest a source of ISR at a higher level of attention, possibly localised in the dorsolateral prefrontal cortex and involving tonic activation. PMID:24719754

OncDRS: An integrative clinical and genomic data platform for enabling translational research and precision medicine

PubMed Central

Orechia, John; Pathak, Ameet; Shi, Yunling; Nawani, Aniket; Belozerov, Andrey; Fontes, Caitlin; Lakhiani, Camille; Jawale, Chetan; Patel, Chetansharan; Quinn, Daniel; Botvinnik, Dmitry; Mei, Eddie; Cotter, Elizabeth; Byleckie, James; Ullman-Cullere, Mollie; Chhetri, Padam; Chalasani, Poornima; Karnam, Purushotham; Beaudoin, Ronald; Sahu, Sandeep; Belozerova, Yelena; Mathew, Jomol P.

2015-01-01

We live in the genomic era of medicine, where a patient's genomic/molecular data is becoming increasingly important for disease diagnosis, identification of targeted therapy, and risk assessment for adverse reactions. However, decoding the genomic test results and integrating it with clinical data for retrospective studies and cohort identification for prospective clinical trials is still a challenging task. In order to overcome these barriers, we developed an overarching enterprise informatics framework for translational research and personalized medicine called Synergistic Patient and Research Knowledge Systems (SPARKS) and a suite of tools called Oncology Data Retrieval Systems (OncDRS). OncDRS enables seamless data integration, secure and self-navigated query and extraction of clinical and genomic data from heterogeneous sources. Within a year of release, the system has facilitated more than 1500 research queries and has delivered data for more than 50 research studies. PMID:27054074

Angiotensins as therapeutic targets beyond heart disease.

PubMed

Passos-Silva, Danielle Gomes; Brandan, Enrique; Santos, Robson Augusto Souza

2015-05-01

The renin-angiotensin system (RAS) plays a pivotal role in cardiovascular and hydro-electrolyte homeostasis. Blockade of the RAS as a therapeutic strategy for treating hypertension and related cardiovascular diseases is well established. However, actions of the RAS go far beyond the targets initially described. In this regard, the recent identification of novel components of the RAS, including angiotensin-(1-7) [Ang-(1-7)], Ang-(1-9), and alamandine, have opened new possibilities for interfering with the development and manifestations of cardiovascular and non-cardiovascular diseases. In this article, we briefly review novel targets for angiotensins and its therapeutic implications in diverse areas, including cancer, inflammation, and glaucoma. Copyright © 2015 Elsevier Ltd. All rights reserved.

Molecular mechanisms of floral organ specification by MADS domain proteins.

PubMed

Yan, Wenhao; Chen, Dijun; Kaufmann, Kerstin

2016-02-01

Flower development is a model system to understand organ specification in plants. The identities of different types of floral organs are specified by homeotic MADS transcription factors that interact in a combinatorial fashion. Systematic identification of DNA-binding sites and target genes of these key regulators show that they have shared and unique sets of target genes. DNA binding by MADS proteins is not based on 'simple' recognition of a specific DNA sequence, but depends on DNA structure and combinatorial interactions. Homeotic MADS proteins regulate gene expression via alternative mechanisms, one of which may be to modulate chromatin structure and accessibility in their target gene promoters. Copyright © 2015 Elsevier Ltd. All rights reserved.

The IUE Science Operations Ground System

NASA Technical Reports Server (NTRS)

Pitts, Ronald E.; Arquilla, Richard

1994-01-01

The International Ultraviolet Explorer (IUE) Science Operations System provides full realtime operations capabilities and support to the operations staff and astronomer users. The components of this very diverse and extremely flexible hardware and software system have played a major role in maintaining the scientific efficiency and productivity of the IUE. The software provides the staff and user with all the tools necessary for pre-visit and real-time planning and operations analysis for any day of the year. Examples of such tools include the effects of spacecraft constraints on target availability, maneuver times between targets, availability of guide stars, target identification, coordinate transforms, e-mail transfer of Observatory forms and messages, and quick-look analysis of image data. Most of this extensive software package can also be accessed remotely by individual users for information, scheduling of shifts, pre-visit planning, and actual observing program execution. Astronomers, with a modest investment in hardware and software, may establish remote observing sites. We currently have over 20 such sites in our remote observers' network.

Research and development on performance models of thermal imaging systems

NASA Astrophysics Data System (ADS)

Wang, Ji-hui; Jin, Wei-qi; Wang, Xia; Cheng, Yi-nan

2009-07-01

Traditional ACQUIRE models perform the discrimination tasks of detection (target orientation, recognition and identification) for military target based upon minimum resolvable temperature difference (MRTD) and Johnson criteria for thermal imaging systems (TIS). Johnson criteria is generally pessimistic for performance predict of sampled imager with the development of focal plane array (FPA) detectors and digital image process technology. Triangle orientation discrimination threshold (TOD) model, minimum temperature difference perceived (MTDP)/ thermal range model (TRM3) Model and target task performance (TTP) metric have been developed to predict the performance of sampled imager, especially TTP metric can provides better accuracy than the Johnson criteria. In this paper, the performance models above are described; channel width metrics have been presented to describe the synthesis performance including modulate translate function (MTF) channel width for high signal noise to ration (SNR) optoelectronic imaging systems and MRTD channel width for low SNR TIS; the under resolvable questions for performance assessment of TIS are indicated; last, the development direction of performance models for TIS are discussed.

A robust close-range photogrammetric target extraction algorithm for size and type variant targets

NASA Astrophysics Data System (ADS)

Nyarko, Kofi; Thomas, Clayton; Torres, Gilbert

2016-05-01

The Photo-G program conducted by Naval Air Systems Command at the Atlantic Test Range in Patuxent River, Maryland, uses photogrammetric analysis of large amounts of real-world imagery to characterize the motion of objects in a 3-D scene. Current approaches involve several independent processes including target acquisition, target identification, 2-D tracking of image features, and 3-D kinematic state estimation. Each process has its own inherent complications and corresponding degrees of both human intervention and computational complexity. One approach being explored for automated target acquisition relies on exploiting the pixel intensity distributions of photogrammetric targets, which tend to be patterns with bimodal intensity distributions. The bimodal distribution partitioning algorithm utilizes this distribution to automatically deconstruct a video frame into regions of interest (ROI) that are merged and expanded to target boundaries, from which ROI centroids are extracted to mark target acquisition points. This process has proved to be scale, position and orientation invariant, as well as fairly insensitive to global uniform intensity disparities.

Graphene-based aptamer logic gates and their application to multiplex detection.

PubMed

Wang, Li; Zhu, Jinbo; Han, Lei; Jin, Lihua; Zhu, Chengzhou; Wang, Erkang; Dong, Shaojun

2012-08-28

In this work, a GO/aptamer system was constructed to create multiplex logic operations and enable sensing of multiplex targets. 6-Carboxyfluorescein (FAM)-labeled adenosine triphosphate binding aptamer (ABA) and FAM-labeled thrombin binding aptamer (TBA) were first adsorbed onto graphene oxide (GO) to form a GO/aptamer complex, leading to the quenching of the fluorescence of FAM. We demonstrated that the unique GO/aptamer interaction and the specific aptamer-target recognition in the target/GO/aptamer system were programmable and could be utilized to regulate the fluorescence of FAM via OR and INHIBIT logic gates. The fluorescence changed according to different input combinations, and the integration of OR and INHIBIT logic gates provided an interesting approach for logic sensing applications where multiple target molecules were present. High-throughput fluorescence imagings that enabled the simultaneous processing of many samples by using the combinatorial logic gates were realized. The developed logic gates may find applications in further development of DNA circuits and advanced sensors for the identification of multiple targets in complex chemical environments.

Study of time-reversal-based signal processing applied to polarimetric GPR detection of elongated targets

NASA Astrophysics Data System (ADS)

Santos, Vinicius Rafael N.; Teixeira, Fernando L.

2017-04-01

Ground penetrating radar (GPR) is a useful sensing modality for mapping and identification of underground infrastructure networks, such as metal and concrete pipes (gas, water or sewer), phone conduits or cables, and other buried objects. Due to the polarization-dependent response of typical targets, it is of interest to investigate the optimum antenna arrangement and/or combination of arrangements that maximize the detection and classification capabilities of polarimetric GPR imaging systems. Here, we provide a preliminary study of time-reversal-based techniques applied to target detection by GPR utilizing different relative orientations of linear-polarized antenna elements (with respect to each other, as well as to the targets). We modeled three different pipe materials (metallic, plastic and concrete) and GPR systems operating at center frequencies of 100 MHz and 200 MHz. Full-wave numerical simulations are adopted to account for mutual coupling between targets. This type of assessment study may contribute to the improvement of GPR data interpretation of infrastructure networks in urban area surveys and in other engineering studies.

The star identification, pointing and tracking system of UVSTAR, an attached payload instrument system for the Shuttle Hitchhiker-M platform

NASA Technical Reports Server (NTRS)

Decarlo, Francesco; Stalio, Roberto; Trampus, Paolo; Broadfoot, A. Lyle; Sandel, Bill R.; Sicuranza, Giovanni

1993-01-01

We describe an algorithm for star identification and pointing/tracking of a spaceborne electro-optical system and simulation analyses to test the algorithm. The algorithm will be implemented in the guiding system of UVSTAR, a spectrographic telescope for observations of astronomical and planetary sources operating in the 500-1250 A waveband at approximately 1 A resolution. The experiment is an attached payload and will fly as a Hitchhiker-M payload on the Shuttle. UVSTAR includes capabilities for independent target acquisition and tracking. The spectrograph package has internal gimbals that allow angular movement of plus or minus 3 deg from the central position. Rotation about the azimuth axis (parallel to the Shuttle z axis) and elevation axis (parallel to the Shuttle x axis) will actively position the field of view to center the target of interest in the fields of the spectrographs. The algorithm is based on an on-board catalog of stars. To identify star fields, the algorithm compares the positions of stars recorded by the guiding imager to positions computed from the on-board catalog. When the field has been identified, its position within the guiding imager field of view can be used to compute the pointing corrections necessary to point to a target of interest. In tracking mode, the software uses the past history to predict the quasi-periodic attitude control motions of the shuttle and sends pointing commands to cancel the motion and stabilize UVSTAR on the target. The guiding imager (guider) will have an 80-mm focal length and f/1.4 optics giving a field of view of 6 deg x 4.5 deg using a 385 x 288 pixel intensified CCD. It will be capable of providing high accuracy (better than 2 arc-sec) attitude determination from coarse (6 deg x 4.5 deg) initial knowledge of the pointing direction; and of pointing toward the target. It will also be capable of tracking at the same high accuracy with a processing time of less than a few hundredths of a second.

Summary of tracking and identification methods

NASA Astrophysics Data System (ADS)

Blasch, Erik; Yang, Chun; Kadar, Ivan

2014-06-01

Over the last two decades, many solutions have arisen to combine target tracking estimation with classification methods. Target tracking includes developments from linear to non-linear and Gaussian to non-Gaussian processing. Pattern recognition includes detection, classification, recognition, and identification methods. Integrating tracking and pattern recognition has resulted in numerous approaches and this paper seeks to organize the various approaches. We discuss the terminology so as to have a common framework for various standards such as the NATO STANAG 4162 - Identification Data Combining Process. In a use case, we provide a comparative example highlighting that location information (as an example) with additional mission objectives from geographical, human, social, cultural, and behavioral modeling is needed to determine identification as classification alone does not allow determining identification or intent.

Discerning cultural identification from a thinly sliced behavioral sample.

PubMed

Hamamura, Takeshi; Li, Liman Man Wai

2012-12-01

This research examined whether individual differences in cultural identification can be discerned at zero acquaintance. This issue was examined in Hong Kong, where the idiosyncrasy of cultural identification is a salient social-psychological issue. The participants were able to perceive accurately the targets' identification with Western culture from a video clip and from a still image. Findings also indicated that a stereotype of Western cultural identity (i.e., extraversion and particular hairstyle) facilitated these perceptions. Specifically, (a) the participants with a stronger stereotype were more accurate in perceiving Western cultural identification, (b) the targets who were experimentally manipulated to appear extraverted were rated as more strongly identifying with Western culture, and (c) the participants relatively unfamiliar with these stereotypes did not correctly perceive Western cultural identification. Implications of these findings on research on multiculturalism are also discussed.

Snapshot spectral and polarimetric imaging; target identification with multispectral video

NASA Astrophysics Data System (ADS)

Bartlett, Brent D.; Rodriguez, Mikel D.

2013-05-01

As the number of pixels continue to grow in consumer and scientific imaging devices, it has become feasible to collect the incident light field. In this paper, an imaging device developed around light field imaging is used to collect multispectral and polarimetric imagery in a snapshot fashion. The sensor is described and a video data set is shown highlighting the advantage of snapshot spectral imaging. Several novel computer vision approaches are applied to the video cubes to perform scene characterization and target identification. It is shown how the addition of spectral and polarimetric data to the video stream allows for multi-target identification and tracking not possible with traditional RGB video collection.

DARPA super resolution vision system (SRVS) robust turbulence data collection and analysis

NASA Astrophysics Data System (ADS)

Espinola, Richard L.; Leonard, Kevin R.; Thompson, Roger; Tofsted, David; D'Arcy, Sean

2014-05-01

Atmospheric turbulence degrades the range performance of military imaging systems, specifically those intended for long range, ground-to-ground target identification. The recent Defense Advanced Research Projects Agency (DARPA) Super Resolution Vision System (SRVS) program developed novel post-processing system components to mitigate turbulence effects on visible and infrared sensor systems. As part of the program, the US Army RDECOM CERDEC NVESD and the US Army Research Laboratory Computational & Information Sciences Directorate (CISD) collaborated on a field collection and atmospheric characterization of a two-handed weapon identification dataset through a diurnal cycle for a variety of ranges and sensor systems. The robust dataset is useful in developing new models and simulations of turbulence, as well for providing as a standard baseline for comparison of sensor systems in the presence of turbulence degradation and mitigation. In this paper, we describe the field collection and atmospheric characterization and present the robust dataset to the defense, sensing, and security community. In addition, we present an expanded model validation of turbulence degradation using the field collected video sequences.

Neurological Disease in Lupus: Toward a Personalized Medicine Approach.

PubMed

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P J

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials.

Concealed identification symbols and nondestructive determination of the identification symbols

DOEpatents

Nance, Thomas A.; Gibbs, Kenneth M.

2014-09-16

The concealing of one or more identification symbols into a target object and the subsequent determination or reading of such symbols through non-destructive testing is described. The symbols can be concealed in a manner so that they are not visible to the human eye and/or cannot be readily revealed to the human eye without damage or destruction of the target object. The identification symbols can be determined after concealment by e.g., the compilation of multiple X-ray images. As such, the present invention can also provide e.g., a deterrent to theft and the recovery of lost or stolen objects.

Structure identification for Non-Targeted Analytical Chemistry using the US EPA’s CompTox Chemistry Dashboard (ACS 2017 Fall meeting 3 of 3)

EPA Science Inventory

Identification of unknowns in non-targeted analyses (NTA) requires the integration of complementary data types to generate a confident consensus structure. Researchers use a variety of data and tools (e.g., chemical reference databases, spectral matching, fragment prediction too...

Automated intelligent video surveillance system for ships

NASA Astrophysics Data System (ADS)

Wei, Hai; Nguyen, Hieu; Ramu, Prakash; Raju, Chaitanya; Liu, Xiaoqing; Yadegar, Jacob

2009-05-01

To protect naval and commercial ships from attack by terrorists and pirates, it is important to have automatic surveillance systems able to detect, identify, track and alert the crew on small watercrafts that might pursue malicious intentions, while ruling out non-threat entities. Radar systems have limitations on the minimum detectable range and lack high-level classification power. In this paper, we present an innovative Automated Intelligent Video Surveillance System for Ships (AIVS3) as a vision-based solution for ship security. Capitalizing on advanced computer vision algorithms and practical machine learning methodologies, the developed AIVS3 is not only capable of efficiently and robustly detecting, classifying, and tracking various maritime targets, but also able to fuse heterogeneous target information to interpret scene activities, associate targets with levels of threat, and issue the corresponding alerts/recommendations to the man-in- the-loop (MITL). AIVS3 has been tested in various maritime scenarios and shown accurate and effective threat detection performance. By reducing the reliance on human eyes to monitor cluttered scenes, AIVS3 will save the manpower while increasing the accuracy in detection and identification of asymmetric attacks for ship protection.

The Role of the Insulin/IGF System in Cancer: Lessons Learned from Clinical Trials and the Energy Balance-Cancer Link

PubMed Central

Bowers, Laura W.; Rossi, Emily L.; O’Flanagan, Ciara H.; deGraffenried, Linda A.; Hursting, Stephen D.

2015-01-01

Numerous epidemiological and pre-clinical studies have demonstrated that the insulin/insulin-like growth factor (IGF) system plays a key role in the development and progression of several types of cancer. Insulin/IGF signaling, in cooperation with chronic low-grade inflammation, is also an important contributor to the cancer-promoting effects of obesity. However, clinical trials for drugs targeting different components of this system have produced largely disappointing results, possibly due to the lack of predictive biomarker use and problems with the design of combination therapy regimens. With careful attention to the identification of likely patient responders and optimal drug combinations, the outcome of future trials may be improved. Given that insulin/IGF signaling is known to contribute to obesity-associated cancer, further investigation regarding the efficacy of drugs targeting this system and its downstream effectors in the obese patient population is warranted. PMID:26029167

Identification of FGF-dependent genes in the Drosophila tracheal system.

PubMed

Stahl, Markus; Schuh, Reinhard; Adryan, Boris

2007-01-01

The embryonic development of the tracheal system of the fruit fly Drosophila provides a paradigm for genetic studies of branching morphogenesis. Efforts of many laboratories have identified Branchless (Bnl, a fibroblast growth factor homologue) and Breathless (Btl, the receptor homologue) as crucial factors at many stages of tracheal system development. The downstream targets of the Bnl/Btl signalling cascade, however, remain mostly unknown. Misexpression of the bnl gene results in specific tracheal phenotypes that lead to larval death. We characterised the transcriptional profiles of targeted over-expression of bnl in the embryonic trachea and of loss-of-function bnl(P1) mutant embryos. Gene expression data was mapped to high-throughput in situ hybridisation based ImaGO-annotation. Thus, we identified and confirmed by quantitative PCR 13 Bnl-dependent genes that are expressed in cells within and outside of the tracheal system.

Wavefront-Guided Versus Wavefront-Optimized Photorefractive Keratectomy: Visual and Military Task Performance.

PubMed

Ryan, Denise S; Sia, Rose K; Stutzman, Richard D; Pasternak, Joseph F; Howard, Robin S; Howell, Christopher L; Maurer, Tana; Torres, Mark F; Bower, Kraig S

2017-01-01

To compare visual performance, marksmanship performance, and threshold target identification following wavefront-guided (WFG) versus wavefront-optimized (WFO) photorefractive keratectomy (PRK). In this prospective, randomized clinical trial, active duty U.S. military Soldiers, age 21 or over, electing to undergo PRK were randomized to undergo WFG (n = 27) or WFO (n = 27) PRK for myopia or myopic astigmatism. Binocular visual performance was assessed preoperatively and 1, 3, and 6 months postoperatively: Super Vision Test high contrast, Super Vision Test contrast sensitivity (CS), and 25% contrast acuity with night vision goggle filter. CS function was generated testing at five spatial frequencies. Marksmanship performance in low light conditions was evaluated in a firing tunnel. Target detection and identification performance was tested for probability of identification of varying target sets and probability of detection of humans in cluttered environments. Visual performance, CS function, marksmanship, and threshold target identification demonstrated no statistically significant differences over time between the two treatments. Exploratory regression analysis of firing range tasks at 6 months showed no significant differences or correlations between procedures. Regression analysis of vehicle and handheld probability of identification showed a significant association with pretreatment performance. Both WFG and WFO PRK results translate to excellent and comparable visual and military performance. Reprint & Copyright © 2017 Association of Military Surgeons of the U.S.

Research on photodiode detector-based spatial transient light detection and processing system

NASA Astrophysics Data System (ADS)

Liu, Meiying; Wang, Hu; Liu, Yang; Zhao, Hui; Nan, Meng

2016-10-01

In order to realize real-time signal identification and processing of spatial transient light, the features and the energy of the captured target light signal are first described and quantitatively calculated. Considering that the transient light signal has random occurrence, a short duration and an evident beginning and ending, a photodiode detector based spatial transient light detection and processing system is proposed and designed in this paper. This system has a large field of view and is used to realize non-imaging energy detection of random, transient and weak point target under complex background of spatial environment. Weak signal extraction under strong background is difficult. In this paper, considering that the background signal changes slowly and the target signal changes quickly, filter is adopted for signal's background subtraction. A variable speed sampling is realized by the way of sampling data points with a gradually increased interval. The two dilemmas that real-time processing of large amount of data and power consumption required by the large amount of data needed to be stored are solved. The test results with self-made simulative signal demonstrate the effectiveness of the design scheme. The practical system could be operated reliably. The detection and processing of the target signal under the strong sunlight background was realized. The results indicate that the system can realize real-time detection of target signal's characteristic waveform and monitor the system working parameters. The prototype design could be used in a variety of engineering applications.

Data fusion approach to threat assessment for radar resources management

NASA Astrophysics Data System (ADS)

Komorniczak, Wojciech; Pietrasinski, Jerzy; Solaiman, Basel

2002-03-01

The paper deals with the problem of the multifunction radar resources management. The problem consists of target/tasks ranking and tasks scheduling. The paper is focused on the target ranking, with the data fusion approach. The data from the radar (object's velocity, range, altitude, direction etc.), IFF system (Identification Friend or Foe) and ESM system (Electronic Support Measures - information concerning threat's electro - magnetic activities) is used to decide of the importance assignment for each detected target. The main problem consists of the multiplicity of various types of the input information. The information from the radar is of the probabilistic or ambiguous imperfection type and the IFF information is of evidential type. To take the advantage of these information sources the advanced data fusion system is necessary. The system should deal with the following situations: fusion of the evidential and fuzzy information, fusion of the evidential information and a'priori information. The paper describes the system which fuses the fuzzy and the evidential information without previous change to the same type of information. It is also described the proposal of using of the dynamic fuzzy qualifiers. The paper shows the results of the preliminary system's tests.

Plant microRNA-Target Interaction Identification Model Based on the Integration of Prediction Tools and Support Vector Machine

PubMed Central

Meng, Jun; Shi, Lin; Luan, Yushi

2014-01-01

Background 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. Results 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. Conclusions 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. PMID:25051153

Rapid Identification of Mycobacteria and Drug-Resistant Mycobacterium tuberculosis by Use of a Single Multiplex PCR and DNA Sequencing

PubMed Central

Pérez-Osorio, Ailyn C.; Boyle, David S.; Ingham, Zachary K.; Ostash, Alla; Gautom, Romesh K.; Colombel, Craig; Houze, Yolanda

2012-01-01

Tuberculosis (TB) remains a significant global health problem for which rapid diagnosis is critical to both treatment and control. This report describes a multiplex PCR method, the Mycobacterial IDentification and Drug Resistance Screen (MID-DRS) assay, which allows identification of members of the Mycobacterium tuberculosis complex (MTBC) and the simultaneous amplification of targets for sequencing-based drug resistance screening of rifampin-resistant (rifampinr), isoniazidr, and pyrazinamider TB. Additionally, the same multiplex reaction amplifies a specific 16S rRNA gene target for rapid identification of M. avium complex (MAC) and a region of the heat shock protein 65 gene (hsp65) for further DNA sequencing-based confirmation or identification of other mycobacterial species. Comparison of preliminary results generated with MID-DRS versus culture-based methods for a total of 188 bacterial isolates demonstrated MID-DRS sensitivity and specificity as 100% and 96.8% for MTBC identification; 100% and 98.3% for MAC identification; 97.4% and 98.7% for rifampinr TB identification; 60.6% and 100% for isoniazidr TB identification; and 75.0% and 98.1% for pyrazinamider TB identification. The performance of the MID-DRS was also tested on acid-fast-bacterium (AFB)-positive clinical specimens, resulting in sensitivity and specificity of 100% and 78.6% for detection of MTBC and 100% and 97.8% for detection of MAC. In conclusion, use of the MID-DRS reduces the time necessary for initial identification and drug resistance screening of TB specimens to as little as 2 days. Since all targets needed for completing the assay are included in a single PCR amplification step, assay costs, preparation time, and risks due to user errors are also reduced. PMID:22162548

Bombing Target Identification from Limited Transect Data

DOE Office of Scientific and Technical Information (OSTI.GOV)

Roberts, Barry L.; Hathaway, John E.; Pulsipher, Brent A.

2006-08-07

A series of sensor data combined with geostatistical techniques were used to determine likely target areas for a historic military aerial bombing range. Primary data consisted of magnetic anomaly information from limited magnetometer transects across the site. Secondary data included airborne LIDAR, orthophotography, and other general site characterization information. Identification of likely target areas relied primarily upon kriging estimates of magnetic anomaly densities across the site. Secondary information, such as impact crater locations, was used to refine the boundary delineations.

Identification of Lactobacillus from the Saliva of Adult Patients with Caries Using Matrix-Assisted Laser Desorption/Ionization Time-Of-Flight Mass Spectrometry

PubMed Central

Ma, Qingwei; Song, Yeqing; Zhang, Qian; Wang, Xiaoyan; Chen, Feng

2014-01-01

Matrix-assisted laser desorption/ionization (MALDI) time-of-flight (TOF) mass spectrometry (MS) has been presented as a superior method for the detection of microorganisms in body fluid samples (e.g., blood, saliva, pus, etc.) However, the performance of MALDI-TOF MS in routine identification of caries-related Lactobacillus isolates from saliva of adult patients with caries has not been determined. In the present study, we introduced a new MALDI-TOF MS system for identification of lactobacilli. Saliva samples were collected from 120 subjects with caries. Bacteria were isolated and cultured, and each isolate was identified by both 16S rRNA sequencing and MALDI-TOF MS. The identification results obtained by MALDI-TOF MS were concordant at the genus level with those of conventional 16S rRNA-based sequencing for 88.6% of lactobacilli (62/70) and 95.5% of non-lactobacilli (21/22). Up to 96 results could be obtained in parallel on a single MALDI target, suggesting that this is a reliable high-throughput approach for routine identification of lactobacilli. However, additional reference strains are necessary to increase the sensitivity and specificity of species-level identification. PMID:25166027

MALDI-TOF MS identification of anaerobic bacteria: assessment of pre-analytical variables and specimen preparation techniques.

PubMed

Hsu, Yen-Michael S; Burnham, Carey-Ann D

2014-06-01

Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) has emerged as a tool for identifying clinically relevant anaerobes. We evaluated the analytical performance characteristics of the Bruker Microflex with Biotyper 3.0 software system for identification of anaerobes and examined the impact of direct formic acid (FA) treatment and other pre-analytical factors on MALDI-TOF MS performance. A collection of 101 anaerobic bacteria were evaluated, including Clostridium spp., Propionibacterium spp., Fusobacterium spp., Bacteroides spp., and other anaerobic bacterial of clinical relevance. The results of our study indicate that an on-target extraction with 100% FA improves the rate of accurate identification without introducing misidentification (P<0.05). In addition, we modify the reporting cutoffs for the Biotyper "score" yielding acceptable identification. We found that a score of ≥1.700 can maximize the rate of identification. Of interest, MALDI-TOF MS can correctly identify anaerobes grown in suboptimal conditions, such as on selective culture media and following oxygen exposure. In conclusion, we report on a number of simple and cost-effective pre- and post-analytical modifications could enhance MALDI-TOF MS identification for anaerobic bacteria. Copyright © 2014 Elsevier Inc. All rights reserved.

Molecular Identification of Adult and Juvenile Linyphiid and Theridiid Spiders in Alpine Glacier Foreland Communities

PubMed Central

Raso, Lorna; Sint, Daniela; Rief, Alexander; Kaufmann, Rüdiger; Traugott, Michael

2014-01-01

In glacier forelands spiders constitute a large proportion of the invertebrate community. Therefore, it is important to be able to determine the species that can be found in these areas. Linyphiid and theridiid spider identification is currently not possible in juvenile specimens using traditional morphological based methods, however, a large proportion of the population in these areas are usually juveniles. Molecular methods permit identification of species at different life stages, making juvenile identification possible. In this study we tested a molecular tool to identify the 10 most common species of Linyphiidae and Theridiidae found in three glacier foreland communities of the Austrian Alps. Two multiplex PCR systems were developed and over 90% of the 753 field-collected spiders were identified successfully. The species targeted were found to be common in all three valleys during the summer of 2010. A comparison between the molecular and morphological data showed that although there was a slight difference in the results, the overall outcome was the same independently of the identification method used. We believe the quick and reliable identification of the spiders via the multiplex PCR assays developed here will aid the study of these families in Alpine habitats. PMID:25050841

Hierarchical relaxation methods for multispectral pixel classification as applied to target identification

NASA Astrophysics Data System (ADS)

Cohen, E. A., Jr.

1985-02-01

This report provides insights into the approaches toward image modeling as applied to target detection. The approach is that of examining the energy in prescribed wave-bands which emanate from a target and correlating the emissions. Typically, one might be looking at two or three infrared bands, possibly together with several visual bands. The target is segmented, using both first and second order modeling, into a set of interesting components and these components are correlated so as to enhance the classification process. A Markov-type model is used to provide an a priori assessment of the spatial relationships among critical parts of the target, and a stochastic model using the output of an initial probabilistic labeling is invoked. The tradeoff between this stochastic model and the Markov model is then optimized to yield a best labeling for identification purposes. In an identification of friend or foe (IFF) context, this methodology could be of interest, for it provides the ingredients for such a higher level of understanding.

Target identification of small molecules based on chemical biology approaches.

PubMed

Futamura, Yushi; Muroi, Makoto; Osada, Hiroyuki

2013-05-01

Recently, a phenotypic approach-screens that assess the effects of compounds on cells, tissues, or whole organisms-has been reconsidered and reintroduced as a complementary strategy of a target-based approach for drug discovery. Although the finding of novel bioactive compounds from large chemical libraries has become routine, the identification of their molecular targets is still a time-consuming and difficult process, making this step rate-limiting in drug development. In the last decade, we and other researchers have amassed a large amount of phenotypic data through progress in omics research and advances in instrumentation. Accordingly, the profiling methodologies using these datasets expertly have emerged to identify and validate specific molecular targets of drug candidates, attaining some progress in current drug discovery (e.g., eribulin). In the case of a compound that shows an unprecedented phenotype likely by inhibiting a first-in-class target, however, such phenotypic profiling is invalid. Under the circumstances, a photo-crosslinking affinity approach should be beneficial. In this review, we describe and summarize recent progress in both affinity-based (direct) and phenotypic profiling (indirect) approaches for chemical biology target identification.

Accurate and exact CNV identification from targeted high-throughput sequence data.

PubMed

Nord, Alex S; Lee, Ming; King, Mary-Claire; Walsh, Tom

2011-04-12

Massively parallel sequencing of barcoded DNA samples significantly increases screening efficiency for clinically important genes. Short read aligners are well suited to single nucleotide and indel detection. However, methods for CNV detection from targeted enrichment are lacking. We present a method combining coverage with map information for the identification of deletions and duplications in targeted sequence data. Sequencing data is first scanned for gains and losses using a comparison of normalized coverage data between samples. CNV calls are confirmed by testing for a signature of sequences that span the CNV breakpoint. With our method, CNVs can be identified regardless of whether breakpoints are within regions targeted for sequencing. For CNVs where at least one breakpoint is within targeted sequence, exact CNV breakpoints can be identified. In a test data set of 96 subjects sequenced across ~1 Mb genomic sequence using multiplexing technology, our method detected mutations as small as 31 bp, predicted quantitative copy count, and had a low false-positive rate. Application of this method allows for identification of gains and losses in targeted sequence data, providing comprehensive mutation screening when combined with a short read aligner.

Intelligent Image Analysis for Image-Guided Laser Hair Removal and Skin Therapy

NASA Technical Reports Server (NTRS)

Walker, Brian; Lu, Thomas; Chao, Tien-Hsin

2012-01-01

We present the development of advanced automatic target recognition (ATR) algorithms for the hair follicles identification in digital skin images to accurately direct the laser beam to remove the hair. The ATR system first performs a wavelet filtering to enhance the contrast of the hair features in the image. The system then extracts the unique features of the targets and sends the features to an Adaboost based classifier for training and recognition operations. The ATR system automatically classifies the hair, moles, or other skin lesion and provides the accurate coordinates of the intended hair follicle locations. The coordinates can be used to guide a scanning laser to focus energy only on the hair follicles. The intended benefit would be to protect the skin from unwanted laser exposure and to provide more effective skin therapy.

Harnessing CRISPR-Cas systems for bacterial genome editing.

PubMed

Selle, Kurt; Barrangou, Rodolphe

2015-04-01

Manipulation of genomic sequences facilitates the identification and characterization of key genetic determinants in the investigation of biological processes. Genome editing via clustered regularly interspaced short palindromic repeats (CRISPR)-CRISPR-associated (Cas) constitutes a next-generation method for programmable and high-throughput functional genomics. CRISPR-Cas systems are readily reprogrammed to induce sequence-specific DNA breaks at target loci, resulting in fixed mutations via host-dependent DNA repair mechanisms. Although bacterial genome editing is a relatively unexplored and underrepresented application of CRISPR-Cas systems, recent studies provide valuable insights for the widespread future implementation of this technology. This review summarizes recent progress in bacterial genome editing and identifies fundamental genetic and phenotypic outcomes of CRISPR targeting in bacteria, in the context of tool development, genome homeostasis, and DNA repair. Copyright © 2015 Elsevier Ltd. All rights reserved.

Modeling human target acquisition in ground-to-air weapon systems

NASA Technical Reports Server (NTRS)

Phatak, A. V.; Mohr, R. L.; Vikmanis, M.; Wei, K. C.

1982-01-01

The problems associated with formulating and validating mathematical models for describing and predicting human target acquisition response are considered. In particular, the extension of the human observer model to include the acquisition phase as well as the tracking segment is presented. Relationship of the Observer model structure to the more complex Standard Optimal Control model formulation and to the simpler Transfer Function/Noise representation is discussed. Problems pertinent to structural identifiability and the form of the parameterization are elucidated. A systematic approach toward the identification of the observer acquisition model parameters from ensemble tracking error data is presented.

A high-speed brain speller using steady-state visual evoked potentials.

PubMed

Nakanishi, Masaki; Wang, Yijun; Wang, Yu-Te; Mitsukura, Yasue; Jung, Tzyy-Ping

2014-09-01

Implementing a complex spelling program using a steady-state visual evoked potential (SSVEP)-based brain-computer interface (BCI) remains a challenge due to difficulties in stimulus presentation and target identification. This study aims to explore the feasibility of mixed frequency and phase coding in building a high-speed SSVEP speller with a computer monitor. A frequency and phase approximation approach was developed to eliminate the limitation of the number of targets caused by the monitor refresh rate, resulting in a speller comprising 32 flickers specified by eight frequencies (8-15 Hz with a 1 Hz interval) and four phases (0°, 90°, 180°, and 270°). A multi-channel approach incorporating Canonical Correlation Analysis (CCA) and SSVEP training data was proposed for target identification. In a simulated online experiment, at a spelling rate of 40 characters per minute, the system obtained an averaged information transfer rate (ITR) of 166.91 bits/min across 13 subjects with a maximum individual ITR of 192.26 bits/min, the highest ITR ever reported in electroencephalogram (EEG)-based BCIs. The results of this study demonstrate great potential of a high-speed SSVEP-based BCI in real-life applications.

Evaluation of species-specific PCR, Bruker MS, VITEK MS and the VITEK 2 system for the identification of clinical Enterococcus isolates.

PubMed

Fang, H; Ohlsson, A-K; Ullberg, M; Ozenci, V

2012-11-01

The purpose of this investigation was to compare the performance of species-specific polymerase chain reaction (PCR), matrix-assisted laser desorption/ionisation time-of-flight mass spectrometry (MALDI-TOF MS) and phenotypic identification systems for the identification of Enterococcus species. A total of 132 clinical isolates were investigated by the following: (1) a multiplex real-time PCR assay targeting ddl Enterococcus faecium, ddl Enterococcus faecalis, vanC1 and vanC2/C3 genes, and a high-resolution melting (HRM) analysis of the groESL gene for the differentiation of Enterococcus casseliflavus and Enterococcus gallinarum; (2) Bruker MS; (3) VITEK MS; and (4) the VITEK 2 system. 16S rRNA gene sequencing was used as a reference method in the study. The 132 isolates were identified as 32 E. faecalis, 63 E. faecium, 16 E. casseliflavus and 21 E. gallinarum. The multiplex PCR, Bruker MS and VITEK MS were able to identify all the isolates correctly at the species level. The VITEK 2 system could identify 131/132 (99.2 %) and 121/132 (91.7 %) of the isolates at the genus and species levels, respectively. The HRM-groESL assay identified all (21/21) E. gallinarum isolates and 81.3 % (13/16) of the E. casseliflavus isolates. The PCR methods described in the present study are effective in identifying the enterococcal species. MALDI-TOF MS is a rapid, reliable and cost-effective identification technique for enterococci. The VITEK 2 system is less efficient at detecting non-faecalis and non-faecium Enterococcus species.

Recommendations for Improving Identification and Quantification in Non-Targeted, GC-MS-Based Metabolomic Profiling of Human Plasma

PubMed Central

Wang, Hanghang; Muehlbauer, Michael J.; O’Neal, Sara K.; Newgard, Christopher B.; Hauser, Elizabeth R.; Shah, Svati H.

2017-01-01

The field of metabolomics as applied to human disease and health is rapidly expanding. In recent efforts of metabolomics research, greater emphasis has been placed on quality control and method validation. In this study, we report an experience with quality control and a practical application of method validation. Specifically, we sought to identify and modify steps in gas chromatography-mass spectrometry (GC-MS)-based, non-targeted metabolomic profiling of human plasma that could influence metabolite identification and quantification. Our experimental design included two studies: (1) a limiting-dilution study, which investigated the effects of dilution on analyte identification and quantification; and (2) a concentration-specific study, which compared the optimal plasma extract volume established in the first study with the volume used in the current institutional protocol. We confirmed that contaminants, concentration, repeatability and intermediate precision are major factors influencing metabolite identification and quantification. In addition, we established methods for improved metabolite identification and quantification, which were summarized to provide recommendations for experimental design of GC-MS-based non-targeted profiling of human plasma. PMID:28841195

2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification.

PubMed

Herner, András; Marjanovic, Jasmina; Lewandowski, Tracey M; Marin, Violeta; Patterson, Melanie; Miesbauer, Laura; Ready, Damien; Williams, Jon; Vasudevan, Anil; Lin, Qing

2016-11-09

Photoaffinity labels are powerful tools for dissecting ligand-protein interactions, and they have a broad utility in medicinal chemistry and drug discovery. Traditional photoaffinity labels work through nonspecific C-H/X-H bond insertion reactions with the protein of interest by the highly reactive photogenerated intermediate. Herein, we report a new photoaffinity label, 2-aryl-5-carboxytetrazole (ACT), that interacts with the target protein via a unique mechanism in which the photogenerated carboxynitrile imine reacts with a proximal nucleophile near the target active site. In two distinct case studies, we demonstrate that the attachment of ACT to a ligand does not significantly alter the binding affinity and specificity of the parent drug. Compared with diazirine and benzophenone, two commonly used photoaffinity labels, in two case studies ACT showed higher photo-cross-linking yields toward their protein targets in vitro based on mass spectrometry analysis. In the in situ target identification studies, ACT successfully captured the desired targets with an efficiency comparable to the diazirine. We expect that further development of this class of photoaffinity labels will lead to a broad range of applications across target identification, and validation and elucidation of the binding site in drug discovery.

2-Aryl-5-carboxytetrazole as a New Photoaffinity Label for Drug Target Identification

PubMed Central

2016-01-01

Photoaffinity labels are powerful tools for dissecting ligand–protein interactions, and they have a broad utility in medicinal chemistry and drug discovery. Traditional photoaffinity labels work through nonspecific C–H/X–H bond insertion reactions with the protein of interest by the highly reactive photogenerated intermediate. Herein, we report a new photoaffinity label, 2-aryl-5-carboxytetrazole (ACT), that interacts with the target protein via a unique mechanism in which the photogenerated carboxynitrile imine reacts with a proximal nucleophile near the target active site. In two distinct case studies, we demonstrate that the attachment of ACT to a ligand does not significantly alter the binding affinity and specificity of the parent drug. Compared with diazirine and benzophenone, two commonly used photoaffinity labels, in two case studies ACT showed higher photo-cross-linking yields toward their protein targets in vitro based on mass spectrometry analysis. In the in situ target identification studies, ACT successfully captured the desired targets with an efficiency comparable to the diazirine. We expect that further development of this class of photoaffinity labels will lead to a broad range of applications across target identification, and validation and elucidation of the binding site in drug discovery. PMID:27740749

System identification and sensorimotor determinants of flight maneuvers in an insect

NASA Astrophysics Data System (ADS)

Sponberg, Simon; Hall, Robert; Roth, Eatai

Locomotor maneuvers are inherently closed-loop processes. They are generally characterized by the integration of multiple sensory inputs and adaptation or learning over time. To probe sensorimotor processing we take a system identification approach treating the underlying physiological systems as dynamic processes and altering the feedback topology in experiment and analysis. As a model system, we use agile hawk moths (Manduca sexta), which feed from real and robotic flowers while hovering in mid air. Moths rely on vision and mechanosensation to track floral targets and can do so at exceptionally low luminance levels despite hovering being a mechanically unstable behavior that requires neural feedback to stabilize. By altering the sensory environment and placing mechanical and visual signals in conflict we show a surprisingly simple linear summation of visual and mechanosensation produces a generative prediction of behavior to novel stimuli. Tracking performance is also limited more by the mechanics of flight than the magnitude of the sensory cue. A feedback systems approach to locomotor control results in new insights into how behavior emerges from the interaction of nonlinear physiological systems.

Children's identification of faces from lineups: the effects of lineup presentation and instructions on accuracy.

PubMed

Beresford, Jayne; Blades, Mark

2006-09-01

The authors investigated whether the type of lineup and instructions given to children 6-7 or 9-10 years of age affected their identification accuracy. Children witnessed a man stealing property and were later asked to identify him in either photo or video lineups. Some lineups contained the target and some did not. Two lineup procedures were used (standard or elimination), and 2 types of instruction were used (standard or cautioning about false identification). Standard lineups with cautioning instructions decreased target-absent errors with no associated reduction in correct identifications, but elimination lineups did not. Lineup media had an interaction effect whereby correct identifications were reduced in video but not photo elimination lineups. The results are discussed in a forensic context. (c) 2006 APA, all rights reserved

Method To Identify Specific Inhibiutors Of Imp Dehydrogenase

DOEpatents

Collart, Frank R.; Huberman, Eliezer

2000-11-28

This invention relates to methods to identify specific inhibitors of the purine nucleotide synthesis enzyme, IMP dehydrogenase (IMPDH). IMPDH is an essential enzyme found in all free-living organisms from humans to bacteria and is an important therapeutic target. The invention allows the identification of specific inhibitors of any IMPDH enzyme which can be expressed in a functional form in a recombinant host cell. A variety of eukaryotic or prokaryotic host systems commonly used for the expression of recombinant proteins are suitable for the practice of the invention. The methods are amenable to high throughput systems for the screening of inhibitors generated by combinatorial chemistry or other methods such as antisense molecule production. Utilization of exogenous guanosine as a control component of the methods allows for the identification of inhibitors specific for IMPDH rather than other causes of decreased cell proliferation.

Driver landmark and traffic sign identification in early Alzheimer's disease.

PubMed

Uc, E Y; Rizzo, M; Anderson, S W; Shi, Q; Dawson, J D

2005-06-01

To assess visual search and recognition of roadside targets and safety errors during a landmark and traffic sign identification task in drivers with Alzheimer's disease. 33 drivers with probable Alzheimer's disease of mild severity and 137 neurologically normal older adults underwent a battery of visual and cognitive tests and were asked to report detection of specific landmarks and traffic signs along a segment of an experimental drive. The drivers with mild Alzheimer's disease identified significantly fewer landmarks and traffic signs and made more at-fault safety errors during the task than control subjects. Roadside target identification performance and safety errors were predicted by scores on standardised tests of visual and cognitive function. Drivers with Alzheimer's disease are impaired in a task of visual search and recognition of roadside targets; the demands of these targets on visual perception, attention, executive functions, and memory probably increase the cognitive load, worsening driving safety.

Recent Advance in Liquid Chromatography/Mass Spectrometry Techniques for Environmental Analysis in Japan

PubMed Central

Suzuki, Shigeru

2014-01-01

The techniques and measurement methods developed in the Environmental Survey and Monitoring of Chemicals by Japan’s Ministry of the Environment, as well as a large amount of knowledge archived in the survey, have led to the advancement of environmental analysis. Recently, technologies such as non-target liquid chromatography/high resolution mass spectrometry and liquid chromatography with micro bore column have further developed the field. Here, the general strategy of a method developed for the liquid chromatography/mass spectrometry (LC/MS) analysis of environmental chemicals with a brief description is presented. Also, a non-target analysis for the identification of environmental pollutants using a provisional fragment database and “MsMsFilter,” an elemental composition elucidation tool, is presented. This analytical method is shown to be highly effective in the identification of a model chemical, the pesticide Bendiocarb. Our improved micro-liquid chromatography injection system showed substantially enhanced sensitivity to perfluoroalkyl substances, with peak areas 32–71 times larger than those observed in conventional LC/MS. PMID:26819891

The current status of the MASHA setup

NASA Astrophysics Data System (ADS)

Vedeneev, V. Yu.; Rodin, A. M.; Krupa, L.; Belozerov, A. V.; Chernysheva, E. V.; Dmitriev, S. N.; Gulyaev, A. V.; Gulyaeva, A. V.; Kamas, D.; Kliman, J.; Komarov, A. B.; Motycak, S.; Novoselov, A. S.; Salamatin, V. S.; Stepantsov, S. V.; Podshibyakin, A. V.; Yukhimchuk, S. A.; Granja, C.; Pospisil, S.

2017-11-01

The MASHA setup designed as the mass-separator with the resolving power of about 1700, which allows mass identification of superheavy nuclides is described. The setup uses solid ISOL (Isotope Separation On-Line) method. In the present article the upgrade of some parts of MASHA are described: target box (rotating target + hot catcher), ion source based on electron cyclotron resonance, data acquisition, beam diagnostics and control systems. The upgrade is undertaken in order to increase the total separation efficiency, reduce the separation time, of the installation and working stability and make possible continuous measurements at high beam currents. Ion source efficiency was measured in autonomous regime with using calibrated gas leaks of Kr and Xe injected directly to ion source. Some results of the first experiments for production of radon isotopes using the multi-nucleon transfer reaction 48Ca+242Pu are described in the present article. The using of TIMEPIX detector with MASHA setup for neutron-rich Rn isotopes identification is also described.

United States Department of Agriculture-Agricultural Research Service: advances in the molecular genetic analysis of insects and their application to pest management.

PubMed

Handler, Alfred M; Beeman, Richard W

2003-01-01

USDA-ARS scientists have made important contributions to the molecular genetic analysis of agriculturally important insects, and have been in the forefront of using this information for the development of new pest management strategies. Advances have been made in the identification and analysis of genetic systems involved in insect development, reproduction and behavior which enable the identification of new targets for control, as well as the development of highly specific insecticidal products. Other studies have been on the leading edge of developing gene transfer technology to better elucidate these biological processes though functional genomics and to develop new transgenic strains for biological control. Important contributions have also been made to the development and use of molecular markers and methodologies to identify and track insect populations. The use of molecular genetic technology and strategies will become increasingly important to pest management as genomic sequencing information becomes available from important pest insects, their targets and other associated organisms.

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

PubMed Central

Joubert, Fourie; Harrison, Claudia M; Koegelenberg, Riaan J; Odendaal, Christiaan J; de Beer, Tjaart AP

2009-01-01

Background Up to half a billion human clinical cases of malaria are reported each year, resulting in about 2.7 million deaths, most of which occur in sub-Saharan Africa. Due to the over-and misuse of anti-malarials, widespread resistance to all the known drugs is increasing at an alarming rate. Rational methods to select new drug target proteins and lead compounds are urgently needed. The Discovery system provides data mining functionality on extensive annotations of five malaria species together with the human and mosquito hosts, enabling the selection of new targets based on multiple protein and ligand properties. Methods A web-based system was developed where researchers are able to mine information on malaria proteins and predicted ligands, as well as perform comparisons to the human and mosquito host characteristics. Protein features used include: domains, motifs, EC numbers, GO terms, orthologs, protein-protein interactions, protein-ligand interactions and host-pathogen interactions among others. Searching by chemical structure is also available. Results An in silico system for the selection of putative drug targets and lead compounds is presented, together with an example study on the bifunctional DHFR-TS from Plasmodium falciparum. Conclusion The Discovery system allows for the identification of putative drug targets and lead compounds in Plasmodium species based on the filtering of protein and chemical properties. PMID:19642978

SLATE: scanning laser automatic threat extraction

NASA Astrophysics Data System (ADS)

Clark, David J.; Prickett, Shaun L.; Napier, Ashley A.; Mellor, Matthew P.

2016-10-01

SLATE is an Autonomous Sensor Module (ASM) designed to work with the SAPIENT system providing accurate location tracking and classifications of targets that pass through its field of view. The concept behind the SLATE ASM is to produce a sensor module that provides a complementary view of the world to the camera-based systems that are usually used for wide area surveillance. Cameras provide a hi-fidelity, human understandable view of the world with which tracking and identification algorithms can be used. Unfortunately, positioning and tracking in a 3D environment is difficult to implement robustly, making location-based threat assessment challenging. SLATE uses a Scanning Laser Rangefinder (SLR) that provides precise (<1cm) positions, sizes, shapes and velocities of targets within its field-of-view (FoV). In this paper we will discuss the development of the SLATE ASM including the techniques used to track and classify detections that move through the field of view of the sensor providing the accurate tracking information to the SAPIENT system. SLATE's ability to locate targets precisely allows subtle boundary-crossing judgements, e.g. on which side of a chain-link fence a target is. SLATE's ability to track targets in 3D throughout its FoV enables behavior classification such as running and walking which can provide an indication of intent and help reduce false alarm rates.

Improving the identification accuracy of senior witnesses: do prelineup questions and sequential testing help?

PubMed

Memon, Amina; Gabbert, Fiona

2003-04-01

Eyewitness research has identified sequential lineup testing as a way of reducing false lineup choices while maintaining accurate identifications. The authors examined the usefulness of this procedure for reducing false choices in older adults. Young and senior witnesses viewed a crime video and were later presented with target present orabsent lineups in a simultaneous or sequential format. In addition, some participants received prelineup questions about their memory for a perpetrator's face and about their confidence in their ability to identify the culprit or to correctly reject the lineup. The sequential lineup reduced false choosing rates among young and older adults in target-absent conditions. In target-present conditions, sequential testing significantly reduced the correct identification rate in both age groups.

Utilizing random Forest QSAR models with optimized parameters for target identification and its application to target-fishing server.

PubMed

Lee, Kyoungyeul; Lee, Minho; Kim, Dongsup

2017-12-28

The identification of target molecules is important for understanding the mechanism of "target deconvolution" in phenotypic screening and "polypharmacology" of drugs. Because conventional methods of identifying targets require time and cost, in-silico target identification has been considered an alternative solution. One of the well-known in-silico methods of identifying targets involves structure activity relationships (SARs). SARs have advantages such as low computational cost and high feasibility; however, the data dependency in the SAR approach causes imbalance of active data and ambiguity of inactive data throughout targets. We developed a ligand-based virtual screening model comprising 1121 target SAR models built using a random forest algorithm. The performance of each target model was tested by employing the ROC curve and the mean score using an internal five-fold cross validation. Moreover, recall rates for top-k targets were calculated to assess the performance of target ranking. A benchmark model using an optimized sampling method and parameters was examined via external validation set. The result shows recall rates of 67.6% and 73.9% for top-11 (1% of the total targets) and top-33, respectively. We provide a website for users to search the top-k targets for query ligands available publicly at http://rfqsar.kaist.ac.kr . The target models that we built can be used for both predicting the activity of ligands toward each target and ranking candidate targets for a query ligand using a unified scoring scheme. The scores are additionally fitted to the probability so that users can estimate how likely a ligand-target interaction is active. The user interface of our web site is user friendly and intuitive, offering useful information and cross references.

Research on energy transmission calculation problem on laser detecting submarine

NASA Astrophysics Data System (ADS)

Fu, Qiang; Li, Yingchao; Zhang, Lizhong; Wang, Chao; An, Yan

2014-12-01

The laser detection and identification is based on the method of using laser as the source of signal to scan the surface of ocean. If the laser detection equipment finds out the target, it will immediately reflect the returning signal, and then through receiving and disposing the returning signal by the receiving system, to realize the function of detection and identification. Two mediums channels should be though in the process of laser detection transmission, which are the atmosphere and the seawater. The energy loss in the process of water transport, mainly considering the surface reflection and scattering attenuation and internal attenuation factors such as seawater. The energy consumption though atmospheric transmission, mainly considering the absorption of atmospheric and the attenuation causing by scattering, the energy consumption though seawater transmission, mainly considering the element such as surface reflection, the attenuation of scattering and internal attenuation of seawater. On the basis of the analysis and research, through the mode of establishment of atmospheric scattering, the model of sea surface reflection and the model of internal attenuation of seawater, determine the power dissipation of emitting lasers system, calculates the signal strength that reaches the receiver. Under certain conditions, the total attenuation of -98.92 dB by calculation, and put forward the related experiment scheme by the use of Atmospheric analog channel, seawater analog channel. In the experiment of the theory, we use the simulation pool of the atmosphere and the sea to replace the real environment where the laser detection system works in this kind of situation. To start with, we need to put the target in the simulating seawater pool of 10 meters large and then control the depth of the target in the sea level. We, putting the laser detection system in position where it is 2 kilometers far from one side, secondly use the equipment to aim at the target in some distance. Lastly, by launching and detecting the signal of returning wave, identify the effect of the image produced by the system.

Blueprint for antimicrobial hit discovery targeting metabolic networks.

PubMed

Shen, Y; Liu, J; Estiu, G; Isin, B; Ahn, Y-Y; Lee, D-S; Barabási, A-L; Kapatral, V; Wiest, O; Oltvai, Z N

2010-01-19

Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy.

Advances in the Engineering of the Gene Editing Enzymes and the Genomes: Understanding and Handling the Off-Target Effects of CRISPR/Cas9.

PubMed

Yin, Yufang; Wang, Qian; Xiao, Li; Wang, Fengjiao; Song, Zhuo; Zhou, Cuilan; Liu, Xuan; Xing, Chungen; He, Nongyue; Li, Kai; Feng, Yan; Zhang, Jia

2018-03-01

In the past decades, significant progresses have been achieved in genetic engineering of nucleases. Among the genetically engineered nucleases, zinc finger nucleases, transcription activator-like (TAL) effector nucleases, and CRIPSPR/Cas9 system form a new field of gene editing. The gene editing efficiency or targeting effect and the off-target effect are the two major determinant factors in evaluating the usefulness of a new enzyme. Engineering strategies in improving these gene editing enzymes, particularly in minimizing their off-target effects, are the focus of this paper. Examples of using these genetically engineered enzymes in genome modification are discussed in order to better understand the requirement of engineering efforts in obtaining more powerful and useful gene editing enzymes. In addition, the identification of naturally existed anti-Cas proteins has been employed in minimizing off-target effects. Considering the future application in human gene therapy, optimization of these well recognized gene editing enzymes and exploration of more novel enzymes are both required. Before people find an ideal gene editing system having virtually no off-target effect, technologies used to screen and identify off-target effects are of importance in clinical trials employing gene therapy.

The druggable genome and support for target identification and validation in drug development.

PubMed

Finan, Chris; Gaulton, Anna; Kruger, Felix A; Lumbers, R Thomas; Shah, Tina; Engmann, Jorgen; Galver, Luana; Kelley, Ryan; Karlsson, Anneli; Santos, Rita; Overington, John P; Hingorani, Aroon D; Casas, Juan P

2017-03-29

Target identification (determining the correct drug targets for a disease) and target validation (demonstrating an effect of target perturbation on disease biomarkers and disease end points) are important steps in drug development. Clinically relevant associations of variants in genes encoding drug targets model the effect of modifying the same targets pharmacologically. To delineate drug development (including repurposing) opportunities arising from this paradigm, we connected complex disease- and biomarker-associated loci from genome-wide association studies to an updated set of genes encoding druggable human proteins, to agents with bioactivity against these targets, and, where there were licensed drugs, to clinical indications. We used this set of genes to inform the design of a new genotyping array, which will enable association studies of druggable genes for drug target selection and validation in human disease. Copyright © 2017, American Association for the Advancement of Science.

A systems biology approach identified different regulatory networks targeted by KSHV miR-K12-11 in B cells and endothelial cells.

PubMed

Yang, Yajie; Boss, Isaac W; McIntyre, Lauren M; Renne, Rolf

2014-08-08

Kaposi's sarcoma associated herpes virus (KSHV) is associated with tumors of endothelial and lymphoid origin. During latent infection, KSHV expresses miR-K12-11, an ortholog of the human tumor gene hsa-miR-155. Both gene products are microRNAs (miRNAs), which are important post-transcriptional regulators that contribute to tissue specific gene expression. Advances in target identification technologies and molecular interaction databases have allowed a systems biology approach to unravel the gene regulatory networks (GRNs) triggered by miR-K12-11 in endothelial and lymphoid cells. Understanding the tissue specific function of miR-K12-11 will help to elucidate underlying mechanisms of KSHV pathogenesis. Ectopic expression of miR-K12-11 differentially affected gene expression in BJAB cells of lymphoid origin and TIVE cells of endothelial origin. Direct miRNA targeting accounted for a small fraction of the observed transcriptome changes: only 29 genes were identified as putative direct targets of miR-K12-11 in both cell types. However, a number of commonly affected biological pathways, such as carbohydrate metabolism and interferon response related signaling, were revealed by gene ontology analysis. Integration of transcriptome profiling, bioinformatic algorithms, and databases of protein-protein interactome from the ENCODE project identified different nodes of GRNs utilized by miR-K12-11 in a tissue-specific fashion. These effector genes, including cancer associated transcription factors and signaling proteins, amplified the regulatory potential of a single miRNA, from a small set of putative direct targets to a larger set of genes. This is the first comparative analysis of miRNA-K12-11's effects in endothelial and B cells, from tissues infected with KSHV in vivo. MiR-K12-11 was able to broadly modulate gene expression in both cell types. Using a systems biology approach, we inferred that miR-K12-11 establishes its GRN by both repressing master TFs and influencing signaling pathways, to counter the host anti-viral response and to promote proliferation and survival of infected cells. The targeted GRNs are more reproducible and informative than target gene identification, and our approach can be applied to other regulatory factors of interest.

Molecular targets of alcohol action: translational research for pharmacotherapy development and screening

PubMed Central

Gorini, Giorgio; Bell, Richard L.; Mayfield, R. Dayne

2016-01-01

Summary Alcohol abuse and dependence are multifaceted disorders with neurobiological, psychological, and environmental components. Research on other complex neuropsychiatric diseases suggests that genetically influenced intermediate characteristics affect the risk for heavy alcohol consumption and its consequences. Diverse therapeutic interventions can be developed through identification of reliable biomarkers for this disorder and new pharmacological targets for its treatment. Advances in the fields of genomics and proteomics offer a number of possible targets for the development of new therapeutic approaches. This brain-focused review highlights studies identifying neurobiological systems associated with these targets and possible pharmacotherapies, summarizing evidence from clinically relevant animal and human studies, as well as sketching improvements and challenges facing the fields of proteomics and genomics. Concluding thoughts on using results from these profiling technologies for medication development are also presented. PMID:21199775

Natural Products as a Source for Novel Antibiotics.

PubMed

Moloney, Mark G

2016-08-01

Natural products have historically been of crucial importance in the identification and development of antibacterial agents. Interest in these systems has waned in recent years, but the rapid emergence of resistant bacterial strains has forced their re-evaluation as a route to identify novel chemical skeletons with antibacterial activity for elaboration in drug development. This overview examines the current situation, highlights new natural product systems which have been found, together with re-examination of some old ones, and new technologies for their identification. While natural products certainly have the potential to re-emerge as a key start-point in antibacterial drug discovery, reports of new or reinvestigated structures need to be supported with sufficient quality chemical (solubility, stability), biochemical (including toxicity in particular, along with target information) and microbiological [minimum inhibitory concentration (MIC) and resistance frequency] validation data to assist in the identification of promising hit structures and to avoid wasted effort from trawling over already cultivated territory. This is particularly important in a resource-limited research environment. Copyright © 2016 Elsevier Ltd. All rights reserved.

Development of a Photo-Cross-Linkable Diaminoquinazoline Inhibitor for Target Identification in Plasmodium falciparum.

PubMed

Lubin, Alexandra S; Rueda-Zubiaurre, Ainoa; Matthews, Holly; Baumann, Hella; Fisher, Fabio R; Morales-Sanfrutos, Julia; Hadavizadeh, Kate S; Nardella, Flore; Tate, Edward W; Baum, Jake; Scherf, Artur; Fuchter, Matthew J

2018-04-13

Diaminoquinazolines represent a privileged scaffold for antimalarial discovery, including use as putative Plasmodium histone lysine methyltransferase inhibitors. Despite this, robust evidence for their molecular targets is lacking. Here we report the design and development of a small-molecule photo-cross-linkable probe to investigate the targets of our diaminoquinazoline series. We demonstrate the effectiveness of our designed probe for photoaffinity labeling of Plasmodium lysates and identify similarities between the target profiles of the probe and the representative diaminoquinazoline BIX-01294. Initial pull-down proteomics experiments identified 104 proteins from different classes, many of which are essential, highlighting the suitability of the developed probe as a valuable tool for target identification in Plasmodium falciparum.

PharmMapper server: a web server for potential drug target identification using pharmacophore mapping approach

PubMed Central

Liu, Xiaofeng; Ouyang, Sisheng; Yu, Biao; Liu, Yabo; Huang, Kai; Gong, Jiayu; Zheng, Siyuan; Li, Zhihua; Li, Honglin; Jiang, Hualiang

2010-01-01

In silico drug target identification, which includes many distinct algorithms for finding disease genes and proteins, is the first step in the drug discovery pipeline. When the 3D structures of the targets are available, the problem of target identification is usually converted to finding the best interaction mode between the potential target candidates and small molecule probes. Pharmacophore, which is the spatial arrangement of features essential for a molecule to interact with a specific target receptor, is an alternative method for achieving this goal apart from molecular docking method. PharmMapper server is a freely accessed web server designed to identify potential target candidates for the given small molecules (drugs, natural products or other newly discovered compounds with unidentified binding targets) using pharmacophore mapping approach. PharmMapper hosts a large, in-house repertoire of pharmacophore database (namely PharmTargetDB) annotated from all the targets information in TargetBank, BindingDB, DrugBank and potential drug target database, including over 7000 receptor-based pharmacophore models (covering over 1500 drug targets information). PharmMapper automatically finds the best mapping poses of the query molecule against all the pharmacophore models in PharmTargetDB and lists the top N best-fitted hits with appropriate target annotations, as well as respective molecule’s aligned poses are presented. Benefited from the highly efficient and robust triangle hashing mapping method, PharmMapper bears high throughput ability and only costs 1 h averagely to screen the whole PharmTargetDB. The protocol was successful in finding the proper targets among the top 300 pharmacophore candidates in the retrospective benchmarking test of tamoxifen. PharmMapper is available at http://59.78.96.61/pharmmapper. PMID:20430828

Correlation Based Target Location and Identification

DTIC Science & Technology

1992-12-01

Research Daugman (7) cites research on the mammalian visual nervous system (retina, lateral geniculate , and primary visual cortex) as motivation for...brains, they can still sort slides into natural categories such as people, trees, and bodies of water, a capability that humans do easily. As such...critical neurobiological variables of a given neuron’s orientation and spatial frequency preference, the tuning bandwidths for these variables, the

Comprehensive analytical strategy for biomonitoring of pesticides in urine by liquid chromatography–orbitrap high resolution masss pectrometry.

PubMed

Roca, M; Leon, N; Pastor, A; Yusà, V

2014-12-29

In this study we propose an analytical strategy that combines a target approach for the quantitative analysis of contemporary pesticide metabolites with a comprehensive post-target screening for the identification of biomarkers of exposure to environmental contaminants in urine using liquid chromatography coupled to high-resolution mass spectrometry (LC–HRMS). The quantitative method for the target analysis of 29 urinary metabolites of organophosphate (OP) insecticides, synthetic pyrethroids, herbicides and fungicides was validated after a previous statistical optimization of the main factors governing the ion source ionization and a fragmentation study using the high energy collision dissociation (HCD) cell. The full scan accurate mass data were acquired with a resolving power of 50,000 FWHM (scan speed, 2 Hz), in both ESI+ and ESI− modes, and with and without HCD-fragmentation. The method – LOQ was lower than 3.2 μg L−1 for the majority of the analytes. For post-target screening a customized theoretical database was built, for the identification of 60 metabolites including pesticides, PAHs, phenols, and other metabolites of environmental pollutants. For identification purposes, accurate exact mass with less than 5 ppm, and diagnostic ions including isotopes and/or fragments were used. The analytical strategy was applied to 20 urine sample collected from children living in Valencia Region. Eleven target metabolites were detected with concentrations ranging from 1.18 to 131 μg L−1. Likewise, several compounds were tentatively identified in the post-target analysis belonging to the families of phthalates, phenols and parabenes. The proposed strategy is suitable for the determination of target pesticide biomarkers in urine in the framework of biomonitoring studies, and appropriate for the identification of other non-target metabolites.

Interleukin 1 Receptor Antagonist Deficiency Presenting as Infantile Pustulosis Mimicking Infantile Pustular Psoriasis

PubMed Central

Minkis, Kira; Aksentijevich, Ivona; Goldbach-Mansky, Raphaela; Magro, Cynthia; Scott, Rachelle; Davis, Jessica G.; Sardana, Niti; Herzog, Ronit

2012-01-01

Background Deficiency of interleukin 1 receptor antagonist (DIRA) is a recently described autoinflammatory syndrome of skin and bone caused by recessive mutations in the gene encoding the interleukin 1 receptor antagonist. Few studies have been published about this debilitating condition. Early identification is critical for targeted lifesaving intervention. Observations A male infant, born to nonconsanguineous Puerto Rican parents, was referred for management of a pustular eruption diagnosed as pustular psoriasis. At 2 months of age, the infant developed a pustular eruption. After extensive evaluation, he was confirmed to be homozygous for a 175-kb genomic deletion on chromosome 2 that includes the IL1RN gene, commonly found in Puerto Ricans. Therapy with anakinra was initiated, with rapid clearance of skin lesions and resolution of systemic inflammation. Conclusions Recent identification of DIRA as a disease entity, compounded by the limited number of reported cases, makes early identification difficult. It is critical to consider this entity in the differential diagnosis of infantile pustulosis. Targeted therapy with the recombinant human interleukin 1 receptor antagonist anakinra can be lifesaving if initiated early. A high carrier frequency of the 175-kb DIRA-associated genomic deletion in the Puerto Rican population strongly supports testing infants presenting with unexplained pustulosis in patients from this geographic region. PMID:22431714

Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method.

PubMed

Riera-Borrull, Marta; Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Luciano, Fedra; Ras, Rosa; Cuyàs, Elisabet; Camps, Jordi; Segura-Carretero, Antonio; Menendez, Javier A; Joven, Jorge; Fernández-Arroyo, Salvador

2016-01-01

Abnormalities in mitochondrial metabolism and regulation of energy balance contribute to human diseases. The consequences of high fat and other nutrient intake, and the resulting acquired mitochondrial dysfunction, are essential to fully understand common disorders, including obesity, cancer, and atherosclerosis. To simultaneously and noninvasively measure and quantify indirect markers of mitochondrial function, we have developed a method based on gas chromatography coupled to quadrupole-time of flight mass spectrometry and an electron ionization interface, and validated the system using plasma from patients with peripheral artery disease, human cancer cells, and mouse tissues. This approach was used to increase sensibility in the measurement of a wide dynamic range and chemical diversity of multiple intermediate metabolites used in energy metabolism. We demonstrate that our targeted metabolomics method allows for quick and accurate identification and quantification of molecules, including the measurement of small yet significant biological changes in experimental samples. The apparently low process variability required for its performance in plasma, cell lysates, and tissues allowed a rapid identification of correlations between interconnected pathways. Our results suggest that delineating the process of energy generation by targeted metabolomics can be a valid surrogate for predicting mitochondrial dysfunction in biological samples. Importantly, when used in plasma, targeted metabolomics should be viewed as a robust and noninvasive source of biomarkers in specific pathophysiological scenarios.

Exploring the Process of Energy Generation in Pathophysiology by Targeted Metabolomics: Performance of a Simple and Quantitative Method

NASA Astrophysics Data System (ADS)

Riera-Borrull, Marta; Rodríguez-Gallego, Esther; Hernández-Aguilera, Anna; Luciano, Fedra; Ras, Rosa; Cuyàs, Elisabet; Camps, Jordi; Segura-Carretero, Antonio; Menendez, Javier A.; Joven, Jorge; Fernández-Arroyo, Salvador

2016-01-01

Abnormalities in mitochondrial metabolism and regulation of energy balance contribute to human diseases. The consequences of high fat and other nutrient intake, and the resulting acquired mitochondrial dysfunction, are essential to fully understand common disorders, including obesity, cancer, and atherosclerosis. To simultaneously and noninvasively measure and quantify indirect markers of mitochondrial function, we have developed a method based on gas chromatography coupled to quadrupole-time of flight mass spectrometry and an electron ionization interface, and validated the system using plasma from patients with peripheral artery disease, human cancer cells, and mouse tissues. This approach was used to increase sensibility in the measurement of a wide dynamic range and chemical diversity of multiple intermediate metabolites used in energy metabolism. We demonstrate that our targeted metabolomics method allows for quick and accurate identification and quantification of molecules, including the measurement of small yet significant biological changes in experimental samples. The apparently low process variability required for its performance in plasma, cell lysates, and tissues allowed a rapid identification of correlations between interconnected pathways. Our results suggest that delineating the process of energy generation by targeted metabolomics can be a valid surrogate for predicting mitochondrial dysfunction in biological samples. Importantly, when used in plasma, targeted metabolomics should be viewed as a robust and noninvasive source of biomarkers in specific pathophysiological scenarios.

2-D Difference in gel electrophoresis combined with Pro-Q Diamond staining: a successful approach for the identification of kinase/phosphatase targets.

PubMed

Orsatti, Laura; Forte, Eleonora; Tomei, Licia; Caterino, Marianna; Pessi, Antonello; Talamo, Fabio

2009-07-01

The protein tyrosine phosphatase PRL-3 is an appealing therapeutic cancer target for its well described involvement in the metastasis progression. Nevertheless, very little is known about PRL-3 role in tumorigenesis. In the attempt to identify the protein target of this phosphatase we have devised a model system based on the use of highly invasive HCT116 colon cancer cells over-expressing PRL-3. We used 2-D difference gel electrophoresis combined with the fluorescence staining Pro-Q Diamond selective for phosphorylated proteins to monitor changes in the phosphorylation status of possible substrates. Proteins whose phosphorylation level was negatively affected by PRL-3 over-expression were identified by MS. Two proteins were found to be significantly dephosphorylated in this condition, the cytoskeletal protein ezrin and elongation factor 2. Ezrin has already been described as having a proactive role in cancer metastasis through control of its phosphorylation status, and the PRL-3-induced modulation of ezrin phosphorylation in HCT116 and human umblical vascular endothelial cells is the subject of a separate paper by Forte et al. [Biochim. Biophys. Acta 2008, 1783, 334-344]. The combination of 2-D difference in gel electrophoresis and Pro-Q Diamond was hence confirmed successful in analyzing changes of protein phosphorylation which enable the identification of kinase/phosphatase targets.

Developments for Personalized Medicine of Lung Cancer Subtypes: Mass Spectrometry-Based Clinical Proteogenomic Analysis of Oncogenic Mutations.

PubMed

Nishimura, Toshihide; Nakamura, Haruhiko

2016-01-01

Molecular therapies targeting lung cancers with mutated epidermal growth factor receptor (EGFR) by EGFR-tyrosin kinase inhibitors (EGFR-TKIs), gefitinib and erlotinib, changed the treatment system of lung cancer. It was revealed that drug efficacy differs by race (e.g., Caucasians vs. Asians) due to oncogenic driver mutations specific to each race, exemplified by gefitinib / erlotinib. The molecular target drugs for lung cancer with anaplastic lymphoma kinase (ALK) gene translocation (the fusion gene, EML4-ALK) was approved, and those targeting lung cancers addicted ROS1, RET, and HER2 have been under development. Both identification and quantification of gatekeeper mutations need to be performed using lung cancer tissue specimens obtained from patients to improve the treatment for lung cancer patients: (1) identification and quantitation data of targeted mutated proteins, including investigation of mutation heterogeneity within a tissue; (2) exploratory mass spectrometry (MS)-based clinical proteogenomic analysis of mutated proteins; and also importantly (3) analysis of dynamic protein-protein interaction (PPI) networks of proteins significantly related to a subgroup of patients with lung cancer not only with good efficacy but also with acquired resistance. MS-based proteogenomics is a promising approach to directly capture mutated and fusion proteins expressed in a clinical sample. Technological developments are further expected, which will provide a powerful solution for the stratification of patients and drug discovery (Precision Medicine).

Common pitfalls in preclinical cancer target validation.

PubMed

Kaelin, William G

2017-07-01

An alarming number of papers from laboratories nominating new cancer drug targets contain findings that cannot be reproduced by others or are simply not robust enough to justify drug discovery efforts. This problem probably has many causes, including an underappreciation of the danger of being misled by off-target effects when using pharmacological or genetic perturbants in complex biological assays. This danger is particularly acute when, as is often the case in cancer pharmacology, the biological phenotype being measured is a 'down' readout (such as decreased proliferation, decreased viability or decreased tumour growth) that could simply reflect a nonspecific loss of cellular fitness. These problems are compounded by multiple hypothesis testing, such as when candidate targets emerge from high-throughput screens that interrogate multiple targets in parallel, and by a publication and promotion system that preferentially rewards positive findings. In this Perspective, I outline some of the common pitfalls in preclinical cancer target identification and some potential approaches to mitigate them.

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

NASA Astrophysics Data System (ADS)

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

2017-07-01

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

PHASTpep: Analysis Software for Discovery of Cell-Selective Peptides via Phage Display and Next-Generation Sequencing

PubMed Central

Dasa, Siva Sai Krishna; Kelly, Kimberly A.

2016-01-01

Next-generation sequencing has enhanced the phage display process, allowing for the quantification of millions of sequences resulting from the biopanning process. In response, many valuable analysis programs focused on specificity and finding targeted motifs or consensus sequences were developed. For targeted drug delivery and molecular imaging, it is also necessary to find peptides that are selective—targeting only the cell type or tissue of interest. We present a new analysis strategy and accompanying software, PHage Analysis for Selective Targeted PEPtides (PHASTpep), which identifies highly specific and selective peptides. Using this process, we discovered and validated, both in vitro and in vivo in mice, two sequences (HTTIPKV and APPIMSV) targeted to pancreatic cancer-associated fibroblasts that escaped identification using previously existing software. Our selectivity analysis makes it possible to discover peptides that target a specific cell type and avoid other cell types, enhancing clinical translatability by circumventing complications with systemic use. PMID:27186887

Synthesis of a beta-estradiol-biotin chimera that potently heterodimerizes estrogen receptor and streptavidin proteins in a yeast three-hybrid system.

PubMed

Hussey, Stephen L; Muddana, Smita S; Peterson, Blake R

2003-04-02

Small molecules that dimerize proteins in living cells provide powerful probes of biological processes and have potential as tools for the identification of protein targets of natural products. We synthesized 7-alpha-substituted derivatives of beta-estradiol tethered to the natural product biotin to regulate heterodimerization of estrogen receptor (ER) and streptavidin (SA) proteins expressed as components of a yeast three-hybrid system. Addition of an estradiol-biotin chimera bearing a 19-atom linker to yeast expressing DNA-bound ER-alpha or ER-beta LexA fusion proteins and wild-type SA protein fused to the B42 activation domain activated reporter gene expression by as much as 450-fold in vivo (10 muM ligand). Comparative analysis of lower affinity Y43A (biotin Kd approximately 100 pM) and W120A (biotin Kd approximately 100 nM) mutants of SA indicated that moderate affinity interactions can be readily detected with this system. Comparison of a 7-alpha-substituted estradiol-biotin chimera with a structurally similar dexamethasone-biotin chimera revealed that yeast expressing ER proteins can detect cognate ligands with up to 5-fold greater potency and 70-fold higher activity than yeast expressing analogous glucocorticoid receptor (GR) proteins. This approach may facilitate the identification of protein targets of biologically active small molecules screened against genetically encoded libraries of proteins expressed in yeast three-hybrid systems.

Systemic inflammatory response syndrome (SIRS)

PubMed Central

Balk, Robert A

2014-01-01

The concept of a systemic inflammatory response syndrome (SIRS) to describe the complex pathophysiologic response to an insult such as infection, trauma, burns, pancreatitis, or a variety of other injuries came from a 1991 consensus conference charged with the task of developing an easy-to-apply set of clinical parameters to aid in the early identification of potential candidates to enter into clinical trials to evaluate new treatments for sepsis. There was recognition that a diverse group of injuries produced a common inflammatory response in the host and provided attractive targets for new anti-inflammatory molecules designed to prevent further propagation and/or provide specific treatment. Effective application of these new anti-inflammatory strategies necessitated identification of early clinical markers that could be assessed in real-time and were likely to define a population of patients that would have a beneficial response to the targeted intervention. It was felt that early clinical manifestations might be more readily available to clinicians than more sophisticated and specific assays for inflammatory substances that were systemically released by the network of injurious inflammatory events. Therefore, the early definition of a systemic inflammatory response syndrome (SIRS) was built upon a foundation of basic clinical and laboratory abnormalities that were readily available in almost all clinical settings. With further refinement, it was hoped, that this definition would have a high degree of sensitivity, coupled with a reasonable degree of specificity. This manuscript reviews the derivation, application, utilization, potential benefits, and speculation regarding the future of the SIRS definition. PMID:24280933

A multisensor system for airborne surveillance of oil pollution

NASA Technical Reports Server (NTRS)

Edgerton, A. T.; Ketchal, R.; Catoe, C.

1973-01-01

The U.S. Coast Guard is developing a prototype airborne oil surveillance system for use in its Marine Environmental Protection Program. The prototype system utilizes an X-band side-looking radar, a 37-GHz imaging microwave radiometer, a multichannel line scanner, and a multispectral low light level system. The system is geared to detecting and mapping oil spills and potential pollution violators anywhere within a 25 nmi range of the aircraft flight track under all but extreme weather conditions. The system provides for false target discrimination and maximum identification of spilled materials. The system also provides an automated detection alarm, as well as a color display to achieve maximum coupling between the sensor data and the equipment operator.

Detection of High Energy Cosmic Rays with Advanced Thin Ionization Calorimeter, ATIC

NASA Technical Reports Server (NTRS)

Adams, J. H.; Ahn, E. J.; Ahn, H. S.; Bashindzhagyan, G.; Case, G.; Chang, J.; Christl, M.; Ellison, S.; Fazely, A. R.; Ganel, O.

2002-01-01

The author presents preliminary results of the first flight of the Advanced Thin Ionization Calorimeter (ATIC). ATIC is a multiple, long duration balloon flight, investigation for the study of cosmic ray spectra from below 50 GeV to near 100 TeV total energy, using a fully active Bismuth Germanate (BGO) calorimeter. It is equipped with the first large area mosaic of small fully depleted silicon detector pads capable of charge identification of cosmic rays from H to Fe. As a redundancy check for the charge identification and a coarse particle tracking system, three projective layers of x-y scintillator hodoscopes were employed, above, in the center and below a Carbon interaction 'target'.

Design of large zoom for visible and infrared optical system in hemisphere space

NASA Astrophysics Data System (ADS)

Xing, Yang-guang; Li, Lin; Zhang, Juan

2018-01-01

In the field of space optical, the application of advanced optical instruments for related target detection and identification has become an advanced technology in modern optics. In order to complete the task of search in wide field of view and detailed investigation in small field of view, it is inevitable to use the structure of the zoom system to achieve a better observation for important targets. The innovation of this paper lies in using the zoom optical system in space detection, which achieve firstly military needs of searched target in the large field of view and recognized target in the small field of view. At the same time, this paper also completes firstly the design of variable focus optical detection system in the range of hemisphere space, the zoom optical system is working in the range of visible and infrared wavelengths, the perspective angle reaches 360 ° and the zoom ratio of the visible system is up to 15. The visible system has a zoom range of 60-900 mm, a detection band of 0.48-0.70μm, and a F-number of 2.0 to 5.0. The infrared system has a zoom range of 150 900mm, a detection band of 8-12μm, and a F-number of 1.2 to 3.0. The MTF of the visible zoom system is above 0.4 at spatial frequency of 45 lp / mm, and the infrared zoom system is above 0.4 at spatial frequency of 11 lp / mm. The design results show that the system has a good image quality.

Characterization of Aspergillus species on Brazil nut from the Brazilian Amazonian region and development of a PCR assay for identification at the genus level

PubMed Central

2014-01-01

Background Brazil nut is a protein-rich extractivist tree crop in the Amazon region. Fungal contamination of shells and kernel material frequently includes the presence of aflatoxigenic Aspergillus species from the section Flavi. Aflatoxins are polyketide secondary metabolites, which are hepatotoxic carcinogens in mammals. The objectives of this study were to identify Aspergillus species occurring on Brazil nut grown in different states in the Brazilian Amazon region and develop a specific PCR method for collective identification of member species of the genus Aspergillus. Results Polyphasic identification of 137 Aspergillus strains isolated from Brazil nut shell material from cooperatives across the Brazilian Amazon states of Acre, Amapá and Amazonas revealed five species, with Aspergillus section Flavi species A. nomius and A. flavus the most abundant. PCR primers ASP_GEN_MTSSU_F1 and ASP_GEN_MTSSU_R1 were designed for the genus Aspergillus, targeting a portion of the mitochondrial small subunit ribosomal RNA gene. Primer specificity was validated through both electronic PCR against target gene sequences at Genbank and in PCR reactions against DNA from Aspergillus species and other fungal genera common on Brazil nut. Collective differentiation of the observed section Flavi species A. flavus, A. nomius and A. tamarii from other Aspergillus species was possible on the basis of RFLP polymorphism. Conclusions Given the abundance of Aspergillus section Flavi species A. nomius and A. flavus observed on Brazil nut, and associated risk of mycotoxin accumulation, simple identification methods for such mycotoxigenic species are of importance for Hazard Analysis Critical Control Point system implementation. The assay for the genus Aspergillus represents progress towards specific PCR identification and detection of mycotoxigenic species. PMID:24885088

Identification of Forensically Important Calliphoridae and Sarcophagidae Species Collected in Korea Using SNaPshot Multiplex System Targeting the Cytochrome c Oxidase Subunit I Gene

PubMed Central

Park, Ji Hye

2018-01-01

Estimation of postmortem interval (PMI) is paramount in modern forensic investigation. After the disappearance of the early postmortem phenomena conventionally used to estimate PMI, entomologic evidence provides important indicators for PMI estimation. The age of the oldest fly larvae or pupae can be estimated to pinpoint the time of oviposition, which is considered the minimum PMI (PMImin). The development rate of insects is usually temperature dependent and species specific. Therefore, species identification is mandatory for PMImin estimation using entomological evidence. The classical morphological identification method cannot be applied when specimens are damaged or have not yet matured. To overcome this limitation, some investigators employ molecular identification using mitochondrial cytochrome c oxidase subunit I (COI) nucleotide sequences. The molecular identification method commonly uses Sanger's nucleotide sequencing and molecular phylogeny, which are complex and time consuming and constitute another obstacle for forensic investigators. In this study, instead of using conventional Sanger's nucleotide sequencing, single-nucleotide polymorphisms (SNPs) in the COI gene region, which are unique between fly species, were selected and targeted for single-base extension (SBE) technology. These SNPs were genotyped using a SNaPshot® kit. Eleven Calliphoridae and seven Sarcophagidae species were covered. To validate this genotyping, fly DNA samples (103 adults, 84 larvae, and 4 pupae) previously confirmed by DNA barcoding were used. This method worked quickly with minimal DNA, providing a potential alternative to conventional DNA barcoding. Consisting of only a few simple electropherogram peaks, the results were more straightforward compared with those of the conventional DNA barcoding produced by Sanger's nucleotide sequencing. PMID:29682531

Study of environmental sound source identification based on hidden Markov model for robust speech recognition

NASA Astrophysics Data System (ADS)

Nishiura, Takanobu; Nakamura, Satoshi

2003-10-01

Humans communicate with each other through speech by focusing on the target speech among environmental sounds in real acoustic environments. We can easily identify the target sound from other environmental sounds. For hands-free speech recognition, the identification of the target speech from environmental sounds is imperative. This mechanism may also be important for a self-moving robot to sense the acoustic environments and communicate with humans. Therefore, this paper first proposes hidden Markov model (HMM)-based environmental sound source identification. Environmental sounds are modeled by three states of HMMs and evaluated using 92 kinds of environmental sounds. The identification accuracy was 95.4%. This paper also proposes a new HMM composition method that composes speech HMMs and an HMM of categorized environmental sounds for robust environmental sound-added speech recognition. As a result of the evaluation experiments, we confirmed that the proposed HMM composition outperforms the conventional HMM composition with speech HMMs and a noise (environmental sound) HMM trained using noise periods prior to the target speech in a captured signal. [Work supported by Ministry of Public Management, Home Affairs, Posts and Telecommunications of Japan.

Camouflage, detection and identification of moving targets

PubMed Central

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

Camouflage, detection and identification of moving targets.

PubMed

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

2013-05-07

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

Prioritizing and modelling of putative drug target proteins of Candida albicans by systems biology approach.

PubMed

Ismail, Tariq; Fatima, Nighat; Muhammad, Syed Aun; Zaidi, Syed Saoud; Rehman, Nisar; Hussain, Izhar; Tariq, Najam Us Sahr; Amirzada, Imran; Mannan, Abdul

2018-01-01

Candida albicans (Candida albicans) is one of the major sources of nosocomial infections in humans which may prove fatal in 30% of cases. The hospital acquired infection is very difficult to treat affectively due to the presence of drug resistant pathogenic strains, therefore there is a need to find alternative drug targets to cure this infection. In silico and computational level frame work was used to prioritize and establish antifungal drug targets of Candida albicans. The identification of putative drug targets was based on acquiring 5090 completely annotated genes of Candida albicans from available databases which were categorized into essential and non-essential genes. The result indicated that 9% of proteins were essential and could become potential candidates for intervention which might result in pathogen eradication. We studied cluster of orthologs and the subtractive genomic analysis of these essential proteins against human genome was made as a reference to minimize the side effects. It was seen that 14% of Candida albicans proteins were evolutionary related to the human proteins while 86% are non-human homologs. In the next step of compatible drug target selections, the non-human homologs were sequentially compared to the human microbiome data to minimize the potential effects against gut flora which accumulated to 38% of the essential genome. The sub-cellular localization of these candidate proteins in fungal cellular systems indicated that 80% of them are cytoplasmic, 10% are mitochondrial and the remaining 10% are associated with the cell wall. The role of these non-human and non-gut flora putative target proteins in Candida albicans biological pathways was studied. Due to their integrated and critical role in Candida albicans replication cycle, four proteins were selected for molecular modeling. For drug designing and development, four high quality and reliable protein models with more than 70% sequence identity were constructed. These proteins are used for the docking studies of the known and new ligands (unpublished data). Our study will be an effective framework for drug target identifications of pathogenic microbial strains and development of new therapies against the infections they cause.

Murine Models of Systemic Lupus Erythematosus

PubMed Central

Perry, Daniel; Sang, Allison; Yin, Yiming; Zheng, Ying-Yi; Morel, Laurence

2011-01-01

Systemic lupus erythematosus (SLE) is a multifactorial autoimmune disorder. The study of diverse mouse models of lupus has provided clues to the etiology of SLE. Spontaneous mouse models of lupus have led to identification of numerous susceptibility loci from which several candidate genes have emerged. Meanwhile, induced models of lupus have provided insight into the role of environmental factors in lupus pathogenesis as well as provided a better understanding of cellular mechanisms involved in the onset and progression of disease. The SLE-like phenotypes present in these models have also served to screen numerous potential SLE therapies. Due to the complex nature of SLE, it is necessary to understand the effect specific targeted therapies have on immune homeostasis. Furthermore, knowledge gained from mouse models will provide novel therapy targets for the treatment of SLE. PMID:21403825

Quantifying oncogenic phosphotyrosine signaling networks through systems biology.

PubMed

Del Rosario, Amanda M; White, Forest M

2010-02-01

Pathways linking oncogenic mutations to increased proliferative or migratory capacity are poorly characterized, yet provide potential targets for therapeutic intervention. As tyrosine phosphorylation signaling networks are known to mediate proliferation and migration, and frequently go awry in cancers, a comprehensive understanding of these networks in normal and diseased states is warranted. To this end, recent advances in mass spectrometry, protein microarrays, and computational algorithms provide insight into various aspects of the network including phosphotyrosine identification, analysis of kinase/phosphatase substrates, and phosphorylation-mediated protein-protein interactions. Here we detail technological advances underlying these system-level approaches and give examples of their applications. By combining multiple approaches, it is now possible to quantify changes in the phosphotyrosine signaling network with various oncogenic mutations, thereby unveiling novel therapeutic targets. Copyright 2009 Elsevier Ltd. All rights reserved.

Emerging therapeutic targets for treatment of leishmaniasis.

PubMed

Sundar, Shyam; Singh, Bhawana

2018-06-01

Parasitic diseases that pose a threat to human life include leishmaniasis - caused by protozoan parasite Leishmania species. Existing drugs have limitations due to deleterious side effects like teratogenicity, high cost and drug resistance. This calls for the need to have an insight into therapeutic aspects of disease. Areas covered: We have identified different drug targets via. molecular, imuunological, metabolic as well as by system biology approaches. We bring these promising drug targets into light so that they can be explored to their maximum. In an effort to bridge the gaps between existing knowledge and prospects of drug discovery, we have compiled interesting studies on drug targets, thereby paving the way for establishment of better therapeutic aspects. Expert opinion: Advancements in technology shed light on many unexplored pathways. Further probing of well established pathways led to the discovery of new drug targets. This review is a comprehensive report on current and emerging drug targets, with emphasis on several metabolic targets, organellar biochemistry, salvage pathways, epigenetics, kinome and more. Identification of new targets can contribute significantly towards strengthening the pipeline for disease elimination.

Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization

PubMed Central

Xu, Tao; Johnson, Cole A; Gestwicki, Jason E; Kumar, Anuj

2016-01-01

We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. one chimera consists of a FK506-binding protein (FKBp12) fused to a cellular ‘address’ (nuclear localization signal or nuclear export sequence). the second chimera consists of a target protein fused to a fluorescent protein and the FKBp12-rapamycin-binding (FrB) domain from FKBp-12-rapamycin associated protein 1 (Frap1, also known as mtor). rapamycin induces dimerization of the FKBp12- and FrB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss-of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment. PMID:21030958

Conditionally controlling nuclear trafficking in yeast by chemical-induced protein dimerization.

PubMed

Xu, Tao; Johnson, Cole A; Gestwicki, Jason E; Kumar, Anuj

2010-11-01

We present here a protocol to conditionally control the nuclear trafficking of target proteins in yeast. In this system, rapamycin is used to heterodimerize two chimeric proteins. One chimera consists of a FK506-binding protein (FKBP12) fused to a cellular 'address' (nuclear localization signal or nuclear export sequence). The second chimera consists of a target protein fused to a fluorescent protein and the FKBP12-rapamycin-binding (FRB) domain from FKBP-12-rapamycin associated protein 1 (FRAP1, also known as mTor). Rapamycin induces dimerization of the FKBP12- and FRB-containing chimeras; these interactions selectively place the target protein under control of the cell address, thereby directing the protein into or out of the nucleus. By chemical-induced dimerization, protein mislocalization is reversible and enables the identification of conditional loss-of-function and gain-of-function phenotypes, in contrast to other systems that require permanent modification of the targeted protein. Yeast strains for this analysis can be constructed in 1 week, and the technique allows protein mislocalization within 15 min after drug treatment.

Multi-centre evaluation of mass spectrometric identification of anaerobic bacteria using the VITEK® MS system.

PubMed

Garner, O; Mochon, A; Branda, J; Burnham, C-A; Bythrow, M; Ferraro, M; Ginocchio, C; Jennemann, R; Manji, R; Procop, G W; Richter, S; Rychert, J; Sercia, L; Westblade, L; Lewinski, M

2014-04-01

Accurate and timely identification of anaerobic bacteria is critical to successful treatment. Classic phenotypic methods for identification require long turnaround times and can exhibit poor species level identification. Matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) is an identification method that can provide rapid identification of anaerobes. We present a multi-centre study assessing the clinical performance of the VITEK(®) MS in the identification of anaerobic bacteria. Five different test sites analysed a collection of 651 unique anaerobic isolates comprising 11 different genera. Multiple species were included for several of the genera. Briefly, anaerobic isolates were applied directly to a well of a target plate. Matrix solution (α-cyano-4-hydroxycinnamic acid) was added and allowed to dry. Mass spectra results were generated with the VITEK(®) MS, and the comparative spectral analysis and organism identification were determined using the VITEK(®) MS database 2.0. Results were confirmed by 16S rRNA gene sequencing. Of the 651 isolates analysed, 91.2% (594/651) exhibited the correct species identification. An additional eight isolates were correctly identified to genus level, raising the rate of identification to 92.5%. Genus-level identification consisted of Actinomyces, Bacteroides and Prevotella species. Fusobacterium nucleatum, Actinomyces neuii and Bacteroides uniformis were notable for an increased percentage of no-identification results compared with the other anaerobes tested. VITEK(®) MS identification of clinically relevant anaerobes is highly accurate and represents a dramatic improvement over other phenotypic methods in accuracy and turnaround time. © 2013 The Authors Clinical Microbiology and Infection © 2013 European Society of Clinical Microbiology and Infectious Diseases.

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

DOE Office of Scientific and Technical Information (OSTI.GOV)

Wang, Xiangbo; Zhang, Lu; Ding, Nianhua

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 possessmore » 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.« less

Proteomic identification of aldolase A as an autoantibody target in patients with atypical movement disorders.

PubMed

Privitera, Daniela; Corti, Valeria; Alessio, Massimo; Volontè, Maria Antonietta; Volontè, Antonietta; Lampasona, Vito; Comi, Giancarlo; Martino, Gianvito; Franciotta, Diego; Furlan, Roberto; Fazio, Raffaella

2013-03-01

We tried to identify the target/s of autoantibodies to basal ganglia neurons found in a patient with hyperkinetic movement disorders (HMD) characterized by rapid, rhythmic involuntary movements or spasms in both face and neck. Patient and control sera were used in Western blot to probe mouse brain homogenates. Two-dimensional gel electrophoresis (2-DE) SDS-PAGE protein spots recognized by the patient's antibodies were excised and sequenced by mass spectrometry analysis, and the glycolytic enzyme aldolase A was identified as the antigen recognized by the patient's autoantibodies. To assess relevance and specificity of these antibodies to the identified targets as biomarkers of autoimmunity in movement disorders, autoantibody responses to the identified target were then measured by ELISA in various diseases of the central nervous system. Anti-aldolase A autoantibodies were associated mainly with HMD (7/17, 41%) and Parkinson's disease (4/30, 13%) patients, and undetectable in subjects with other inflammatory and non-inflammatory central nervous system diseases. We, thus, identified aldolase A as an autoantigen in a sub-group of patients with HMD, a clinically ill-defined syndrome. Anti-aldolase A antibodies may represent a useful biomarker of autoimmunity in HMD patients.

Cross-domain latent space projection for person re-identification

NASA Astrophysics Data System (ADS)

Pu, Nan; Wu, Song; Qian, Li; Xiao, Guoqiang

2018-04-01

In this paper, we research the problem of person re-identification and propose a cross-domain latent space projection (CDLSP) method to address the problems of the absence or insufficient labeled data in the target domain. Under the assumption that the visual features in the source domain and target domain share the similar geometric structure, we transform the visual features from source domain and target domain to a common latent space by optimizing the object function defined in the manifold alignment method. Moreover, the proposed object function takes into account the specific knowledge in the re-id with the aim to improve the performance of re-id under complex situations. Extensive experiments conducted on four benchmark datasets show the proposed CDLSP outperforms or is competitive with stateof- the-art methods for person re-identification.

Risk Factors Detection for Strategic Importance Objectives in Littoral Areas

NASA Astrophysics Data System (ADS)

Slămnoiu, G.; Radu, O.; Roşca, V.; Pascu, C.; Surdu, G.; Curcă, E.; Damian, R. G.; Rădulescu, A.

2017-06-01

With the invention and development of underwater explosive devices the need to neutralize them has also appeared, both for enemy and for own devices once conflicts are finished. The fight against active underwater explosive devices is a very complicated action that requires a very careful approach. Also, in the current context, strategic importance objectives located in the littoral areas can also become targets for divers or fast boats (suicidal actions).The system for detection, localization, tracking and identification of risk factors for strategic importance objectives in littoral areas has as one of its components an AUV and a hydro-acoustic sub-system for determining the ‘fingerprints’ of potential targets. The overall system will provide support for main missions such as underwater environment surveillance (detection, monitoring) in harbor areas and around other coast objectives, ship anchorage areas, mandatory pass points and also provide warnings about the presence of underwater and surface dangers in the interest areas.

The search for drug-targetable diagnostic, prognostic and predictive biomarkers in chronic graft-versus-host disease.

PubMed

Ren, Hong-Gang; Adom, Djamilatou; Paczesny, Sophie

2018-05-01

Chronic graft-versus-host disease (cGVHD) continues to be the leading cause of late morbidity and mortality after allogeneic hematopoietic stem cell transplantation (allo-HSCT), which is an increasingly applied curative method for both benign and malignant hematologic disorders. Biomarker identification is crucial for the development of noninvasive and cost-effective cGVHD diagnostic, prognostic, and predictive test for use in clinic. Furthermore, biomarkers may help to gain a better insight on ongoing pathophysiological processes. The recent widespread application of omics technologies including genomics, transcriptomics, proteomics and cytomics provided opportunities to discover novel biomarkers. Areas covered: This review focuses on biomarkers identified through omics that play a critical role in target identification for drug development, and that were verified in at least two independent cohorts. It also summarizes the current status on omics tools used to identify these useful cGVHD targets. We briefly list the biomarkers identified and verified so far. We further address challenges associated to their exploitation and application in the management of cGVHD patients. Finally, insights on biomarkers that are drug targetable and represent potential therapeutic targets are discussed. Expert commentary: We focus on biomarkers that play an essential role in target identification.

Large-scale identification of target proteins of a glycosyltransferase isozyme by Lectin-IGOT-LC/MS, an LC/MS-based glycoproteomic approach

PubMed Central

Sugahara, Daisuke; Kaji, Hiroyuki; Sugihara, Kazushi; Asano, Masahide; Narimatsu, Hisashi

2012-01-01

Model organisms containing deletion or mutation in a glycosyltransferase-gene exhibit various physiological abnormalities, suggesting that specific glycan motifs on certain proteins play important roles in vivo. Identification of the target proteins of glycosyltransferase isozymes is the key to understand the roles of glycans. Here, we demonstrated the proteome-scale identification of the target proteins specific for a glycosyltransferase isozyme, β1,4-galactosyltransferase-I (β4GalT-I). Although β4GalT-I is the most characterized glycosyltransferase, its distinctive contribution to β1,4-galactosylation has been hardly described so far. We identified a large number of candidates for the target proteins specific to β4GalT-I by comparative analysis of β4GalT-I-deleted and wild-type mice using the LC/MS-based technique with the isotope-coded glycosylation site-specific tagging (IGOT) of lectin-captured N-glycopeptides. Our approach to identify the target proteins in a proteome-scale offers common features and trends in the target proteins, which facilitate understanding of the mechanism that controls assembly of a particular glycan motif on specific proteins. PMID:23002422

Neurological Disease in Lupus: Toward a Personalized Medicine Approach

PubMed Central

McGlasson, Sarah; Wiseman, Stewart; Wardlaw, Joanna; Dhaun, Neeraj; Hunt, David P. J.

2018-01-01

The brain and nervous system are important targets for immune-mediated damage in systemic lupus erythematosus (SLE), resulting in a complex spectrum of neurological syndromes. Defining nervous system disease in lupus poses significant challenges. Among the difficulties to be addressed are a diversity of clinical manifestations and a lack of understanding of their mechanistic basis. However, despite these challenges, progress has been made in the identification of pathways which contribute to neurological disease in SLE. Understanding the molecular pathogenesis of neurological disease in lupus will inform both classification and approaches to clinical trials. PMID:29928273

Spectral imaging of chemical compounds using multivariate optically enhanced filters integrated with InGaAs VGA cameras

NASA Astrophysics Data System (ADS)

Priore, Ryan J.; Jacksen, Niels

2016-05-01

Infrared hyperspectral imagers (HSI) have been fielded for the detection of hazardous chemical and biological compounds, tag detection (friend versus foe detection) and other defense critical sensing missions over the last two decades. Low Size/Weight/Power/Cost (SWaPc) methods of identification of chemical compounds spectroscopy has been a long term goal for hand held applications. We describe a new HSI concept for low cost / high performance InGaAs SWIR camera chemical identification for military, security, industrial and commercial end user applications. Multivariate Optical Elements (MOEs) are thin-film devices that encode a broadband, spectroscopic pattern allowing a simple broadband detector to generate a highly sensitive and specific detection for a target analyte. MOEs can be matched 1:1 to a discrete analyte or class prediction. Additionally, MOE filter sets are capable of sensing an orthogonal projection of the original sparse spectroscopic space enabling a small set of MOEs to discriminate a multitude of target analytes. This paper identifies algorithms and broadband optical filter designs that have been demonstrated to identify chemical compounds using high performance InGaAs VGA detectors. It shows how some of the initial models have been reduced to simple spectral designs and tested to produce positive identification of such chemicals. We also are developing pixilated MOE compressed detection sensors for the detection of a multitude of chemical targets in challenging backgrounds/environments for both commercial and defense/security applications. This MOE based, real-time HSI sensor will exhibit superior sensitivity and specificity as compared to currently fielded HSI systems.

Identification of Hepatitis C Virus Inhibitors Targeting Different Aspects of Infection Using a Cell-Based Assay

PubMed Central

Yu, Xuemei; Sainz, Bruno; Petukhov, Pavel A.

2012-01-01

With 2 to 3% of the worldwide population chronically infected, hepatitis C virus (HCV) infection continues to be a major health care burden. Unfortunately, current interferon-based treatment options are not effective in all patients and are associated with significant side effects. Consequently, there is an ongoing need to identify and develop new anti-HCV therapies. Toward this goal, we previously developed a cell-based HCV infection assay for antiviral compound screening based on a low-multiplicity-of-infection approach that uniquely allows for the identification of antiviral compounds that target cell culture-derived HCV (HCVcc) at any step of the viral infection cycle. Using this assay, here we report the screening of the NCI Diversity Set II library, containing 1,974 synthesized chemical compounds, and the identification of compounds with specific anti-HCV activity. In combination with toxicity counterscreening, we identified 30 hits from the compound library, 13 of which showed reproducible and dose-dependent inhibition of HCV with mean therapeutic indices (50% cytotoxic concentration [CC50]/50% effective concentration [EC50]) of greater than 6. Using HCV pseudotype and replicon systems of multiple HCV genotypes, as well as infectious HCVcc-based assembly and secretion analysis, we determined that different compounds within this group of candidate inhibitors target different steps of viral infection. The compounds identified not only will serve as biological probes to study and further dissect the biology of viral infection but also should facilitate the development of new anti-HCV therapeutic treatments. PMID:22948883

50 CFR 622.60 - Adjustment of management measures.

Code of Federal Regulations, 2013 CFR

2013-10-01

... markings and identification, allowable biological catch (ABC) and ABC control rules, rebuilding plans, sale... harvested shrimp (maintaining shrimp in whole condition, use as bait), target effort and fishing mortality... identification, vessel markings and identification, ABC and ABC control rules, rebuilding plans, sale and...

50 CFR 622.60 - Adjustment of management measures.

Code of Federal Regulations, 2014 CFR

2014-10-01

... markings and identification, allowable biological catch (ABC) and ABC control rules, rebuilding plans, sale... harvested shrimp (maintaining shrimp in whole condition, use as bait), target effort and fishing mortality... identification, vessel markings and identification, ABC and ABC control rules, rebuilding plans, sale and...

Real-Time Reconnaissance-A Systems Look At Advanced Technology

NASA Astrophysics Data System (ADS)

Lapp, Henry

1981-12-01

An important role for reconnaissance is the location and identification of targets in real time. Current technology has been compartmented into sensors, automatic target recognizers, data links, ground exploitation and finally dissemination. In the days of bring home film recce, this segmentation of functions was appropriate. With the current emphasis on real time decision making from outputs of high resolution sensors this thinking has to be re-analyzed. A total systems approach to data management must be employed using the constraints imposed by technology as well as the atmosphere, survivable flight profiles, and the human workload. This paper will analyze the target acquisition through exploitation tasks and discuss the current advanced development technology that are applicable. A philosophy of processing data to get information as early as possible in the data handling chain is examined in the context of ground exploitation and dissemination needs. Examples of how the various real time sensors (screeners and processors), jam resistant data links and near real time ground data handling systems fit into this scenario are discussed. Specific DoD programs will be used to illustrate the credibility of this integrated approach.

Defining the uncertainty of electro-optical identification system performance estimates using a 3D optical environment derived from satellite

NASA Astrophysics Data System (ADS)

Ladner, S. D.; Arnone, R.; Casey, B.; Weidemann, A.; Gray, D.; Shulman, I.; Mahoney, K.; Giddings, T.; Shirron, J.

2009-05-01

Current United States Navy Mine-Counter-Measure (MCM) operations primarily use electro-optical identification (EOID) sensors to identify underwater targets after detection via acoustic sensors. These EOID sensors which are based on laser underwater imaging by design work best in "clear" waters and are limited in coastal waters especially with strong optical layers. Optical properties and in particular scattering and absorption play an important role on systems performance. Surface optical properties alone from satellite are not adequate to determine how well a system will perform at depth due to the existence of optical layers. The spatial and temporal characteristics of the 3d optical variability of the coastal waters along with strength and location of subsurface optical layers maximize chances of identifying underwater targets by exploiting optimum sensor deployment. Advanced methods have been developed to fuse the optical measurements from gliders, optical properties from "surface" satellite snapshot and 3-D ocean circulation models to extend the two-dimensional (2-D) surface satellite optical image into a three-dimensional (3-D) optical volume with subsurface optical layers. Modifications were made to an EOID performance model to integrate a 3-D optical volume covering an entire region of interest as input and derive system performance field. These enhancements extend present capability based on glider optics and EOID sensor models to estimate the system's "image quality". This only yields system performance information for a single glider profile location in a very large operational region. Finally, we define the uncertainty of the system performance by coupling the EOID performance model with the 3-D optical volume uncertainties. Knowing the ensemble spread of EOID performance field provides a new and unique capability for tactical decision makers and Navy Operations.

A novel surgical marking system for small peripheral lung nodules based on radio frequency identification technology: Feasibility study in a canine model.

PubMed

Kojima, Fumitsugu; Sato, Toshihiko; Takahata, Hiromi; Okada, Minoru; Sugiura, Tadao; Oshiro, Osamu; Date, Hiroshi; Nakamura, Tatsuo

2014-04-01

We investigated the feasibility and accuracy of a novel surgical marking system based on radiofrequency identification (RFID) technology for the localization of small peripheral lung nodules (SPLNs) in a canine model. The system consists of 4 components: (1) micro RFID tags (13.56 MHz, 1.0 × 1.0 × 0.8 mm), (2) a tag delivery system with a bronchoscope, (3) a wand-shaped locating probe (10-mm diameter), and (4) a signal processing unit with audio interface. Before the operation, pseudolesions mimicking SPLNs were prepared in 7 dogs by injecting colored collagen. By use of a computed tomographic (CT) guide, an RFID tag was placed via a bronchoscope close to each target lesion. This was then followed by scanning with the locating probe, and wedge resection was performed when possible. Operators can locate the tag by following the sound emitted by the system, which exhibits tone changes according to the tag-probe distance. The primary outcome measure was the rate of wedge resection with good margins. A total of 10 pseudolesions imitating SPLNs were selected as targets. During thoracoscopic procedures, 9 of 10 tags were detected by the system within a median of 27 seconds. Wedge resections were performed for these 9 lesions with a median margin of 11 mm. The single failure was caused by tag dislocation to the central airway. Successful localization and wedge resection of pseudolesions with appropriate margins were accomplished in an experimental setting. Our RFID marking system has future applications for accurately locating SPLNs in a clinical setting. Copyright © 2014 The American Association for Thoracic Surgery. Published by Mosby, Inc. All rights reserved.

Activity-based proteome profiling of potential cellular targets of Orlistat--an FDA-approved drug with anti-tumor activities.

PubMed

Yang, Peng-Yu; Liu, Kai; Ngai, Mun Hong; Lear, Martin J; Wenk, Markus R; Yao, Shao Q

2010-01-20

Orlistat, or tetrahydrolipstatin (THL), is an FDA-approved antiobesity drug with potential antitumor activities. Cellular off-targets and potential side effects of Orlistat in cancer therapies, however, have not been extensively explored thus far. In this study, we report the total of synthesis of THL-like protein-reactive probes, in which extremely conservative modifications (i.e., an alkyne handle) were introduced in the parental THL structure to maintain the native biological properties of Orlistat, while providing the necessary functionality for target identification via the bio-orthogonal click chemistry. With these natural productlike, cell-permeable probes, we were able to demonstrate, for the first time, this chemical proteomic approach is suitable for the identification of previously unknown cellular targets of Orlistat. In addition to the expected fatty acid synthase (FAS), we identified a total of eight new targets, some of which were further validated by experiments including Western blotting, recombinant protein expression, and site-directed mutagenesis. Our findings have important implications in the consideration of Orlistat as a potential anticancer drug at its early stages of development for cancer therapy. Our strategy should be broadly useful for off-target identification against quite a number of existing drugs and/or candidates, which are also covalent modifiers of their biological targets.

Remote sensing based on hyperspectral data analysis

NASA Astrophysics Data System (ADS)

Sharifahmadian, Ershad

In remote sensing, accurate identification of far objects, especially concealed objects is difficult. In this study, to improve object detection from a distance, the hyperspecral imaging and wideband technology are employed with the emphasis on wideband radar. As the wideband data includes a broad range of frequencies, it can reveal information about both the surface of the object and its content. Two main contributions are made in this study: 1) Developing concept of return loss for target detection: Unlike typical radar detection methods which uses radar cross section to detect an object, it is possible to enhance the process of detection and identification of concealed targets using the wideband radar based on the electromagnetic characteristics --conductivity, permeability, permittivity, and return loss-- of materials. During the identification process, collected wideband data is evaluated with information from wideband signature library which has already been built. In fact, several classes (e.g. metal, wood, etc.) and subclasses (ex. metals with high conductivity) have been defined based on their electromagnetic characteristics. Materials in a scene are then classified based on these classes. As an example, materials with high electrical conductivity can be conveniently detected. In fact, increasing relative conductivity leads to a reduction in the return loss. Therefore, metals with high conductivity (ex. copper) shows stronger radar reflections compared with metals with low conductivity (ex. stainless steel). Thus, it is possible to appropriately discriminate copper from stainless steel. 2) Target recognition techniques: To detect and identify targets, several techniques have been proposed, in particular the Multi-Spectral Wideband Radar Image (MSWRI) which is able to localize and identify concealed targets. The MSWRI is based on the theory of robust capon beamformer. During identification process, information from wideband signature library is utilized. The WB signature library includes such parameters as conductivity, permeability, permittivity, and return loss at different frequencies for possible materials related to a target. In the MSWRI approach, identification procedure is performed by calculating the RLs at different selected frequencies. Based on similarity of the calculated RLs and RL from WB signature library, targets are detected and identified. Based on the simulation and experimental results, it is concluded that the MSWRI technique is a promising approach for standoff target detection.

Target Control in Logical Models Using the Domain of Influence of Nodes.

PubMed

Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

2018-01-01

Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

Using modeling tools for implementing feasible land use and nature conservation governance systems in small islands - The Pico Island (Azores) case-study.

PubMed

Fernandes, J P; Freire, M; Guiomar, N; Gil, A

2017-03-15

The present study deals with the development of systematic conservation planning as management instrument in small oceanic islands, ensuring open systems of governance, and able to integrate an informed and involved participation of the stakeholders. Marxan software was used to define management areas according a set of alternative land use scenarios considering different conservation and management paradigms. Modeled conservation zones were interpreted and compared with the existing protected areas allowing more fused information for future trade-outs and stakeholder's involvement. The results, allowing the identification of Target Management Units (TMU) based on the consideration of different development scenarios proved to be consistent with a feasible development of evaluation approaches able to support sound governance systems. Moreover, the detailed geographic identification of TMU seems to be able to support participated policies towards a more sustainable management of the entire island. Copyright © 2016 Elsevier Ltd. All rights reserved.

Aptamers as tools for target prioritization and lead identification.

PubMed

Burgstaller, Petra; Girod, Anne; Blind, Michael

2002-12-15

The increasing number of potential drug target candidates has driven the development of novel technologies designed to identify functionally important targets and enhance the subsequent lead discovery process. Highly specific synthetic nucleic acid ligands--also known as aptamers--offer a new exciting route in the drug discovery process by linking target validation directly with HTS. Recently, aptamers have proven to be valuable tools for modulating the function of endogenous cellular proteins in their natural environment. A set of technologies has been developed to use these sophisticated ligands for the validation of potential drug targets in disease models. Moreover, aptamers that are specific antagonists of protein function can act as substitute interaction partners in HTS assays to facilitate the identification of small-molecule lead compounds.

Spectroscopic Characterization of Key Aromatic and Heterocyclic Molecules: A Route toward the Origin of Life

NASA Astrophysics Data System (ADS)

Puzzarini, Cristina; Baiardi, Alberto; Bloino, Julien; Barone, Vincenzo; Murphy, Thomas E.; Drew, H. Dennis; Ali, Ashraf

2017-09-01

To gain information on the abiotic synthesis of the building blocks of life from simple molecules, and their subsequent chemical evolution to biological systems, the starting point is the identification of target species in Titan-like planets; I.e., planets that resemble the primitive Earth, as well as in Earth-like planets in the habitable zone of their star, namely planets where life can be already originated. In this scenario, molecular spectroscopy plays a crucial role because spectroscopic signatures are at the basis of an unequivocal proof for the presence of these target molecules. Thanks to advances in many different techniques and NASA’s successful Kepler exoplanet transit mission, thousands of diverse planets outside of our solar system have been discovered. The James Webb Space Telescope (JWST), scheduled to be launched in 2018, will be very helpful in the identification of biosignature gases in Earth-like planets’ atmospheres and prebiotic molecule signatures in Titan-like atmospheres, by observing their absorption during transits. Although the search for key-target molecules in exoplanet atmospheres can be carried out by the JWST Transit Spectroscopy in the infrared (IR) region (0.6-29 μm wavelength range), opportunities for their detection in protostellar cores, protoplanetary disks, and on Titan are also offered by interferometric high spectral and spatial resolution observations using the Atacama Large Millimeter/submillimeter Array. In the present work, target molecules have been selected, and their spectroscopic characterization presented in view of supporting their infrared and complementary millimeter/submillimeter-wave spectral observations. In detail, the selected target molecules include: (1) the three-membered oxygen-containing heterocycles, oxirane and protonated oxirane; (2) the cyclopropenyl cation and its methyl derivative; (3) two examples of ortho- and peri-fused tri-cyclic aromatic rings, I.e., the phenalenyl cation ({{{C}}}13{{{{H}}}9}+) and anion ({{{C}}}13{{{{H}}}9}-); and (4) uracil, a specific RNA base.

Spectroscopic Characterization of Key Aromatic Molecules: A Route toward The Origin of Life.

PubMed

Puzzarini, Cristina; Baiardi, Alberto; Bloino, Julien; Barone, Vincenzo; Murphy, Thomas E; Drew, Dennis; Ali, Ashraf

2017-08-04

To gain information on the abiotic synthesis of the building blocks of life from simple molecules, and their subsequent chemical evolution to biological systems, the starting point is the identification of target species in Titan-like planets, i.e., planets that resemble the primitive Earth, as well as in Earth-like planets in the habitable zone of their star, namely planets where life can be already originated. In this scenario, molecular spectroscopy plays a crucial role because spectroscopic signatures are at the basis of an unequivocal proof for the presence of these target molecules. Thanks to the advances in many different techniques and to the NASA successful Kepler exoplanet transit mission, thousands of diverse planets outside of our solar system have been discovered. The James Webb Space Telescope (JWST), scheduled to be launched in 2018, will be very helpful in the identification of biosignature gases in Earth-like planets' atmospheres and of prebiotic molecule signatures in Titan-like atmospheres by observing their absorption during transits. While the search for key-target molecules in exoplanet atmospheres can be carried out by the JWST Transit Spectroscopy in the infrared (IR) region (0.6 - 29 µm wavelength range), opportunities for their detection in protostellar cores, protoplanetary disks and on Titan are also offered by the interferometric high spectral and spatial resolution observations using the Atacama Large Millimeter/submillimeter Array (ALMA). In the present work, target molecules have been selected and their spectroscopic characterization presented in view of supporting their infrared and complementary millimeter/submillimeter-wave spectral observations. In detail, the selected target molecules include: (1) the three-membered oxygen-containing heterocycles: oxirane and protonated oxirane, (2) the cyclopropenyl cation and its methyl derivative, (3) two examples of ortho- and peri-fused tri-cyclic aromatic rings, i.e., the phenalenyl cation (C 13 H 9 + ) and anion (C 13 H 9 -), and (4) uracil, a specific RNA base.

Investigation of α-MnO 2 Tunneled Structures as Model Cation Hosts for Energy Storage

DOE PAGES

Housel, Lisa M.; Wang, Lei; Abraham, Alyson; ...

2018-02-19

Future advances in energy storage systems rely on identification of appropriate target materials and deliberate synthesis of the target materials with control of their physiochemical properties in order to disentangling the contributions of distinct properties to the functional electrochemistry. Furthermore, this goal demands systematic inquiry using model materials that provide the opportunity for significant synthetic versatility and control. Ideally, a material family that enables direct manipulation of characteristics including composition, defects and crystallite size while remaining within the defined structural framework would be necessary. Accomplishing this through direct synthetic methods is desirable to minimize the complicating effects of secondary processing.

High resolution spectrograph. [for LST

NASA Technical Reports Server (NTRS)

Peacock, K.

1975-01-01

The high resolution spectrograph (HRS) is designed to be used with the Large Space Telescope (LST) for the study of spectra of point and extended targets in the spectral range 110 to 410 nm. It has spectral resolutions of 1,000; 30,000; and 100,000 and has a field of view as large as 10 arc sec. The spectral range and resolution are selectable using interchangeable optical components and an echelle spectrograph is used to display a cross dispersed spectrum on the photocathode of either of 2 SEC orthicon image tubes. Provisions are included for wavelength calibration, target identification and acquisition and thermal control. The system considerations of the instrument are described.

Investigation of α-MnO 2 Tunneled Structures as Model Cation Hosts for Energy Storage

DOE Office of Scientific and Technical Information (OSTI.GOV)

Housel, Lisa M.; Wang, Lei; Abraham, Alyson

Future advances in energy storage systems rely on identification of appropriate target materials and deliberate synthesis of the target materials with control of their physiochemical properties in order to disentangling the contributions of distinct properties to the functional electrochemistry. Furthermore, this goal demands systematic inquiry using model materials that provide the opportunity for significant synthetic versatility and control. Ideally, a material family that enables direct manipulation of characteristics including composition, defects and crystallite size while remaining within the defined structural framework would be necessary. Accomplishing this through direct synthetic methods is desirable to minimize the complicating effects of secondary processing.

Systemic sclerosis and localized scleroderma--current concepts and novel targets for therapy.

PubMed

Distler, Oliver; Cozzio, Antonio

2016-01-01

Systemic sclerosis (SSc) is a chronic autoimmune disease with a high morbidity and mortality. Skin and organ fibrosis are key manifestations of SSc, for which no generally accepted therapy is available. Thus, there is a high unmet need for novel anti-fibrotic therapeutic strategies in SSc. At the same time, important progress has been made in the identification and characterization of potential molecular targets in fibrotic diseases over the recent years. In this review, we have selected four targeted therapies, which are tested in clinical trials in SSc, for in depths discussion of their preclinical characterization. Soluble guanylate cyclase (sGC) stimulators such as riociguat might target both vascular remodeling and tissue fibrosis. Blockade of interleukin-6 might be particularly promising for early inflammatory stages of SSc. Inhibition of serotonin receptor 2b signaling links platelet activation to tissue fibrosis. Targeting simultaneously multiple key molecules with the multityrosine kinase-inhibitor nintedanib might be a promising approach in complex fibrotic diseases such as SSc, in which many partially independent pathways are activated. Herein, we also give a state of the art overview of the current classification, clinical presentation, diagnostic approach, and treatment options of localized scleroderma. Finally, we discuss whether the novel targeted therapies currently tested in SSc could be used for localized scleroderma.

Toward Repurposing Metformin as a Precision Anti-Cancer Therapy Using Structural Systems Pharmacology

PubMed Central

Hart, Thomas; Dider, Shihab; Han, Weiwei; Xu, Hua; Zhao, Zhongming; Xie, Lei

2016-01-01

Metformin, a drug prescribed to treat type-2 diabetes, exhibits anti-cancer effects in a portion of patients, but the direct molecular and genetic interactions leading to this pleiotropic effect have not yet been fully explored. To repurpose metformin as a precision anti-cancer therapy, we have developed a novel structural systems pharmacology approach to elucidate metformin’s molecular basis and genetic biomarkers of action. We integrated structural proteome-scale drug target identification with network biology analysis by combining structural genomic, functional genomic, and interactomic data. Through searching the human structural proteome, we identified twenty putative metformin binding targets and their interaction models. We experimentally verified the interactions between metformin and our top-ranked kinase targets. Notably, kinases, particularly SGK1 and EGFR were identified as key molecular targets of metformin. Subsequently, we linked these putative binding targets to genes that do not directly bind to metformin but whose expressions are altered by metformin through protein-protein interactions, and identified network biomarkers of phenotypic response of metformin. The molecular targets and the key nodes in genetic networks are largely consistent with the existing experimental evidence. Their interactions can be affected by the observed cancer mutations. This study will shed new light into repurposing metformin for safe, effective, personalized therapies. PMID:26841718

Comprehensive viral enrichment enables sensitive respiratory virus genomic identification and analysis by next generation sequencing.

PubMed

O'Flaherty, Brigid M; Li, Yan; Tao, Ying; Paden, Clinton R; Queen, Krista; Zhang, Jing; Dinwiddie, Darrell L; Gross, Stephen M; Schroth, Gary P; Tong, Suxiang

2018-06-01

Next generation sequencing (NGS) technologies have revolutionized the genomics field and are becoming more commonplace for identification of human infectious diseases. However, due to the low abundance of viral nucleic acids (NAs) in relation to host, viral identification using direct NGS technologies often lacks sufficient sensitivity. Here, we describe an approach based on two complementary enrichment strategies that significantly improves the sensitivity of NGS-based virus identification. To start, we developed two sets of DNA probes to enrich virus NAs associated with respiratory diseases. The first set of probes spans the genomes, allowing for identification of known viruses and full genome sequencing, while the second set targets regions conserved among viral families or genera, providing the ability to detect both known and potentially novel members of those virus groups. Efficiency of enrichment was assessed by NGS testing reference virus and clinical samples with known infection. We show significant improvement in viral identification using enriched NGS compared to unenriched NGS. Without enrichment, we observed an average of 0.3% targeted viral reads per sample. However, after enrichment, 50%-99% of the reads per sample were the targeted viral reads for both the reference isolates and clinical specimens using both probe sets. Importantly, dramatic improvements on genome coverage were also observed following virus-specific probe enrichment. The methods described here provide improved sensitivity for virus identification by NGS, allowing for a more comprehensive analysis of disease etiology. © 2018 O'Flaherty et al.; Published by Cold Spring Harbor Laboratory Press.

Providing Agility in C2 Environments Through Networked Information Processing: A Model of Expertise

DTIC Science & Technology

2014-06-01

personal benefits promoting self-esteem, pride, self-efficacy, personal identification with colleagues and organizations, obtaining a better...studies based on staged-event methods with “target-present” and “target-absent” lineups . The results show that when choosers make positive... identification , the correlation between confidence and accuracy was consistently high. Besides correct choosers have a higher mean confidence level than

Duplex Identification of Staphylococcus aureus by Aptamer and Gold Nanoparticles.

PubMed

Chang, Tianjun; Wang, Libo; Zhao, Kexu; Ge, Yu; He, Meng; Li, Gang

2016-06-01

Staphylococcus aureus is the top common pathogen causing infections and food poisoning. Identification of S. aureus is crucial for the disease diagnosis and regulation of food hygiene. Herein, we report an aptamer-AuNPs based method for duplex identification of S. aureus. Using AuNPs as an indicator, SA23, an aptamer against S. aureus, can well identify its target from Escherichia coli, Listeria monocytogenes and Pseudomonas aeruginosa. Furthermore, we find citrate-coated AuNPs can strongly bind to S. aureus, but not bind to Salmonella enterica and Proteus mirabilis, which leads to different color changes in salt solution. This colorimetric response is capable of distinguishing S. aureus from S. enteritidis and P. mirabilis. Thus, using the aptasensor and AuNPs together, S. aureus can be accurately identified from the common pathogens. This duplex identification system is a promising platform for simple visual identification of S. aureus. Additionally, in the aptasensing process, bacteria are incubated with aptamers and then be removed before the aptamers adding to AuNPs, which may avoid the interactions between bacteria and AuNPs. This strategy can be potentially applied in principle to detect other cells by AuNPs-based aptasensors.

Defining Human Failure Events for Petroleum Risk Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Ronald L. Boring; Knut Øien

2014-06-01

In this paper, an identification and description of barriers and human failure events (HFEs) for human reliability analysis (HRA) is performed. The barriers, called target systems, are identified from risk significant accident scenarios represented as defined situations of hazard and accident (DSHAs). This report serves as the foundation for further work to develop petroleum HFEs compatible with the SPAR-H method and intended for reuse in future HRAs.

An Investigation into the Impact of School Context on Achievement: A Situational Analysis of Five Western Cape Schools in South Africa

ERIC Educational Resources Information Center

Mushayikwa, Emmanuel

2009-01-01

The purpose of this study was to generate a snapshot profile of the teaching and learning environment in each of five schools in Cape Town, South Africa. The generated profile would in turn facilitate the identification of critical, localized and systemic factors that might be targeted by a whole school intervention programme to improve the…

A Comprehensive Approach in Dissemination of Evidence-Based Care for PTSD

DTIC Science & Technology

2012-09-01

been published, to provide evidence-based resources to facilitate practice evaluation and identification of potential gaps in care. In order to...practice’s capacity to provide evidence-based care and identify potential gaps in care as targets for improvement. Finally, strategies to implement...existing patients, the PIP tools can inform improvement efforts at the clinician-, practice-or systems-level, facilitate detection of potential gaps in

A protocol for the simultaneous identification of chitin-containing particles and their associated bacteria.

PubMed

Biancalana, Florencia; Kopprio, Germán A; Lara, Rubén J; Alonso, Cecilia

2017-07-01

Chitin is the second most abundant polymer on Earth, playing a crucial role in the biogeochemical cycles. A core issue for studying its processing in aquatic systems is the identification and enumeration of chitin-containing particles and organisms, ideally in a manner that can be directly linked to bulk chitin quantification. The aim of this study was the development of such a technique. We successfully combined the methodology of bulk chitin determination using wheat germ agglutinin (FITC-WGA) for staining chitin-containing particles and organisms along with CARD-FISH staining of either chitin-containing eukaryotic cells or bacteria associated with them. Environmental chitin staining was successfully applied to natural water samples. Fungal hyphae, diatoms, and dinoflagellates, sestonic aggregates and chitin-containing structures derived from metazoa were observed. Also, hybridized bacteria attached to chitinaceous debris were clearly visualized. Finally, as proof of principle, cultured yeast cells were simultaneously-targeted by FITC-WGA and the EUK516 probe without exhibiting any interference between both stains. The presented approach appears as a powerful tool to evaluate the contribution of different size classes and organisms to chitin production and consumption, opening the possibility for application of single-cell approaches targeting the ecophysiology of chitin transformations in aquatic systems. Copyright © 2017 Elsevier GmbH. All rights reserved.

Identification and functional analysis of choline transporter in tongue cancer: A novel molecular target for tongue cancer therapy.

PubMed

Nishiyama, Ryohta; Nagashima, Fumiaki; Iwao, Beniko; Kawai, Yuiko; Inoue, Kana; Midori, Arisa; Yamanaka, Tsuyoshi; Uchino, Hiroyuki; Inazu, Masato

2016-06-01

We examined the functional characteristics of choline uptake in human tongue carcinoma using the cell line HSC-3. Furthermore, we explored the possible correlation between the inhibition of choline uptake and apoptotic cell death. Both choline transporter-like protein 1 (CTL1) and CTL2 mRNAs and proteins were expressed, and were located in plasma membrane and mitochondria, respectively. Choline uptake was saturable and mediated by a single transport system, which is pH-dependent. Several cationic drugs inhibited cell viability and [(3)H]choline uptake. Choline uptake inhibitors and choline deficiency inhibited cell viability and increased caspase-3/7 activity. We conclude that extracellular choline is mainly transported via a CTL1 that relies on a directed H(+) gradient as a driving force. The functional inhibition of CTL1 by cationic drugs could promote apoptotic cell death. Furthermore, CTL2 may be the major site for the control of choline oxidation in mitochondria and hence for the supply of endogenous betaine and S-adenosyl methionine, which serves as a major methyl donor. Identification of this CTL1- and CTL2-mediated choline transport system provides a potential new target for tongue cancer therapy. Copyright © 2016 The Authors. Production and hosting by Elsevier B.V. All rights reserved.

Fault detection and identification in missile system guidance and control: a filtering approach

NASA Astrophysics Data System (ADS)

Padgett, Mary Lou; Evers, Johnny; Karplus, Walter J.

1996-03-01

Real-world applications of computational intelligence can enhance the fault detection and identification capabilities of a missile guidance and control system. A simulation of a bank-to- turn missile demonstrates that actuator failure may cause the missile to roll and miss the target. Failure of one fin actuator can be detected using a filter and depicting the filter output as fuzzy numbers. The properties and limitations of artificial neural networks fed by these fuzzy numbers are explored. A suite of networks is constructed to (1) detect a fault and (2) determine which fin (if any) failed. Both the zero order moment term and the fin rate term show changes during actuator failure. Simulations address the following questions: (1) How bad does the actuator failure have to be for detection to occur, (2) How bad does the actuator failure have to be for fault detection and isolation to occur, (3) are both zero order moment and fine rate terms needed. A suite of target trajectories are simulated, and properties and limitations of the approach reported. In some cases, detection of the failed actuator occurs within 0.1 second, and isolation of the failure occurs 0.1 after that. Suggestions for further research are offered.

Evaluation of the maximum-likelihood adaptive neural system (MLANS) applications to noncooperative IFF

NASA Astrophysics Data System (ADS)

Chernick, Julian A.; Perlovsky, Leonid I.; Tye, David M.

1994-06-01

This paper describes applications of maximum likelihood adaptive neural system (MLANS) to the characterization of clutter in IR images and to the identification of targets. The characterization of image clutter is needed to improve target detection and to enhance the ability to compare performance of different algorithms using diverse imagery data. Enhanced unambiguous IFF is important for fratricide reduction while automatic cueing and targeting is becoming an ever increasing part of operations. We utilized MLANS which is a parametric neural network that combines optimal statistical techniques with a model-based approach. This paper shows that MLANS outperforms classical classifiers, the quadratic classifier and the nearest neighbor classifier, because on the one hand it is not limited to the usual Gaussian distribution assumption and can adapt in real time to the image clutter distribution; on the other hand MLANS learns from fewer samples and is more robust than the nearest neighbor classifiers. Future research will address uncooperative IFF using fused IR and MMW data.

Unsupervised Spatial Event Detection in Targeted Domains with Applications to Civil Unrest Modeling

PubMed Central

Zhao, Liang; Chen, Feng; Dai, Jing; Hua, Ting; Lu, Chang-Tien; Ramakrishnan, Naren

2014-01-01

Twitter has become a popular data source as a surrogate for monitoring and detecting events. Targeted domains such as crime, election, and social unrest require the creation of algorithms capable of detecting events pertinent to these domains. Due to the unstructured language, short-length messages, dynamics, and heterogeneity typical of Twitter data streams, it is technically difficult and labor-intensive to develop and maintain supervised learning systems. We present a novel unsupervised approach for detecting spatial events in targeted domains and illustrate this approach using one specific domain, viz. civil unrest modeling. Given a targeted domain, we propose a dynamic query expansion algorithm to iteratively expand domain-related terms, and generate a tweet homogeneous graph. An anomaly identification method is utilized to detect spatial events over this graph by jointly maximizing local modularity and spatial scan statistics. Extensive experiments conducted in 10 Latin American countries demonstrate the effectiveness of the proposed approach. PMID:25350136

Targeted therapy in biliary tract cancers-current limitations and potentials in the future.

PubMed

Sahu, Selley; Sun, Weijing

2017-04-01

Biliary tract cancers (BTC)/Cholangiocarcinoma (CCA) is an aggressive biliary tract epithelial malignancy from varying locations within the biliary tree with cholangiocyte depreciation., including intrahepatic cholangiocarcinoma (iCCA) (iCCA), extrahepatic cholangiocarcinoma (eCCA) and gallbladder carcinoma (GBC). The disease is largely heterogeneous in etiology, epidemiology, and molecular profile. There are limited treatment options and low survival rates for those patients with advanced or metastatic disease. Systemic treatment is confined to cytotoxic chemotherapy with the combination of gemcitabine and cisplatin. Lack of a stereotype genetic signature makes difficult in identification of potential actionable target directly, which may also explain lack of obvious clinic benefit with target oriented agents from current studies. It is crucial to understand of BTC carcinogenesis, tumor-stroma interactions, and key molecular pathways, and herald to establish targeted, individualized therapies for the heterogeneous disease, and eventually to improve the survival and overall outcome of patients.

Ships and Maritime Targets Observation Campaigns Using Available C- and X-Band SAR Satellite

NASA Astrophysics Data System (ADS)

Velotto, Domenico; Bentes, Carlos; Lehner, Susanne

2015-04-01

Obviously, radar resolution and swath width are two very important factors when it comes to synthetic aperture radar (SAR) maritime targets detections. The dilemma of using single polarization SAR imagery with higher resolution and coverage or quad- (or dual- polarimetric) imagery with its richness of information, is still unsolved when it comes to this application.In the framework of ESA project MARISS and EU project DOLPHIN, in situ campaigns aimed at solving this dilemma have been carried out. Single and multi- polarimetric SAR data acquired by TerraSAR-X, RADARSAT-2 and COSMO-SkyMed have been acquired with close time gaps and partial coverage overlap. In this way several moving and non-moving maritime targets have been imaged with different polarization, geometry and working frequency. Available ground truth reports provided by Automatic Identification System (AIS) data, nautical chart and wind farm location are used to validate the different types of maritime targets.

An integrated control scheme for space robot after capturing non-cooperative target

NASA Astrophysics Data System (ADS)

Wang, Mingming; Luo, Jianjun; Yuan, Jianping; Walter, Ulrich

2018-06-01

How to identify the mass properties and eliminate the unknown angular momentum of space robotic system after capturing a non-cooperative target is of great challenge. This paper focuses on designing an integrated control framework which includes detumbling strategy, coordination control and parameter identification. Firstly, inverted and forward chain approaches are synthesized for space robot to obtain dynamic equation in operational space. Secondly, a detumbling strategy is introduced using elementary functions with normalized time, while the imposed end-effector constraints are considered. Next, a coordination control scheme for stabilizing both base and end-effector based on impedance control is implemented with the target's parameter uncertainty. With the measurements of the forces and torques exerted on the target, its mass properties are estimated during the detumbling process accordingly. Simulation results are presented using a 7 degree-of-freedom kinematically redundant space manipulator, which verifies the performance and effectiveness of the proposed method.

Solid phase sequencing of biopolymers

DOEpatents

Cantor, Charles; Koster, Hubert

2010-09-28

This invention relates to methods for detecting and sequencing target nucleic acid sequences, to mass modified nucleic acid probes and arrays of probes useful in these methods, and to kits and systems which contain these probes. Useful methods involve hybridizing the nucleic acids or nucleic acids which represent complementary or homologous sequences of the target to an array of nucleic acid probes. These probes comprise a single-stranded portion, an optional double-stranded portion and a variable sequence within the single-stranded portion. The molecular weights of the hybridized nucleic acids of the set can be determined by mass spectroscopy, and the sequence of the target determined from the molecular weights of the fragments. Nucleic acids whose sequences can be determined include DNA or RNA in biological samples such as patient biopsies and environmental samples. Probes may be fixed to a solid support such as a hybridization chip to facilitate automated molecular weight analysis and identification of the target sequence.

Limitations of contrast enhancement for infrared target identification

NASA Astrophysics Data System (ADS)

Du Bosq, Todd W.; Fanning, Jonathan D.

2009-05-01

Contrast enhancement and dynamic range compression are currently being used to improve the performance of infrared imagers by increasing the contrast between the target and the scene content. Automatic contrast enhancement techniques do not always achieve this improvement. In some cases, the contrast can increase to a level of target saturation. This paper assesses the range-performance effects of contrast enhancement for target identification as a function of image saturation. Human perception experiments were performed to determine field performance using contrast enhancement on the U.S. Army RDECOM CERDEC NVESD standard military eight target set using an un-cooled LWIR camera. The experiments compare the identification performance of observers viewing contrast enhancement processed images at various levels of saturation. Contrast enhancement is modeled in the U.S. Army thermal target acquisition model (NVThermIP) by changing the scene contrast temperature. The model predicts improved performance based on any improved target contrast, regardless of specific feature saturation or enhancement. The measured results follow the predicted performance based on the target task difficulty metric used in NVThermIP for the non-saturated cases. The saturated images reduce the information contained in the target and performance suffers. The model treats the contrast of the target as uniform over spatial frequency. As the contrast is enhanced, the model assumes that the contrast is enhanced uniformly over the spatial frequencies. After saturation, the spatial cues that differentiate one tank from another are located in a limited band of spatial frequencies. A frequency dependent treatment of target contrast is needed to predict performance of over-processed images.

Analysis of the infrared detection system operating range based on polarization degree

NASA Astrophysics Data System (ADS)

Jiang, Kai; Liu, Wen; Liu, Kai; Duan, Jing; Yan, Pei-pei; Shan, Qiu-sha

2018-02-01

Infrared polarization detection technology has unique advantages in the field of target detection and identification because of using the polarization information of radiation. The mechanism of infrared polarization is introduced. Comparing with traditional infrared detection distance model, infrared detection operating range and Signal to Noise Ratio (SNR) model is built according to the polarization degree and noise. The influence of polarization degree on the SNR of infrared system is analyzed. At last, the basic condition of polarization detection SNR better than traditional infrared detection SNR is obtained.

Methods for decoding Cas9 protospacer adjacent motif (PAM) sequences: A brief overview.

PubMed

Karvelis, Tautvydas; Gasiunas, Giedrius; Siksnys, Virginijus

2017-05-15

Recently the Cas9, an RNA guided DNA endonuclease, emerged as a powerful tool for targeted genome manipulations. Cas9 protein can be reprogrammed to cleave, bind or nick any DNA target by simply changing crRNA sequence, however a short nucleotide sequence, termed PAM, is required to initiate crRNA hybridization to the DNA target. PAM sequence is recognized by Cas9 protein and must be determined experimentally for each Cas9 variant. Exploration of Cas9 orthologs could offer a diversity of PAM sequences and novel biochemical properties that may be beneficial for genome editing applications. Here we briefly review and compare Cas9 PAM identification assays that can be adopted for other PAM-dependent CRISPR-Cas systems. Copyright © 2017 Elsevier Inc. All rights reserved.

Blueprint for antimicrobial hit discovery targeting metabolic networks

PubMed Central

Shen, Y.; Liu, J.; Estiu, G.; Isin, B.; Ahn, Y-Y.; Lee, D-S.; Barabási, A-L.; Kapatral, V.; Wiest, O.; Oltvai, Z. N.

2010-01-01

Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy. PMID:20080587

Automatic de-identification of textual documents in the electronic health record: a review of recent research

PubMed Central

2010-01-01

Background In the United States, the Health Insurance Portability and Accountability Act (HIPAA) protects the confidentiality of patient data and requires the informed consent of the patient and approval of the Internal Review Board to use data for research purposes, but these requirements can be waived if data is de-identified. For clinical data to be considered de-identified, the HIPAA "Safe Harbor" technique requires 18 data elements (called PHI: Protected Health Information) to be removed. The de-identification of narrative text documents is often realized manually, and requires significant resources. Well aware of these issues, several authors have investigated automated de-identification of narrative text documents from the electronic health record, and a review of recent research in this domain is presented here. Methods This review focuses on recently published research (after 1995), and includes relevant publications from bibliographic queries in PubMed, conference proceedings, the ACM Digital Library, and interesting publications referenced in already included papers. Results The literature search returned more than 200 publications. The majority focused only on structured data de-identification instead of narrative text, on image de-identification, or described manual de-identification, and were therefore excluded. Finally, 18 publications describing automated text de-identification were selected for detailed analysis of the architecture and methods used, the types of PHI detected and removed, the external resources used, and the types of clinical documents targeted. All text de-identification systems aimed to identify and remove person names, and many included other types of PHI. Most systems used only one or two specific clinical document types, and were mostly based on two different groups of methodologies: pattern matching and machine learning. Many systems combined both approaches for different types of PHI, but the majority relied only on pattern matching, rules, and dictionaries. Conclusions In general, methods based on dictionaries performed better with PHI that is rarely mentioned in clinical text, but are more difficult to generalize. Methods based on machine learning tend to perform better, especially with PHI that is not mentioned in the dictionaries used. Finally, the issues of anonymization, sufficient performance, and "over-scrubbing" are discussed in this publication. PMID:20678228

Automatic de-identification of textual documents in the electronic health record: a review of recent research.

PubMed

Meystre, Stephane M; Friedlin, F Jeffrey; South, Brett R; Shen, Shuying; Samore, Matthew H

2010-08-02

In the United States, the Health Insurance Portability and Accountability Act (HIPAA) protects the confidentiality of patient data and requires the informed consent of the patient and approval of the Internal Review Board to use data for research purposes, but these requirements can be waived if data is de-identified. For clinical data to be considered de-identified, the HIPAA "Safe Harbor" technique requires 18 data elements (called PHI: Protected Health Information) to be removed. The de-identification of narrative text documents is often realized manually, and requires significant resources. Well aware of these issues, several authors have investigated automated de-identification of narrative text documents from the electronic health record, and a review of recent research in this domain is presented here. This review focuses on recently published research (after 1995), and includes relevant publications from bibliographic queries in PubMed, conference proceedings, the ACM Digital Library, and interesting publications referenced in already included papers. The literature search returned more than 200 publications. The majority focused only on structured data de-identification instead of narrative text, on image de-identification, or described manual de-identification, and were therefore excluded. Finally, 18 publications describing automated text de-identification were selected for detailed analysis of the architecture and methods used, the types of PHI detected and removed, the external resources used, and the types of clinical documents targeted. All text de-identification systems aimed to identify and remove person names, and many included other types of PHI. Most systems used only one or two specific clinical document types, and were mostly based on two different groups of methodologies: pattern matching and machine learning. Many systems combined both approaches for different types of PHI, but the majority relied only on pattern matching, rules, and dictionaries. In general, methods based on dictionaries performed better with PHI that is rarely mentioned in clinical text, but are more difficult to generalize. Methods based on machine learning tend to perform better, especially with PHI that is not mentioned in the dictionaries used. Finally, the issues of anonymization, sufficient performance, and "over-scrubbing" are discussed in this publication.

Rapid identification of bacteria from positive blood culture bottles by use of matrix-assisted laser desorption-ionization time of flight mass spectrometry fingerprinting.

PubMed

Christner, Martin; Rohde, Holger; Wolters, Manuel; Sobottka, Ingo; Wegscheider, Karl; Aepfelbacher, Martin

2010-05-01

Early and adequate antimicrobial therapy has been shown to improve the clinical outcome in bloodstream infections (BSI). To provide rapid pathogen identification for targeted treatment, we applied matrix-assisted laser desorption-ionization time of flight (MALDI-TOF) mass spectrometry fingerprinting to bacteria directly recovered from blood culture bottles. A total of 304 aerobic and anaerobic blood cultures, reported positive by a Bactec 9240 system, were subjected in parallel to differential centrifugation with subsequent mass spectrometry fingerprinting and reference identification using established microbiological methods. A representative spectrum of bloodstream pathogens was recovered from 277 samples that grew a single bacterial isolate. Species identification by direct mass spectrometry fingerprinting matched reference identification in 95% of these samples and worked equally well for aerobic and anaerobic culture bottles. Application of commonly used score cutoffs to classify the fingerprinting results led to an identification rate of 87%. Mismatching mostly resulted from insufficient bacterial numbers and preferentially occurred with Gram-positive samples. The respective spectra showed low concordance to database references and were effectively rejected by score thresholds. Spiking experiments and examination of the respective study samples even suggested applicability of the method to mixed cultures. With turnaround times around 100 min, the approach allowed for reliable pathogen identification at the day of blood culture positivity, providing treatment-relevant information within the critical phase of septic illness.

Commercial-Aircraft Protection System

NASA Astrophysics Data System (ADS)

Case, Russell L., Jr.; Wolff, Peter H.

2004-09-01

Recent world events have identified needs for a commercial aircraft defense system against Man-Portable Air Defense Systems (MANPADS), such as SA-7 and Stinger shoulder launched surface-to-air missiles. Technical challenges include target detection, identification and countermeasures. Political and societal challenges include cost, time to deployment, ground and air safety, and reliability. These challenges, as well as many others, have been met and overcome with the development of Thor Systems' Commercial-Aircraft Protection System (C-APS). C-APS makes use of commercial technology such as radar and infrared sensors with a laser-based countermeasure. Unlike adapted military systems, C-APS detects the threat long before the military versions by employing a 360 degree hemispherical scan, identifying the threat with an infrared sensor and employing a directed laser to not only deflect the target but to permanently disable its seeker. Enhanced capabilities include multiple threat elimination and closed-loop technology for kill verification. All of this is accomplished with development costs less than half that required to convert military technology, manufacturing costs significantly less than competitive products, and a maintenance cycle coincident with standard FAA requirements, which are significantly longer than current systems.

Use of in vivo Expression Technology for the Identification of Putative Host Adaptation Factors of the Lyme Disease Spirochete.

PubMed

Casselli, Timothy; Bankhead, Troy

2015-01-01

The causative agent of Lyme disease, Borrelia burgdorferi, is an obligate parasite that requires either a tick vector or a mammalian host for survival. Identification of the bacterial genes that are specifically expressed during infection of the mammalian host could provide targets for novel therapeutics and vaccines. In vivo expression technology (IVET) is a reporter-based promoter trap system that utilizes selectable markers to identify promoters of bacterial host-specific genes. Using previously characterized genes for in vivo and in vitro selection, this study utilized an IVET system that allows for selection of B. burgdorferi sequences that act as active promoters only during murine infection. This promoter trap system was able to successfully distinguish active promoter sequences both in vivo and in vitro from control sequences and a library of cloned B. burgdorferi genomic fragments. However, a bottleneck effect during the experimental mouse infection limited the utility for genome-wide promoter screening. Overall, IVET was demonstrated as a tool for the identification of in vivo-induced promoter elements of B. burgdorferi, and the observed infection bottleneck apparent using a polyclonal infection pool provides insight into the dynamics of experimental infection with B. burgdorferi. © 2015 S. Karger AG, Basel.

Artificial lunar impact craters: Four new identifications, part I

NASA Technical Reports Server (NTRS)

Whitaker, E. A.

1972-01-01

The Apollo 16 panoramic camera photographed the impact locations of the Ranger 7 and 9 spacecraft and the S-4B stage of the Apollo 14 Saturn launch vehicle. Identification of the Ranger craters was very simple because each photographed its target point before impact. Identification of the S-4B impact crater proved to be a simple matter because the impact location, as derived from earth-based tracking, displayed a prominent and unique system of mixed light and dark rays. By using the criterion of a dark ray pattern, a reexamination of the Apollo 14 500 mm Hasselblad sequence taken of the Apollo 13 S-4B impact area was made. This examination quickly led to the discovery of the ray system and the impact crater. The study of artificial lunar impact craters, ejecta blankets, and ray systems provides the long-needed link between the various experimental terrestrial impact and explosion craters, and the naturally occurring impact craters on the moon. This elementary study shows that lunar impact crater diameters are closely predictable from a knowledge of the energies involved, at least in the size range considered, and suggests that parameters, such as velocity, may have a profound effect on crater morphology and ejecta blanket albedo.

Systems pharmacology-based drug discovery for marine resources: an example using sea cucumber (Holothurians).

PubMed

Guo, Yingying; Ding, Yan; Xu, Feifei; Liu, Baoyue; Kou, Zinong; Xiao, Wei; Zhu, Jingbo

2015-05-13

Sea cucumber, a kind of marine animal, have long been utilized as tonic and traditional remedies in the Middle East and Asia because of its effectiveness against hypertension, asthma, rheumatism, cuts and burns, impotence, and constipation. In this study, an overall study performed on sea cucumber was used as an example to show drug discovery from marine resource by using systems pharmacology model. The value of marine natural resources has been extensively considered because these resources can be potentially used to treat and prevent human diseases. However, the discovery of drugs from oceans is difficult, because of complex environments in terms of composition and active mechanisms. Thus, a comprehensive systems approach which could discover active constituents and their targets from marine resource, understand the biological basis for their pharmacological properties is necessary. In this study, a feasible pharmacological model based on systems pharmacology was established to investigate marine medicine by incorporating active compound screening, target identification, and network and pathway analysis. As a result, 106 candidate components of sea cucumber and 26 potential targets were identified. Furthermore, the functions of sea cucumber in health improvement and disease treatment were elucidated in a holistic way based on the established compound-target and target-disease networks, and incorporated pathways. This study established a novel strategy that could be used to explore specific active mechanisms and discover new drugs from marine sources. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

ERPs reveal subliminal processing of fearful faces.

PubMed

Kiss, Monika; Eimer, Martin

2008-03-01

To investigate whether facial expression is processed in the absence of conscious awareness, ERPs were recorded in a task in which participants had to identify the expression of masked fearful and neutral target faces. On supraliminal trials (200 ms target duration), in which identification performance was high, a sustained positivity to fearful versus neutral target faces started 140 ms after target face onset. On subliminal trials (8 ms target duration), identification performance was at chance level, but ERPs still showed systematic fear-specific effects. An early positivity to fearful target faces was present but smaller than on supraliminal trials. A subsequent enhanced N2 to fearful faces was only present for subliminal trials. In contrast, a P3 enhancement to fearful faces was observed on supraliminal but not subliminal trials. Results demonstrate rapid emotional expression processing in the absence of awareness.

ERPs reveal subliminal processing of fearful faces

PubMed Central

Kiss, Monika; Eimer, Martin

2008-01-01

To investigate whether facial expression is processed in the absence of conscious awareness, ERPs were recorded in a task where participants had to identify the expression of masked fearful and neutral target faces. On supraliminal trials (200 ms target duration), where identification performance was high, a sustained positivity to fearful versus neutral target faces started 140 ms after target face onset. On subliminal trials (8 ms target duration), identification performance was at chance level, but ERPs still showed systematic fear-specific effects. An early positivity to fearful target faces was present but smaller than on supraliminal trials. A subsequent enhanced N2 to fearful faces was only present for subliminal trials. In contrast, a P3 enhancement to fearful faces was observed on supraliminal but not subliminal trials. Results demonstrate rapid emotional expression processing in the absence of awareness. PMID:17995905

RISC RNA sequencing for context-specific identification of in vivo microRNA targets.

PubMed

Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

2011-01-07

MicroRNAs (miRs) are expanding our understanding of cardiac disease and have the potential to transform cardiovascular therapeutics. One miR can target hundreds of individual mRNAs, but existing methodologies are not sufficient to accurately and comprehensively identify these mRNA targets in vivo. To develop methods permitting identification of in vivo miR targets in an unbiased manner, using massively parallel sequencing of mouse cardiac transcriptomes in combination with sequencing of mRNA associated with mouse cardiac RNA-induced silencing complexes (RISCs). We optimized techniques for expression profiling small amounts of RNA without introducing amplification bias and applied this to anti-Argonaute 2 immunoprecipitated RISCs (RISC-Seq) from mouse hearts. By comparing RNA-sequencing results of cardiac RISC and transcriptome from the same individual hearts, we defined 1645 mRNAs consistently targeted to mouse cardiac RISCs. We used this approach in hearts overexpressing miRs from Myh6 promoter-driven precursors (programmed RISC-Seq) to identify 209 in vivo targets of miR-133a and 81 in vivo targets of miR-499. Consistent with the fact that miR-133a and miR-499 have widely differing "seed" sequences and belong to different miR families, only 6 targets were common to miR-133a- and miR-499-programmed hearts. RISC-sequencing is a highly sensitive method for general RISC profiling and individual miR target identification in biological context and is applicable to any tissue and any disease state.

Multi-Stage System for Automatic Target Recognition

NASA Technical Reports Server (NTRS)

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

2010-01-01

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 feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an artificial neural network classifier. The multi-stage system allows tuning the detection sensitivity and the identification specificity individually in each stage. It is easier to achieve optimized ATR operation based on its specific goal. The test results show that the system was successful in substantially reducing the false positive rate when tested on a sonar and video image datasets.

Nuclear Security: Target Analysis

DOE Office of Scientific and Technical Information (OSTI.GOV)

Singh, Surinder Paul; Gibbs, Philip W.; Bultz, Garl A.

2014-03-01

This objectives of this session were to understand the basic steps of target identification; describe the SNRI targets in detail; characterize specific targets with more detail; prioritize targets based on guidance documents; understand the graded safeguards concept; identify roll up and understand why it is a concern; and recognize the category for different materials.

DYRK1B as therapeutic target in Hedgehog/GLI-dependent cancer cells with Smoothened inhibitor resistance

PubMed Central

Gruber, Wolfgang; Hutzinger, Martin; Elmer, Dominik Patrick; Parigger, Thomas; Sternberg, Christina; Cegielkowski, Lukasz; Zaja, Mirko; Leban, Johann; Michel, Susanne; Hamm, Svetlana; Vitt, Daniel; Aberger, Fritz

2016-01-01

A wide range of human malignancies displays aberrant activation of Hedgehog (HH)/GLI signaling, including cancers of the skin, brain, gastrointestinal tract and hematopoietic system. Targeting oncogenic HH/GLI signaling with small molecule inhibitors of the essential pathway effector Smoothened (SMO) has shown remarkable therapeutic effects in patients with advanced and metastatic basal cell carcinoma. However, acquired and de novo resistance to SMO inhibitors poses severe limitations to the use of SMO antagonists and urgently calls for the identification of novel targets and compounds. Here we report on the identification of the Dual-Specificity-Tyrosine-Phosphorylation-Regulated Kinase 1B (DYRK1B) as critical positive regulator of HH/GLI signaling downstream of SMO. Genetic and chemical inhibition of DYRK1B in human and mouse cancer cells resulted in marked repression of HH signaling and GLI1 expression, respectively. Importantly, DYRK1B inhibition profoundly impaired GLI1 expression in both SMO-inhibitor sensitive and resistant settings. We further introduce a novel small molecule DYRK1B inhibitor, DYRKi, with suitable pharmacologic properties to impair SMO-dependent and SMO-independent oncogenic GLI activity. The results support the use of DYRK1B antagonists for the treatment of HH/GLI-associated cancers where SMO inhibitors fail to demonstrate therapeutic efficacy. PMID:26784250

Descriptions and identifications of strangers by youth and adult eyewitnesses.

PubMed

Pozzulo, Joanna D; Warren, Kelly L

2003-04-01

Two studies varying target gender and mode of target exposure were conducted to compare the quantity, nature, and accuracy of free recall person descriptions provided by youths and adults. In addition, the relation among age, identification accuracy, and number of descriptors reported was considered. Youths (10-14 years) reported fewer descriptors than adults. Exterior facial descriptors (e.g., hair items) were predominant and accurately reported by youths and adults. Accuracy was consistently problematic for youths when reporting body descriptors (e.g., height, weight) and interior facial features. Youths reported a similar number of descriptors when making accurate versus inaccurate identification decisions. This pattern also was consistent for adults. With target-absent lineups, the difference in the number of descriptors reported between adults and youths was greater when making a false positive versus correct rejection.

Sensors for isolation of anti-cancer compounds found within marine invertebrates

NASA Astrophysics Data System (ADS)

Wiegand, Gordon; LaRue, Amanda

2015-05-01

Highly evolved bacteria living within immobile marine animals are being targeted as a source of antitumor pharmaceuticals. This paper describes 2 electo-optical sensor systems developed for identifying species of tunicates and actinobacteria that live within them. Two stages of identification include 1) a benthic survey apparatus to locate species and 2) a laboratory housed cell analysis platform used to classify their bacterial micro-biome. Marine Optics Sampling- There are over 3000 species of Tunicates that thrive in diverse habitats. We use a system of cameras, GPS and the GPS/photo integration application on a PC laptop to compile a time / location stamp for each image taken during the dive survey. A shape-map of x/y coordinates of photos are stored for later identification and sampling. Flow Cytometers/cell sorters housed at The Medical University of South Carolina and The University of Maryland have been modified to produce low-noise, high signal wave forms used for bacteria analysis. We strive to describe salient contrasts between these two fundamentally different sensor systems. Accents are placed on analog transducers and initial step sensing systems and output.

Indel-seq: a fast-forward genetics approach for identification of trait-associated putative candidate genomic regions and its application in pigeonpea (Cajanus cajan).

PubMed

Singh, Vikas K; Khan, Aamir W; Saxena, Rachit K; Sinha, Pallavi; Kale, Sandip M; Parupalli, Swathi; Kumar, Vinay; Chitikineni, Annapurna; Vechalapu, Suryanarayana; Sameer Kumar, Chanda Venkata; Sharma, Mamta; Ghanta, Anuradha; Yamini, Kalinati Narasimhan; Muniswamy, Sonnappa; Varshney, Rajeev K

2017-07-01

Identification of candidate genomic regions associated with target traits using conventional mapping methods is challenging and time-consuming. In recent years, a number of single nucleotide polymorphism (SNP)-based mapping approaches have been developed and used for identification of candidate/putative genomic regions. However, in the majority of these studies, insertion-deletion (Indel) were largely ignored. For efficient use of Indels in mapping target traits, we propose Indel-seq approach, which is a combination of whole-genome resequencing (WGRS) and bulked segregant analysis (BSA) and relies on the Indel frequencies in extreme bulks. Deployment of Indel-seq approach for identification of candidate genomic regions associated with fusarium wilt (FW) and sterility mosaic disease (SMD) resistance in pigeonpea has identified 16 Indels affecting 26 putative candidate genes. Of these 26 affected putative candidate genes, 24 genes showed effect in the upstream/downstream of the genic region and two genes showed effect in the genes. Validation of these 16 candidate Indels in other FW- and SMD-resistant and FW- and SMD-susceptible genotypes revealed a significant association of five Indels (three for FW and two for SMD resistance). Comparative analysis of Indel-seq with other genetic mapping approaches highlighted the importance of the approach in identification of significant genomic regions associated with target traits. Therefore, the Indel-seq approach can be used for quick and precise identification of candidate genomic regions for any target traits in any crop species. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

Identification of MAPK Substrates Using Quantitative Phosphoproteomics.

PubMed

Zhang, Tong; Schneider, Jacqueline D; Zhu, Ning; Chen, Sixue

2017-01-01

Activation of mitogen-activated protein kinases (MAPKs) under diverse biotic and abiotic factors and identification of an array of downstream MAPK target proteins are hot topics in plant signal transduction. Through interactions with a plethora of substrate proteins, MAPK cascades regulate many physiological processes in the course of plant growth, development, and response to environmental factors. Identification and quantification of potential MAPK substrates are essential, but have been technically challenging. With the recent advancement in phosphoproteomics, here we describe a method that couples metal dioxide for phosphopeptide enrichment with tandem mass tags (TMT) mass spectrometry (MS) for large-scale MAPK substrate identification and quantification. We have applied this method to a transient expression system carrying a wild type (WT) and a constitutive active (CA) version of a MAPK. This combination of genetically engineered MAPKs and phosphoproteomics provides a high-throughput, unbiased analysis of MAPK-triggered phosphorylation changes on the proteome scale. Therefore, it is a robust method for identifying potential MAPK substrates and should be applicable in the study of other kinase cascades in plants as well as in other organisms.

Validation of a newly developed hexaplex real-time PCR assay for screening for presence of GMOs in food, feed and seed.

PubMed

Bahrdt, C; Krech, A B; Wurz, A; Wulff, D

2010-03-01

For years, an increasing number and diversity of genetically modified plants has been grown on a commercial scale. The need for detection and identification of these genetically modified organisms (GMOs) calls for broad and at the same time flexible high throughput testing methods. Here we describe the development and validation of a hexaplex real-time polymerase chain reaction (PCR) screening assay covering more than 100 approved GMOs containing at least one of the GMO targets of the assay. The assay comprises detection systems for Cauliflower Mosaic Virus 35S promoter, Agrobacterium tumefaciens NOS terminator, Figwort Mosaic Virus 34S promoter and two construct-specific sequences present in novel genetically modified soybean and maize that lack common screening elements. Additionally a detection system for an internal positive control (IPC) indicating the presence or absence of PCR inhibiting substances was included. The six real-time PCR systems were allocated to five detection channels showing no significant crosstalk between the detection channels. As part of an extensive validation, a limit of detection (LOD(abs)) < or = ten target copies was proven in hexaplex format. A sensitivity < or = ten target copies of each GMO detection system was still shown in highly asymmetric target situations in the presence of 1,000 copies of all other GMO targets of each detection channel. Furthermore, the applicability to a broad sample spectrum and reliable indication of inhibition by the IPC system was demonstrated. The presented hexaplex assay offers sensitive and reliable detection of GMOs in processed and unprocessed food, feed and seed samples with high efficiency.

Characterizing Perceptual Performance at Multiple Discrimination Precisions in External Noise

PubMed Central

Jeon, Seong-Taek; Lu, Zhong-Lin; Dosher, Barbara Anne

2010-01-01

Existing observer models developed for studies with the external noise paradigm are strictly only applicable to target detection or identification/discrimination of orthogonal target(s). We elaborated the perceptual template model (PTM) to account for contrast thresholds in identifying non-orthogonal targets. Full contrast psychometric functions were measured in an orientation identification task with four orientation differences across a wide range of external noise levels. We showed that observer performance can be modeled by the elaborated PTM with two templates that correspond to the two stimulus categories. Sampling efficiencies of the human observers were also estimated. The elaborated PTM provides a theoretical framework to characterize joint feature and contrast sensitivity of human observers. PMID:19884915

MEASURE: An integrated data-analysis and model identification facility

NASA Technical Reports Server (NTRS)

Singh, Jaidip; Iyer, Ravi K.

1990-01-01

The first phase of the development of MEASURE, an integrated data analysis and model identification facility is described. The facility takes system activity data as input and produces as output representative behavioral models of the system in near real time. In addition a wide range of statistical characteristics of the measured system are also available. The usage of the system is illustrated on data collected via software instrumentation of a network of SUN workstations at the University of Illinois. Initially, statistical clustering is used to identify high density regions of resource-usage in a given environment. The identified regions form the states for building a state-transition model to evaluate system and program performance in real time. The model is then solved to obtain useful parameters such as the response-time distribution and the mean waiting time in each state. A graphical interface which displays the identified models and their characteristics (with real time updates) was also developed. The results provide an understanding of the resource-usage in the system under various workload conditions. This work is targeted for a testbed of UNIX workstations with the initial phase ported to SUN workstations on the NASA, Ames Research Center Advanced Automation Testbed.

Targeting of Repeated Sequences Unique to a Gene Results in Significant Increases in Antisense Oligonucleotide Potency

PubMed Central

Vickers, Timothy A.; Freier, Susan M.; Bui, Huynh-Hoa; Watt, Andrew; Crooke, Stanley T.

2014-01-01

A new strategy for identifying potent RNase H-dependent antisense oligonucleotides (ASOs) is presented. Our analysis of the human transcriptome revealed that a significant proportion of genes contain unique repeated sequences of 16 or more nucleotides in length. Activities of ASOs targeting these repeated sites in several representative genes were compared to those of ASOs targeting unique single sites in the same transcript. Antisense activity at repeated sites was also evaluated in a highly controlled minigene system. Targeting both native and minigene repeat sites resulted in significant increases in potency as compared to targeting of non-repeated sites. The increased potency at these sites is a result of increased frequency of ASO/RNA interactions which, in turn, increases the probability of a productive interaction between the ASO/RNA heteroduplex and human RNase H1 in the cell. These results suggest a new, highly efficient strategy for rapid identification of highly potent ASOs. PMID:25334092

Novel toggle-rate based energy-efficient scheme for heavy load real-time IM-DD OFDM-PON with ONU LLID identification in time-domain using amplitude decision.

PubMed

Qin, Youxiang; Zhang, Junjie

2017-07-10

A novel low complexity and energy-efficient scheme by controlling the toggle-rate of ONU with time-domain amplitude identification is proposed for a heavy load downlink in an intensity-modulation and direct-detection orthogonal frequency division multiplexing passive optical network (IM-DD OFDM-PON). In a conventional OFDM-PON downlink, all ONUs have to perform demodulation for all the OFDM frames in a broadcast way no matter whether the frames are targeted to or not, which causes a huge energy waste. However, in our scheme, the optical network unit (ONU) logical link identifications (LLIDs) are inserted into each downlink OFDM frame in time-domain at the optical line terminal (OLT) side. At the ONU side, the LLID is obtained with a low complexity and high precision amplitude identification method. The ONU sets the toggle-rate of demodulation module to zero when the frames are not targeted to, which avoids unnecessary digital signal processing (DSP) energy consumption. Compared with the sleep-mode methods consisting of clock recovery and synchronization, toggle-rate shows its advantage in fast changing, which is more suitable for the heavy load scenarios. Moreover, for the first time to our knowledge, the characteristics of the proposed scheme are investigated in a real-time IM-DD OFDM system, which performs well at the received optical power as low as -21dBm. The experimental results show that 25.1% energy consumption can be saved in the receiver compared to the conventional configurations.

Mechanistic models enable the rational use of in vitro drug-target binding kinetics for better drug effects in patients.

PubMed

de Witte, Wilhelmus E A; Wong, Yin Cheong; Nederpelt, Indira; Heitman, Laura H; Danhof, Meindert; van der Graaf, Piet H; Gilissen, Ron A H J; de Lange, Elizabeth C M

2016-01-01

Drug-target binding kinetics are major determinants of the time course of drug action for several drugs, as clearly described for the irreversible binders omeprazole and aspirin. This supports the increasing interest to incorporate newly developed high-throughput assays for drug-target binding kinetics in drug discovery. A meaningful application of in vitro drug-target binding kinetics in drug discovery requires insight into the relation between in vivo drug effect and in vitro measured drug-target binding kinetics. In this review, the authors discuss both the relation between in vitro and in vivo measured binding kinetics and the relation between in vivo binding kinetics, target occupancy and effect profiles. More scientific evidence is required for the rational selection and development of drug-candidates on the basis of in vitro estimates of drug-target binding kinetics. To elucidate the value of in vitro binding kinetics measurements, it is necessary to obtain information on system-specific properties which influence the kinetics of target occupancy and drug effect. Mathematical integration of this information enables the identification of drug-specific properties which lead to optimal target occupancy and drug effect in patients.

Eyewitness accuracy rates in police showup and lineup presentations: a meta-analytic comparison.

PubMed

Steblay, Nancy; Dysart, Jennifer; Fulero, Solomon; Lindsay, R C

2003-10-01

Meta-analysis is used to compare identification accuracy rates in showups and lineups. Eight papers were located, providing 12 tests of the hypothesis and including 3013 participants. Results indicate that showups generate lower choosing rates than lineups. In target present conditions, showups and lineups yield approximately equal hit rates, and in target absent conditions, showups produce a significantly higher level of correct rejections. False identification rates are approximately equal in showups and lineups when lineup foil choices are excluded from analysis. Dangerous false identifications are more numerous for showups when an innocent suspect resembles the perpetrator. Function of lineup foils, assessment strategies for false identifications, and the potential impact of biases in lineup practice are suggested as additional considerations in evaluation of showup versus lineup efficacy.

Robust 3D Position Estimation in Wide and Unconstrained Indoor Environments

PubMed Central

Mossel, Annette

2015-01-01

In this paper, a system for 3D position estimation in wide, unconstrained indoor environments is presented that employs infrared optical outside-in tracking of rigid-body targets with a stereo camera rig. To overcome limitations of state-of-the-art optical tracking systems, a pipeline for robust target identification and 3D point reconstruction has been investigated that enables camera calibration and tracking in environments with poor illumination, static and moving ambient light sources, occlusions and harsh conditions, such as fog. For evaluation, the system has been successfully applied in three different wide and unconstrained indoor environments, (1) user tracking for virtual and augmented reality applications, (2) handheld target tracking for tunneling and (3) machine guidance for mining. The results of each use case are discussed to embed the presented approach into a larger technological and application context. The experimental results demonstrate the system’s capabilities to track targets up to 100 m. Comparing the proposed approach to prior art in optical tracking in terms of range coverage and accuracy, it significantly extends the available tracking range, while only requiring two cameras and providing a relative 3D point accuracy with sub-centimeter deviation up to 30 m and low-centimeter deviation up to 100 m. PMID:26694388

Characterizing protein domain associations by Small-molecule ligand binding

PubMed Central

Li, Qingliang; Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

2012-01-01

Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing. PMID:23745168

The Statistical Analysis Techniques to Support the NGNP Fuel Performance Experiments

DOE Office of Scientific and Technical Information (OSTI.GOV)

Bihn T. Pham; Jeffrey J. Einerson

2010-06-01

This paper describes the development and application of statistical analysis techniques to support the AGR experimental program on NGNP fuel performance. The experiments conducted in the Idaho National Laboratory’s Advanced Test Reactor employ fuel compacts placed in a graphite cylinder shrouded by a steel capsule. The tests are instrumented with thermocouples embedded in graphite blocks and the target quantity (fuel/graphite temperature) is regulated by the He-Ne gas mixture that fills the gap volume. Three techniques for statistical analysis, namely control charting, correlation analysis, and regression analysis, are implemented in the SAS-based NGNP Data Management and Analysis System (NDMAS) for automatedmore » processing and qualification of the AGR measured data. The NDMAS also stores daily neutronic (power) and thermal (heat transfer) code simulation results along with the measurement data, allowing for their combined use and comparative scrutiny. The ultimate objective of this work includes (a) a multi-faceted system for data monitoring and data accuracy testing, (b) identification of possible modes of diagnostics deterioration and changes in experimental conditions, (c) qualification of data for use in code validation, and (d) identification and use of data trends to support effective control of test conditions with respect to the test target. Analysis results and examples given in the paper show the three statistical analysis techniques providing a complementary capability to warn of thermocouple failures. It also suggests that the regression analysis models relating calculated fuel temperatures and thermocouple readings can enable online regulation of experimental parameters (i.e. gas mixture content), to effectively maintain the target quantity (fuel temperature) within a given range.« less

Identification of cells initiating human melanomas.

PubMed

Schatton, Tobias; Murphy, George F; Frank, Natasha Y; Yamaura, Kazuhiro; Waaga-Gasser, Ana Maria; Gasser, Martin; Zhan, Qian; Jordan, Stefan; Duncan, Lyn M; Weishaupt, Carsten; Fuhlbrigge, Robert C; Kupper, Thomas S; Sayegh, Mohamed H; Frank, Markus H

2008-01-17

Tumour-initiating cells capable of self-renewal and differentiation, which are responsible for tumour growth, have been identified in human haematological malignancies and solid cancers. If such minority populations are associated with tumour progression in human patients, specific targeting of tumour-initiating cells could be a strategy to eradicate cancers currently resistant to systemic therapy. Here we identify a subpopulation enriched for human malignant-melanoma-initiating cells (MMIC) defined by expression of the chemoresistance mediator ABCB5 (refs 7, 8) and show that specific targeting of this tumorigenic minority population inhibits tumour growth. ABCB5+ tumour cells detected in human melanoma patients show a primitive molecular phenotype and correlate with clinical melanoma progression. In serial human-to-mouse xenotransplantation experiments, ABCB5+ melanoma cells possess greater tumorigenic capacity than ABCB5- bulk populations and re-establish clinical tumour heterogeneity. In vivo genetic lineage tracking demonstrates a specific capacity of ABCB5+ subpopulations for self-renewal and differentiation, because ABCB5+ cancer cells generate both ABCB5+ and ABCB5- progeny, whereas ABCB5- tumour populations give rise, at lower rates, exclusively to ABCB5- cells. In an initial proof-of-principle analysis, designed to test the hypothesis that MMIC are also required for growth of established tumours, systemic administration of a monoclonal antibody directed at ABCB5, shown to be capable of inducing antibody-dependent cell-mediated cytotoxicity in ABCB5+ MMIC, exerted tumour-inhibitory effects. Identification of tumour-initiating cells with enhanced abundance in more advanced disease but susceptibility to specific targeting through a defining chemoresistance determinant has important implications for cancer therapy.

New concepts of fluorescent probes for specific detection of DNA sequences: bis-modified oligonucleotides in excimer and exciplex detection.

PubMed

Gbaj, A; Bichenkova, Ev; Walsh, L; Savage, He; Sardarian, Ar; Etchells, Ll; Gulati, A; Hawisa, S; Douglas, Kt

2009-12-01

The detection of single base mismatches in DNA is important for diagnostics, treatment of genetic diseases, and identification of single nucleotide polymorphisms. Highly sensitive, specific assays are needed to investigate genetic samples from patients. The use of a simple fluorescent nucleoside analogue in detection of DNA sequence and point mutations by hybridisation in solution is described in this study. The 5'-bispyrene and 3'-naphthalene oligonucleotide probes form an exciplex on hybridisation to target in water and the 5'-bispyrene oligonucleotide alone is an adequate probe to determine concentration of target present. It was also indicated that this system has a potential to identify mismatches and insertions. The aim of this work was to investigate experimental structures and conditions that permit strong exciplex emission for nucleic acid detectors, and show how such exciplexes can register the presence of mismatches as required in SNP analysis. This study revealed that the hybridisation of 5'-bispyrenyl fluorophore to a DNA target results in formation of a fluorescent probe with high signal intensity change and specificity for detecting a complementary target in a homogeneous system. Detection of SNP mutations using this split-probe system is a highly specific, simple, and accessible method to meet the rigorous requirements of pharmacogenomic studies. Thus, it is possible for the system to act as SNP detectors and it shows promise for future applications in genetic testing.

24/7 security system: 60-FPS color EMCCD camera with integral human recognition

NASA Astrophysics Data System (ADS)

Vogelsong, T. L.; Boult, T. E.; Gardner, D. W.; Woodworth, R.; Johnson, R. C.; Heflin, B.

2007-04-01

An advanced surveillance/security system is being developed for unattended 24/7 image acquisition and automated detection, discrimination, and tracking of humans and vehicles. The low-light video camera incorporates an electron multiplying CCD sensor with a programmable on-chip gain of up to 1000:1, providing effective noise levels of less than 1 electron. The EMCCD camera operates in full color mode under sunlit and moonlit conditions, and monochrome under quarter-moonlight to overcast starlight illumination. Sixty frame per second operation and progressive scanning minimizes motion artifacts. The acquired image sequences are processed with FPGA-compatible real-time algorithms, to detect/localize/track targets and reject non-targets due to clutter under a broad range of illumination conditions and viewing angles. The object detectors that are used are trained from actual image data. Detectors have been developed and demonstrated for faces, upright humans, crawling humans, large animals, cars and trucks. Detection and tracking of targets too small for template-based detection is achieved. For face and vehicle targets the results of the detection are passed to secondary processing to extract recognition templates, which are then compared with a database for identification. When combined with pan-tilt-zoom (PTZ) optics, the resulting system provides a reliable wide-area 24/7 surveillance system that avoids the high life-cycle cost of infrared cameras and image intensifiers.

Selecting among competing models of electro-optic, infrared camera system range performance

USGS Publications Warehouse

Nichols, Jonathan M.; Hines, James E.; Nichols, James D.

2013-01-01

Range performance is often the key requirement around which electro-optical and infrared camera systems are designed. This work presents an objective framework for evaluating competing range performance models. Model selection based on the Akaike’s Information Criterion (AIC) is presented for the type of data collected during a typical human observer and target identification experiment. These methods are then demonstrated on observer responses to both visible and infrared imagery in which one of three maritime targets was placed at various ranges. We compare the performance of a number of different models, including those appearing previously in the literature. We conclude that our model-based approach offers substantial improvements over the traditional approach to inference, including increased precision and the ability to make predictions for some distances other than the specific set for which experimental trials were conducted.

Specific features of goal setting in road traffic safety

NASA Astrophysics Data System (ADS)

Kolesov, V. I.; Danilov, O. F.; Petrov, A. I.

2017-10-01

Road traffic safety (RTS) management is inherently a branch of cybernetics and therefore requires clear formalization of the task. The paper aims at identification of the specific features of goal setting in RTS management under the system approach. The paper presents the results of cybernetic modeling of the cause-to-effect mechanism of a road traffic accident (RTA); in here, the mechanism itself is viewed as a complex system. A designed management goal function is focused on minimizing the difficulty in achieving the target goal. Optimization of the target goal has been performed using the Lagrange principle. The created working algorithms have passed the soft testing. The key role of the obtained solution in the tactical and strategic RTS management is considered. The dynamics of the management effectiveness indicator has been analyzed based on the ten-year statistics for Russia.

Identification of computer-generated facial composites.

PubMed

Kovera, M B; Penrod, S D; Pappas, C; Thill, D L

1997-04-01

Two studies examined the effectiveness of the Mac-a-Mug Pro, a computerized facial composite production system. In the first study, college freshmen prepared from memory composites of other students and faculty from their former high schools. Other students who had attended the same high schools could not recognize the composites of either students or faculty members when the composites of individuals known to them (n = 10) were mixed with composites of a large number (n = 40) of strangers. Neither preparer familiarity with the target, preparer-assessed composite quality, nor viewer familiarity predicted composite recognition. Study 2 indicated that naive witnesses who viewed the composites could not select the people depicted in the composites from photo lineups (1 target and 4 foils). The results raise questions about the efficacy of composite systems as tools to promote recognition of suspects in criminal contexts.

Coherent Doppler lidar for automated space vehicle rendezvous, stationkeeping and capture

NASA Technical Reports Server (NTRS)

Bilbro, James A.

1991-01-01

The inherent spatial resolution of laser radar makes ladar or lidar an attractive candidate for Automated Rendezvous and Capture application. Previous applications were based on incoherent lidar techniques, requiring retro-reflectors on the target vehicle. Technology improvements (reduced size, no cryogenic cooling requirement) have greatly enhanced the construction of coherent lidar systems. Coherent lidar permits the acquisition of non-cooperative targets at ranges that are limited by the detection capability rather than by the signal-to-noise ratio (SNR) requirements. The sensor can provide translational state information (range, velocity, and angle) by direct measurement and, when used with any array detector, also can provide attitude information by Doppler imaging techniques. Identification of the target is accomplished by scanning with a high pulse repetition frequency (dependent on the SNR). The system performance is independent of range and should not be constrained by sun angle. An initial effort to characterize a multi-element detection system has resulted in a system that is expected to work to a minimum range of 1 meter. The system size, weight and power requirements are dependent on the operating range; 10 km range requires a diameter of 3 centimeters with overall size at 3 x 3 x 15 to 30 cm, while 100 km range requires a 30 cm diameter.

Type 1 diabetes: prospective cohort studies for identification of the environmental trigger.

PubMed

Rønningen, Kjersti S

2013-12-01

Type 1 diabetes (T1D) is one of the most common chronic diseases with childhood onset, and the disease incidence has increased two to fivefold over the past half century by as yet unknown means. T1D occurs when the body's immune system turns against itself, destroying in a very specific and targeted way-the pancreatic β-cells. T1D results from poorly defined interactions between susceptibility genes and environmental determinants. In contrast to the rapid progress in finding T1D genes, identification and confirmation of environmental determinants remain a formidable challenge. This review article will give an overview of ongoing prospective cohort studies aiming to identify the environmental trigger(s) causing T1D.

The influence of camouflage, obstruction, familiarity and spatial ability on target identification from an unmanned ground vehicle.

PubMed

Fincannon, Thomas; Keebler, Joseph R; Jentsch, Florian; Curtis, Michael

2013-01-01

The purpose of this study was to examine the effects of environmental and cognitive factors on the identification of targets from an unmanned ground vehicle (UGV). This was accomplished by manipulating obstruction, camouflage and familiarity of objects in the environment, while also measuring spatial ability. The effects of these variables on target identification were studied by measuring performance of participants that observed pre-recorded video from a 1:35 scaled military operations in urban terrain facility. Analyses indicated that a combination of camouflage and obstruction caused the most detrimental effects on performance, and that there were differences in the recognition of familiar and unfamiliar targets. Further analysis indicated that these detrimental effects could only be overcome with a combination of target familiarity and spatial ability. The findings highlight the degree to which environmental factors hinder performance and the need for a multidimensional approach for improving performance under these conditions. Areas in need of future research are also discussed. Cognitive theory is applied to the problem of perception from UGVs. Results from an experimental study indicate that a combination of camouflage and obstruction caused the most detrimental effects on performance, with differences in the recognition of both familiar and unfamiliar targets. Familiarity and spatial ability interacted to predict the performance.

Categorization and identification of simultaneous targets.

PubMed

Theeuwes, J

1991-02-01

Early and late selection theories of visual attention disagree about whether identification occurs before or after selection. Studies showing the category effect, i.e., the time to detect a letter is hardly affected by the number of digits present in the display, are taken as evidence for late selection theories since these studies suggest parallel identification of all items in the display. As an extension of previous studies, in the present study two categorically different targets were presented simultaneously among a variable number of nontargets. Subjects were shown brief displays of two target letters among either 2, 4 or 6 nontarget digits. Subjects responded 'same' when the two letters were identical and 'different' otherwise. Since the 'same-different' response reflects the combined outcome of the simultaneous targets, late-selection theory predicts that the time to match the target letters is independent of the number of nontarget digits. Alternatively, early-selection theory predicts a linear increase of reaction time with display size since the presence of more than one target disrupts parallel preattentive processing, leading to a serial search through all items in the display. The results provide evidence for the early-selection view since reaction time increased linearly with the number of categorically different nontargets. A control experiment revealed that none of the alternative explanations could account for the display size effect.

Rapid Detection of the Chlamydiaceae and Other Families in the Order Chlamydiales: Three PCR Tests

PubMed Central

Everett, Karin D. E.; Hornung, Linda J.; Andersen, Arthur A.

1999-01-01

Few identification methods will rapidly or specifically detect all bacteria in the order Chlamydiales, family Chlamydiaceae. In this study, three PCR tests based on sequence data from over 48 chlamydial strains were developed for identification of these bacteria. Two tests exclusively recognized the Chlamydiaceae: a multiplex test targeting the ompA gene and the rRNA intergenic spacer and a TaqMan test targeting the 23S ribosomal DNA. The multiplex test was able to detect as few as 200 inclusion-forming units (IFU), while the TaqMan test could detect 2 IFU. The amplicons produced in these tests ranged from 132 to 320 bp in length. The third test, targeting the 23S rRNA gene, produced a 600-bp amplicon from strains belonging to several families in the order Chlamydiales. Direct sequence analysis of this amplicon has facilitated the identification of new chlamydial strains. These three tests permit ready identification of chlamydiae for diagnostic and epidemiologic study. The specificity of these tests indicates that they might also be used to identify chlamydiae without culture or isolation. PMID:9986815

Creating fair lineups for suspects with distinctive features.

PubMed

Zarkadi, Theodora; Wade, Kimberley A; Stewart, Neil

2009-12-01

In their descriptions, eyewitnesses often refer to a culprit's distinctive facial features. However, in a police lineup, selecting the only member with the described distinctive feature is unfair to the suspect and provides the police with little further information. For fair and informative lineups, the distinctive feature should be either replicated across foils or concealed on the target. In the present experiments, replication produced more correct identifications in target-present lineups--without increasing the incorrect identification of foils in target-absent lineups--than did concealment. This pattern, and only this pattern, is predicted by the hybrid-similarity model of recognition.

Concrete Crack Identification Using a UAV Incorporating Hybrid Image Processing.

PubMed

Kim, Hyunjun; Lee, Junhwa; Ahn, Eunjong; Cho, Soojin; Shin, Myoungsu; Sim, Sung-Han

2017-09-07

Crack assessment is an essential process in the maintenance of concrete structures. In general, concrete cracks are inspected by manual visual observation of the surface, which is intrinsically subjective as it depends on the experience of inspectors. Further, it is time-consuming, expensive, and often unsafe when inaccessible structural members are to be assessed. Unmanned aerial vehicle (UAV) technologies combined with digital image processing have recently been applied to crack assessment to overcome the drawbacks of manual visual inspection. However, identification of crack information in terms of width and length has not been fully explored in the UAV-based applications, because of the absence of distance measurement and tailored image processing. This paper presents a crack identification strategy that combines hybrid image processing with UAV technology. Equipped with a camera, an ultrasonic displacement sensor, and a WiFi module, the system provides the image of cracks and the associated working distance from a target structure on demand. The obtained information is subsequently processed by hybrid image binarization to estimate the crack width accurately while minimizing the loss of the crack length information. The proposed system has shown to successfully measure cracks thicker than 0.1 mm with the maximum length estimation error of 7.3%.

Identification of individualised empirical models of carbohydrate and insulin effects on T1DM blood glucose dynamics

NASA Astrophysics Data System (ADS)

Cescon, Marzia; Johansson, Rolf; Renard, Eric; Maran, Alberto

2014-07-01

One of the main limiting factors in improving glucose control for type 1 diabetes mellitus (T1DM) subjects is the lack of a precise description of meal and insulin intake effects on blood glucose. Knowing the magnitude and duration of such effects would be useful not only for patients and physicians, but also for the development of a controller targeting glycaemia regulation. Therefore, in this paper we focus on estimating low-complexity yet physiologically sound and individualised multi-input single-output (MISO) models of the glucose metabolism in T1DM able to reflect the basic dynamical features of the glucose-insulin metabolic system in response to a meal intake or an insulin injection. The models are continuous-time second-order transfer functions relating the amount of carbohydrate of a meal and the insulin units of the accordingly administered dose (inputs) to plasma glucose evolution (output) and consist of few parameters clinically relevant to be estimated. The estimation strategy is continuous-time data-driven system identification and exploits a database in which meals and insulin boluses are separated in time, allowing the unique identification of the model parameters.

Purification of Encephalitozoon Cultures Contaminated by Mycoplasmas by Murine Intraperitoneal Inoculation

PubMed Central

Ridoux, Olivier; Foucault, Cédric; Drancourt, Michel

1998-01-01

Encephalitozoon species are strict intracellular microsporidia. Cocultures with eukaryotic cell lines can become accidently contaminated by mycoplasmas. We propose a decontamination protocol based on differential cell targeting after intraperitoneal inoculation in mice. Mycoplasma-free microsporidia were isolated from the brains and spleens of inoculated mice 24 h postinoculation by using the centrifugation shell vial system. Identification was confirmed by direct sequencing of PCR-amplified 16S rRNA. PMID:9666031

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

PubMed

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

2008-09-06

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.

Attention capture without awareness in a non-spatial selection task.

PubMed

Oriet, Chris; Pandey, Mamata; Kawahara, Jun-Ichiro

2017-02-01

Distractors presented prior to a critical target in a rapid sequence of visually-presented items induce a lag-dependent deficit in target identification, particularly when the distractor shares a task-relevant feature of the target. Presumably, such capture of central attention is important for bringing a target into awareness. The results of the present investigation suggest that greater capture of attention by a distractor is not accompanied by greater awareness of it. Moreover, awareness tends to be limited to superficial characteristics of the target such as colour. The findings are interpreted within the context of a model that assumes sudden increases in arousal trigger selection of information for consolidation in working memory. In this conceptualization, prolonged analysis of distractor items sharing task-relevant features leads to larger target identification deficits (i.e., greater capture) but no increase in awareness. Copyright © 2016 Elsevier Inc. All rights reserved.

Identification of distant drug off-targets by direct superposition of binding pocket surfaces.

PubMed

Schumann, Marcel; Armen, Roger S

2013-01-01

Correctly predicting off-targets for a given molecular structure, which would have the ability to bind a large range of ligands, is both particularly difficult and important if they share no significant sequence or fold similarity with the respective molecular target ("distant off-targets"). A novel approach for identification of off-targets by direct superposition of protein binding pocket surfaces is presented and applied to a set of well-studied and highly relevant drug targets, including representative kinases and nuclear hormone receptors. The entire Protein Data Bank is searched for similar binding pockets and convincing distant off-target candidates were identified that share no significant sequence or fold similarity with the respective target structure. These putative target off-target pairs are further supported by the existence of compounds that bind strongly to both with high topological similarity, and in some cases, literature examples of individual compounds that bind to both. Also, our results clearly show that it is possible for binding pockets to exhibit a striking surface similarity, while the respective off-target shares neither significant sequence nor significant fold similarity with the respective molecular target ("distant off-target").

iTAR: a web server for identifying target genes of transcription factors using ChIP-seq or ChIP-chip data.

PubMed

Yang, Chia-Chun; Andrews, Erik H; Chen, Min-Hsuan; Wang, Wan-Yu; Chen, Jeremy J W; Gerstein, Mark; Liu, Chun-Chi; Cheng, Chao

2016-08-12

Chromatin immunoprecipitation followed by massively parallel DNA sequencing (ChIP-seq) or microarray hybridization (ChIP-chip) has been widely used to determine the genomic occupation of transcription factors (TFs). We have previously developed a probabilistic method, called TIP (Target Identification from Profiles), to identify TF target genes using ChIP-seq/ChIP-chip data. To achieve high specificity, TIP applies a conservative method to estimate significance of target genes, with the trade-off being a relatively low sensitivity of target gene identification compared to other methods. Additionally, TIP's output does not render binding-peak locations or intensity, information highly useful for visualization and general experimental biological use, while the variability of ChIP-seq/ChIP-chip file formats has made input into TIP more difficult than desired. To improve upon these facets, here we present are fined TIP with key extensions. First, it implements a Gaussian mixture model for p-value estimation, increasing target gene identification sensitivity and more accurately capturing the shape of TF binding profile distributions. Second, it enables the incorporation of TF binding-peak data by identifying their locations in significant target gene promoter regions and quantifies their strengths. Finally, for full ease of implementation we have incorporated it into a web server ( http://syslab3.nchu.edu.tw/iTAR/ ) that enables flexibility of input file format, can be used across multiple species and genome assembly versions, and is freely available for public use. The web server additionally performs GO enrichment analysis for the identified target genes to reveal the potential function of the corresponding TF. The iTAR web server provides a user-friendly interface and supports target gene identification in seven species, ranging from yeast to human. To facilitate investigating the quality of ChIP-seq/ChIP-chip data, the web server generates the chart of the characteristic binding profiles and the density plot of normalized regulatory scores. The iTAR web server is a useful tool in identifying TF target genes from ChIP-seq/ChIP-chip data and discovering biological insights.

High-speed counter-current chromatography coupled online to high performance liquid chromatography-diode array detector-mass spectrometry for purification, analysis and identification of target compounds from natural products.

PubMed

Liang, Xuejuan; Zhang, Yuping; Chen, Wei; Cai, Ping; Zhang, Shuihan; Chen, Xiaoqin; Shi, Shuyun

2015-03-13

A challenge in coupling high-speed counter-current chromatography (HSCCC) online with high performance liquid chromatography (HPLC) for purity analysis was their time incompatibility. Consequently, HSCCC-HPLC was conducted by either controlling HPLC analysis time and HSCCC flow rate or using stop-and-go scheme. For natural products containing compounds with a wide range of polarities, the former would optimize experimental conditions, while the latter required more time. Here, a novel HSCCC-HPLC-diode array detector-mass spectrometry (HSCCC-HPLC-DAD-MS) was developed for undisrupted purification, analysis and identification of multi-compounds from natural products. Two six-port injection valves and a six-port switching valve were used as interface for collecting key HSCCC effluents alternatively for HPLC-DAD-MS analysis and identification. The ethyl acetate extract of Malus doumeri was performed on the hyphenated system to verify its efficacy. Five main flavonoids, 3-hydroxyphloridzin (1), phloridzin (2), 4',6'-dihydroxyhydrochalcone-2'-O-β-D-glucopyranoside (3, first found in M. doumeri), phloretin (4), and chrysin (5), were purified with purities over 99% by extrusion elution and/or stepwise elution mode in two-step HSCCC, and 25mM ammonium acetate solution was selected instead of water to depress emulsification in the first HSCCC. The online system shortened manipulation time largely compared with off-line analysis procedure and stop-and-go scheme. The results indicated that the present method could serve as a simple, rapid and effective way to achieve target compounds with high purity from natural products. Copyright © 2015 Elsevier B.V. All rights reserved.

Identification of GPCR-Interacting Cytosolic Proteins Using HDL Particles and Mass Spectrometry-Based Proteomic Approach

PubMed Central

Chung, Ka Young; Day, Peter W.; Vélez-Ruiz, Gisselle; Sunahara, Roger K.; Kobilka, Brian K.

2013-01-01

G protein-coupled receptors (GPCRs) have critical roles in various physiological and pathophysiological processes, and more than 40% of marketed drugs target GPCRs. Although the canonical downstream target of an agonist-activated GPCR is a G protein heterotrimer; there is a growing body of evidence suggesting that other signaling molecules interact, directly or indirectly, with GPCRs. However, due to the low abundance in the intact cell system and poor solubility of GPCRs, identification of these GPCR-interacting molecules remains challenging. Here, we establish a strategy to overcome these difficulties by using high-density lipoprotein (HDL) particles. We used the β2-adrenergic receptor (β2AR), a GPCR involved in regulating cardiovascular physiology, as a model system. We reconstituted purified β2AR in HDL particles, to mimic the plasma membrane environment, and used the reconstituted receptor as bait to pull-down binding partners from rat heart cytosol. A total of 293 proteins were identified in the full agonist-activated β2AR pull-down, 242 proteins in the inverse agonist-activated β2AR pull-down, and 210 proteins were commonly identified in both pull-downs. A small subset of the β2AR-interacting proteins isolated was confirmed by Western blot; three known β2AR-interacting proteins (Gsα, NHERF-2, and Grb2) and 3 newly identified known β2AR-interacting proteins (AMPKα, acetyl-CoA carboxylase, and UBC-13). Profiling of the identified proteins showed a clear bias toward intracellular signal transduction pathways, which is consistent with the role of β2AR as a cell signaling molecule. This study suggests that HDL particle-reconstituted GPCRs can provide an effective platform method for the identification of GPCR binding partners coupled with a mass spectrometry-based proteomic analysis. PMID:23372797

Optical Remote Sensing for Fence-Line Monitoring using Open-Path Quantum Cascade Laser (QCL) mono-static system for multiple target compounds in the Mid IR 7-13um (Fingerprint) region.

NASA Astrophysics Data System (ADS)

Zemek, P. G.

2017-12-01

Quantum Cascade Lasers (QCLs) are quickly replacing Tunable Diode Lasers (TDL) for multi-target species identification and quantification in both extractive and open-path (OP) Optical Remote Sensing (ORS) fence-line instrumentation. As was seen with TDL incorporation and pricing drops as the adoption by the telecommunications industry and its current scaling has improved robustness and pricing, the QCL is also, albiet more slowly, becoming a mature market. There are several advantages of QCLs over conventional TDLs such as improved brightness and beam density, high resolution, as well as the incorporation of external etalons or internal gratings to scan over wide spectral areas. QCLs typically operate in the Mid infra-red (MIR) as opposed to the Near-Infrared (NIR) region used with TDL. The MidIR is a target rich absorption band area where compounds have high absorbtivity coefficients resulting in better detection limits as compared to TDL instruments. The use of novel chemometrics and more sensitive non-cryo-cooled detectors has allowed some of the first QCL open-path instruments in both active and passive operation. Data and field studies of one of the newest QCL OP systems is presented that allows one system to measure multiple target compounds. Multiple QCL spectral regions may be stitched together to increase the capability of QCLs over TDL OP systems. A comparison of several ORS type systems will be presented.

The influence of incubation time, sample preparation and exposure to oxygen on the quality of the MALDI-TOF MS spectrum of anaerobic bacteria.

PubMed

Veloo, A C M; Elgersma, P E; Friedrich, A W; Nagy, E; van Winkelhoff, A J

2014-12-01

With matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS), bacteria can be identified quickly and reliably. This accounts especially for anaerobic bacteria. Because growth rate and oxygen sensitivity differ among anaerobic bacteria, we aimed to study the influence of incubation time, exposure to oxygen and sample preparation on the quality of the spectrum using the Bruker system. Also, reproducibility and inter-examiner variability were determined. Twenty-six anaerobic species, representing 17 genera, were selected based on gram-stain characteristics, growth rate and colony morphology. Inter-examiner variation showed that experience in the preparation of the targets can be a significant variable. The influence of incubation time was determined between 24 and 96 h of incubation. Reliable species identification was obtained after 48 h of incubation for gram-negative anaerobes and after 72 h for gram-positive anaerobes. Exposure of the cultures to oxygen did not influence the results of the MALDI-TOF MS identifications of all tested gram-positive species. Fusobacterium necrophorum and Prevotella intermedia could not be identified after >24 h and 48 h of exposure to oxygen, respectively. Other tested gram-negative bacteria could be identified after 48 h of exposure to oxygen. Most of the tested species could be identified using the direct spotting method. Bifidobacterium longum and Finegoldia magna needed on-target extraction with 70% formic acid in order to obtain reliable species identification and Peptoniphilus ivorii a full extraction. Spectrum quality was influenced by the amount of bacteria spotted on the target, the homogeneity of the smear and the experience of the examiner. © 2014 The Authors Clinical Microbiology and Infection © 2014 European Society of Clinical Microbiology and Infectious Diseases.

In-depth 2-DE reference map of Aspergillus fumigatus and its proteomic profiling on exposure to itraconazole.

PubMed

Gautam, Poonam; Mushahary, Dolly; Hassan, Wazid; Upadhyay, Santosh Kumar; Madan, Taruna; Sirdeshmukh, Ravi; Sundaram, Curam Sreenivasacharlu; Sarma, Puranam Usha

2016-07-01

Aspergillus fumigatus (A. fumigatus) is a medically important opportunistic fungus that may lead to invasive aspergillosis in humans with weak immune system. Proteomic profiling of this fungus on exposure to itraconazole (ITC), an azole antifungal drug, may lead to identification of its molecular targets and better understanding on the development of drug resistance against ITC in A. fumigatus. Here, proteome analysis was performed using 2-DE followed by mass spectrometric analysis which resulted in identification of a total of 259 unique proteins. Further, proteome profiling of A. fumigatus was carried out on exposure to ITC, 0.154 μg/ml, the minimum inhibitory concentration (MIC50). Image analysis showed altered levels of 175 proteins (66 upregulated and 109 downregulated) of A. fumigatus treated with ITC as compared to the untreated control. Peptide mass fingerprinting led to the identification of 54 proteins (12 up-regulated and 42 down-regulated). The differentially expressed proteins include proteins related to cell stress, carbohydrate metabolism and amino acid metabolism. We also observed four proteins, including nucleotide phosphate kinase (NDK), that are reported to interact with calcineurin, a protein involved in regulation of cell morphology and fungal virulence. Comparison of differentially expressed proteins on exposure to ITC with artemisinin (ART), an antimalarial drug with antifungal activity(1), revealed a total of 26 proteins to be common among them suggesting that common proteins and pathways are targeted by these two antifungal agents. The proteins targeted by ITC may serve as important leads for development of new antifungal drugs. © The Author 2016. Published by Oxford University Press on behalf of The International Society for Human and Animal Mycology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

Design of tracking and detecting lens system by diffractive optical method

NASA Astrophysics Data System (ADS)

Yang, Jiang; Qi, Bo; Ren, Ge; Zhou, Jianwei

2016-10-01

Many target-tracking applications require an optical system to acquire the target for tracking and identification. This paper describes a new detecting optical system that can provide automatic flying object detecting, tracking and measuring in visible band. The main feature of the detecting lens system is the combination of diffractive optics with traditional lens design by a technique was invented by Schupmann. Diffractive lens has great potential for developing the larger aperture and lightweight lens. First, the optical system scheme was described. Then the Schupmann achromatic principle with diffractive lens and corrective optics is introduced. According to the technical features and requirements of the optical imaging system for detecting and tracking, we designed a lens system with flat surface Fresnel lens and cancels the optical system chromatic aberration by another flat surface Fresnel lens with effective focal length of 1980mm, an F-Number of F/9.9 and a field of view of 2ωω = 14.2', spatial resolution of 46 lp/mm and a working wavelength range of 0.6 0.85um. At last, the system is compact and easy to fabricate and assembly, the diffuse spot size and MTF function and other analysis provide good performance.

Identification of polycystic ovary syndrome potential drug targets based on pathobiological similarity in the protein-protein interaction network

PubMed Central

Li, Wan; Wei, Wenqing; Li, Yiran; Xie, Ruiqiang; Guo, Shanshan; Wang, Yahui; Jiang, Jing; Chen, Binbin; Lv, Junjie; Zhang, Nana; Chen, Lina; He, Weiming

2016-01-01

Polycystic ovary syndrome (PCOS) is one of the most common endocrinological disorders in reproductive aged women. PCOS and Type 2 Diabetes (T2D) are closely linked in multiple levels and possess high pathobiological similarity. Here, we put forward a new computational approach based on the pathobiological similarity to identify PCOS potential drug target modules (PPDT-Modules) and PCOS potential drug targets in the protein-protein interaction network (PPIN). From the systems level and biological background, 1 PPDT-Module and 22 PCOS potential drug targets were identified, 21 of which were verified by literatures to be associated with the pathogenesis of PCOS. 42 drugs targeting to 13 PCOS potential drug targets were investigated experimentally or clinically for PCOS. Evaluated by independent datasets, the whole PPDT-Module and 22 PCOS potential drug targets could not only reveal the drug response, but also distinguish the statuses between normal and disease. Our identified PPDT-Module and PCOS potential drug targets would shed light on the treatment of PCOS. And our approach would provide valuable insights to research on the pathogenesis and drug response of other diseases. PMID:27191267

Camera calibration: active versus passive targets

NASA Astrophysics Data System (ADS)

Schmalz, Christoph; Forster, Frank; Angelopoulou, Elli

2011-11-01

Traditionally, most camera calibrations rely on a planar target with well-known marks. However, the localization error of the marks in the image is a source of inaccuracy. We propose the use of high-resolution digital displays as active calibration targets to obtain more accurate calibration results for all types of cameras. The display shows a series of coded patterns to generate correspondences between world points and image points. This has several advantages. No special calibration hardware is necessary because suitable displays are practically ubiquitious. The method is fully automatic, and no identification of marks is necessary. For a coding scheme based on phase shifting, the localization accuracy is approximately independent of the camera's focus settings. Most importantly, higher accuracy can be achieved compared to passive targets, such as printed checkerboards. A rigorous evaluation is performed to substantiate this claim. Our active target method is compared to standard calibrations using a checkerboard target. We perform camera, calibrations with different combinations of displays, cameras, and lenses, as well as with simulated images and find markedly lower reprojection errors when using active targets. For example, in a stereo reconstruction task, the accuracy of a system calibrated with an active target is five times better.

Performance of resonant radar target identification algorithms using intra-class weighting functions

NASA Astrophysics Data System (ADS)

Mustafa, A.

The use of calibrated resonant-region radar cross section (RCS) measurements of targets for the classification of large aircraft is discussed. Errors in the RCS estimate of full scale aircraft flying over an ocean, introduced by the ionospheric variability and the sea conditions were studied. The Weighted Target Representative (WTR) classification algorithm was developed, implemented, tested and compared with the nearest neighbor (NN) algorithm. The WTR-algorithm has a low sensitivity to the uncertainty in the aspect angle of the unknown target returns. In addition, this algorithm was based on the development of a new catalog of representative data which reduces the storage requirements and increases the computational efficiency of the classification system compared to the NN-algorithm. Experiments were designed to study and evaluate the characteristics of the WTR- and the NN-algorithms, investigate the classifiability of targets and study the relative behavior of the number of misclassifications as a function of the target backscatter features. The classification results and statistics were shown in the form of performance curves, performance tables and confusion tables.

Identification of targets for rational pharmacological therapy in childhood craniopharyngioma.

PubMed

Gump, Jacob M; Donson, Andrew M; Birks, Diane K; Amani, Vladimir M; Rao, Karun K; Griesinger, Andrea M; Kleinschmidt-DeMasters, B K; Johnston, James M; Anderson, Richard C E; Rosenfeld, Amy; Handler, Michael; Gore, Lia; Foreman, Nicholas; Hankinson, Todd C

2015-05-21

Pediatric adamantinomatous craniopharyngioma (ACP) is a histologically benign but clinically aggressive brain tumor that arises from the sellar/suprasellar region. Despite a high survival rate with current surgical and radiation therapy (75-95 % at 10 years), ACP is associated with debilitating visual, endocrine, neurocognitive and psychological morbidity, resulting in excheptionally poor quality of life for survivors. Identification of an effective pharmacological therapy could drastically decrease morbidity and improve long term outcomes for children with ACP. Using mRNA microarray gene expression analysis of 15 ACP patient samples, we have found several pharmaceutical targets that are significantly and consistently overexpressed in our panel of ACP relative to other pediatric brain tumors, pituitary tumors, normal pituitary and normal brain tissue. Among the most highly expressed are several targets of the kinase inhibitor dasatinib - LCK, EPHA2 and SRC; EGFR pathway targets - AREG, EGFR and ERBB3; and other potentially actionable cancer targets - SHH, MMP9 and MMP12. We confirm by western blot that a subset of these targets is highly expressed in ACP primary tumor samples. We report here the first published transcriptome for ACP and the identification of targets for rational therapy. Experimental drugs targeting each of these gene products are currently being tested clinically and pre-clinically for the treatment of other tumor types. This study provides a rationale for further pre-clinical and clinical studies of novel pharmacological treatments for ACP. Development of mouse and cell culture models for ACP will further enable the translation of these targets from the lab to the clinic, potentially ushering in a new era in the treatment of ACP.

Probability of identification (POI): a statistical model for the validation of qualitative botanical identification methods

USDA-ARS?s Scientific Manuscript database

A qualitative botanical identification method (BIM) is an analytical procedure which returns a binary result (1 = Identified, 0 = Not Identified). A BIM may be used by a buyer, manufacturer, or regulator to determine whether a botanical material being tested is the same as the target (desired) mate...

Device for detection and identification of carbon- and nitrogen-containing materials

DOEpatents

Karev, Alexander Ivanovich; Raevsky, Valery Georgievich; Dzhilavyan, Leonid Zavenovich; Laptev, Valery Dmitrievich; Pakhomov, Nikolay Ivanovich; Shvedunov, Vasily Ivanovich; Rykalin, Vladimir Ivanovich; Brothers, Louis Joseph; Wilhide, Larry K

2014-03-25

A device for detection and identification of carbon- and nitrogen-containing materials is described. In particular, the device performs the detection and identification of carbon- and nitrogen-containing materials by photo-nuclear detection. The device may comprise a race-track microtron, a breaking target, and a water-filled Cherenkov radiation counter.

A nonlinear disturbance-decoupled elevation axis controller for the Multiple Mirror Telescope

NASA Astrophysics Data System (ADS)

Clark, Dusty; Trebisky, Tom; Powell, Keith

2008-07-01

The Multiple Mirror Telescope (MMT), upgraded in 2000 to a monolithic 6.5m primary mirror from its original array of six 1.8m primary mirrors, was commissioned with axis controllers designed early in the upgrade process without regard to structural resonances or the possibility of the need for digital filtering of the control axis signal path. Post-commissioning performance issues led us to investigate replacement of the original control system with a more modern digital controller with full control over the system filters and gain paths. This work, from system identification through controller design iteration by simulation, and pre-deployment hardware-in-the-loop testing, was performed using latest-generation tools with Matlab® and Simulink®. Using Simulink's Real Time Workshop toolbox to automatically generate C source code for the controller from the Simulink diagram and a custom target build script, we were able to deploy the new controller into our existing software infrastructure running Wind River's VxWorks™real-time operating system. This paper describes the process of the controller design, including system identification data collection, with discussion of implementation of non-linear control modes and disturbance decoupling, which became necessary to obtain acceptable wind buffeting rejection.

Mass spectrometry techniques for studying the ubiquitin system.

PubMed

Heap, Rachel E; Gant, Megan S; Lamoliatte, Frederic; Peltier, Julien; Trost, Matthias

2017-10-15

Post-translational control of proteins through covalent attachment of ubiquitin plays important roles in all eukaryotic cell functions. The ubiquitin system in humans consists of 2 E1, 35 E2 and >600 E3 ubiquitin ligases as well as hundreds of deubiquitylases, which reverse ubiquitin attachment. Moreover, there are hundreds of proteins with ubiquitin-binding domains that bind one of the eight possible polyubiquitin chains. Dysfunction of the ubiquitin system is associated with many diseases such as cancer, autoimmunity and neurodegeneration, demonstrating the importance of ubiquitylation. Therefore, enzymes of the ubiquitin system are considered highly attractive drug targets. In recent years, mass spectrometry (MS)-based techniques have become increasingly important in the deciphering of the ubiquitin system. This short review addresses the state-of-the-art MS techniques for the identification of ubiquitylated proteins and their ubiquitylation sites. We also discuss the identification and quantitation of ubiquitin chain topologies and highlight how the activity of enzymes in the ubiquitin pathway can be measured. Finally, we present current MS tools that can be used for drug discovery in the ubiquitin space. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

The status of the art of human malignant glioma management: the promising role of targeting tumor-initiating cells.

PubMed

Florio, Tullio; Barbieri, Federica

2012-10-01

Glioblastoma is the most prevalent and malignant form of brain cancer, but the current available multimodality treatments yield poor survival improvement. Thus, innovative therapeutic strategies represent the challenging topic for glioblastoma management. Multidisciplinary advances, supporting current standard of care therapies and investigational trials that reveal potential drug targets for glioblastoma are reviewed. A radical change in glioblastoma therapeutic approaches could arise from the identification of cancer stem cells, putative tumor-initiating cells involved in tumor initiation, progression and resistance, as innovative drug target. Still controversial identification of markers and molecular regulators in glioma tumor-initiating cells and novel approaches targeting these cells are discussed. Copyright © 2012 Elsevier Ltd. All rights reserved.

Comparison of internal transcribed spacers and intergenic spacer regions of five common Iranian sheep bursate nematodes.

PubMed

Nabavi, Reza; Conneely, Brendan; McCarthy, Elaine; Good, Barbara; Shayan, Parviz; DE Waal, Theo

2014-09-01

Accurate identification of sheep nematodes is a critical point in epidemiological studies and monitoring of drug resistance in flocks. However, due to a close morphological similarity between the eggs and larval stages of many of these nematodes, such identification is not a trivial task. There are a number of studies showing that molecular targets in ribosomal DNA (Internal transcribed spacer 1, 2 and Intergenic spacer) are suitable for accurate identification of sheep bursate nematodes. The objective of present study was to compare the ITS1, ITS2 and IGS regions of Iranian common bursate nematodes in order to choose best target for specific identification methods. The first and second internal transcribed spacers (ITS1and ITS2) and intergenic spacer (IGS) of the ribosomal DNA (rDNA) of 5 common Iranian bursate nematodes of sheep were sequenced. The sequences of some non-Iranian isolates were used for comparison in order to evaluate the variation in sequence homology between geographically different nematode populations. Comparison of the ITS1 and ITS2 sequences of Iranian nematodes showed greatest similarity among Teladorsagia circumcincta and Marshallagia marshalli of 94% and 88%, respectively. While Trichostrongylus colubriformis and M. marshalli showed the highest homology (99%) in the IGS sequences. Comparison of the spacer sequences of Iranian with non-Iranian isolates showed significantly higher variation in Haemonchus contortus compared to the other species. Both the ITS1 and ITS2 sequences are convenient targets to have species-specific identification of Iranian bursate nematodes. On the other hand the IGS region may be a less suitable molecular target.

An integrated miRNA functional screening and target validation method for organ morphogenesis.

PubMed

Rebustini, Ivan T; Vlahos, Maryann; Packer, Trevor; Kukuruzinska, Maria A; Maas, Richard L

2016-03-16

The relative ease of identifying microRNAs and their increasing recognition as important regulators of organogenesis motivate the development of methods to efficiently assess microRNA function during organ morphogenesis. In this context, embryonic organ explants provide a reliable and reproducible system that recapitulates some of the important early morphogenetic processes during organ development. Here we present a method to target microRNA function in explanted mouse embryonic organs. Our method combines the use of peptide-based nanoparticles to transfect specific microRNA inhibitors or activators into embryonic organ explants, with a microRNA pulldown assay that allows direct identification of microRNA targets. This method provides effective assessment of microRNA function during organ morphogenesis, allows prioritization of multiple microRNAs in parallel for subsequent genetic approaches, and can be applied to a variety of embryonic organs.

Towards Autonomous Modular UAV Missions: The Detection, Geo-Location and Landing Paradigm

PubMed Central

Kyristsis, Sarantis; Antonopoulos, Angelos; Chanialakis, Theofilos; Stefanakis, Emmanouel; Linardos, Christos; Tripolitsiotis, Achilles; Partsinevelos, Panagiotis

2016-01-01

Nowadays, various unmanned aerial vehicle (UAV) applications become increasingly demanding since they require real-time, autonomous and intelligent functions. Towards this end, in the present study, a fully autonomous UAV scenario is implemented, including the tasks of area scanning, target recognition, geo-location, monitoring, following and finally landing on a high speed moving platform. The underlying methodology includes AprilTag target identification through Graphics Processing Unit (GPU) parallelized processing, image processing and several optimized locations and approach algorithms employing gimbal movement, Global Navigation Satellite System (GNSS) readings and UAV navigation. For the experimentation, a commercial and a custom made quad-copter prototype were used, portraying a high and a low-computational embedded platform alternative. Among the successful targeting and follow procedures, it is shown that the landing approach can be successfully performed even under high platform speeds. PMID:27827883

Towards Autonomous Modular UAV Missions: The Detection, Geo-Location and Landing Paradigm.

PubMed

Kyristsis, Sarantis; Antonopoulos, Angelos; Chanialakis, Theofilos; Stefanakis, Emmanouel; Linardos, Christos; Tripolitsiotis, Achilles; Partsinevelos, Panagiotis

2016-11-03

Nowadays, various unmanned aerial vehicle (UAV) applications become increasingly demanding since they require real-time, autonomous and intelligent functions. Towards this end, in the present study, a fully autonomous UAV scenario is implemented, including the tasks of area scanning, target recognition, geo-location, monitoring, following and finally landing on a high speed moving platform. The underlying methodology includes AprilTag target identification through Graphics Processing Unit (GPU) parallelized processing, image processing and several optimized locations and approach algorithms employing gimbal movement, Global Navigation Satellite System (GNSS) readings and UAV navigation. For the experimentation, a commercial and a custom made quad-copter prototype were used, portraying a high and a low-computational embedded platform alternative. Among the successful targeting and follow procedures, it is shown that the landing approach can be successfully performed even under high platform speeds.

New chemical probe technologies: applications to imaging and drug discovery (Conference Presentation)

NASA Astrophysics Data System (ADS)

Bogyo, Matthew

2017-02-01

Proteases are enzymes that play pathogenic roles in many common human diseases such as cancer, asthma, arthritis, atherosclerosis and infection by pathogens. Tools to dynamically monitor their activity can be used as diagnostic agents, as imaging contrast agents for intra-operative image guidance and for the identification of novel classes of protease-targeted drugs. I will describe our efforts to design and synthesize small molecule probes that produce a fluorescent signal upon binding to a protease target. We have identified probes that show tumor-specific retention, fast activation kinetics, and rapid systemic distribution making them useful for real-time fluorescence guided tumor resection and other diagnostic imaging applications.

Objective, Quantitative, Data-Driven Assessment of Chemical Probes.

PubMed

Antolin, Albert A; Tym, Joseph E; Komianou, Angeliki; Collins, Ian; Workman, Paul; Al-Lazikani, Bissan

2018-02-15

Chemical probes are essential tools for understanding biological systems and for target validation, yet selecting probes for biomedical research is rarely based on objective assessment of all potential compounds. Here, we describe the Probe Miner: Chemical Probes Objective Assessment resource, capitalizing on the plethora of public medicinal chemistry data to empower quantitative, objective, data-driven evaluation of chemical probes. We assess >1.8 million compounds for their suitability as chemical tools against 2,220 human targets and dissect the biases and limitations encountered. Probe Miner represents a valuable resource to aid the identification of potential chemical probes, particularly when used alongside expert curation. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

What good is SWIR? Passive day comparison of VIS, NIR, and SWIR

NASA Astrophysics Data System (ADS)

Driggers, Ronald G.; Hodgkin, Van; Vollmerhausen, Richard

2013-06-01

This paper is the first of three papers associated with the military benefits of SWIR imaging. This paper describes the benefits associated with passive daytime operations with comparisons of SWIR, NIR, and VIS bands and sensors. This paper includes quantitative findings from previously published papers, analysis of open source data, summaries of various expert analyses, and calculations of notional system performance. We did not accept anecdotal findings as acceptable benefits. Topics include haze and fog penetration, atmospheric transmission, cloud and smoke penetration, target and background contrasts, spectral discrimination, turbulence degradation, and long range target identification. The second and third papers will address passive night imaging and active night imaging.