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.

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.

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.

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.

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.

Uridine monophosphate kinase as potential target for tuberculosis: from target to lead identification.

PubMed

Arvind, Akanksha; Jain, Vaibhav; Saravanan, Parameswaran; Mohan, C Gopi

2013-12-01

Mycobacterium tuberculosis (Mtb) is a causative agent of tuberculosis (TB) disease, which has affected approximately 2 billion people worldwide. Due to the emergence of resistance towards the existing drugs, discovery of new anti-TB drugs is an important global healthcare challenge. To address this problem, there is an urgent need to identify new drug targets in Mtb. In the present study, the subtractive genomics approach has been employed for the identification of new drug targets against TB. Screening the Mtb proteome using the Database of Essential Genes (DEG) and human proteome resulted in the identification of 60 key proteins which have no eukaryotic counterparts. Critical analysis of these proteins using Kyoto Encyclopedia of Genes and Genomes (KEGG) metabolic pathways database revealed uridine monophosphate kinase (UMPK) enzyme as a potential drug target for developing novel anti-TB drugs. Homology model of Mtb-UMPK was constructed for the first time on the basis of the crystal structure of E. coli-UMPK, in order to understand its structure-function relationships, and which would in turn facilitate to perform structure-based inhibitor design. Furthermore, the structural similarity search was carried out using physiological inhibitor UTP of Mtb-UMPK to virtually screen ZINC database. Retrieved hits were further screened by implementing several filters like ADME and toxicity followed by molecular docking. Finally, on the basis of the Glide docking score and the mode of binding, 6 putative leads were identified as inhibitors of this enzyme which can potentially emerge as future drugs for the treatment of TB.

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

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.

Modeling of video compression effects on target acquisition performance

NASA Astrophysics Data System (ADS)

Cha, Jae H.; Preece, Bradley; Espinola, Richard L.

2009-05-01

The effect of video compression on image quality was investigated from the perspective of target acquisition performance modeling. Human perception tests were conducted recently at the U.S. Army RDECOM CERDEC NVESD, measuring identification (ID) performance on simulated military vehicle targets at various ranges. These videos were compressed with different quality and/or quantization levels utilizing motion JPEG, motion JPEG2000, and MPEG-4 encoding. To model the degradation on task performance, the loss in image quality is fit to an equivalent Gaussian MTF scaled by the Structural Similarity Image Metric (SSIM). Residual compression artifacts are treated as 3-D spatio-temporal noise. This 3-D noise is found by taking the difference of the uncompressed frame, with the estimated equivalent blur applied, and the corresponding compressed frame. Results show good agreement between the experimental data and the model prediction. This method has led to a predictive performance model for video compression by correlating various compression levels to particular blur and noise input parameters for NVESD target acquisition performance model suite.

The verbal facilitation effect: re-reading person descriptions as a system variable to improve identification performance.

PubMed

Sporer, Siegfried L; Kaminski, Kristina S; Davids, Maike C; McQuiston, Dawn

2016-11-01

When witnesses report a crime, police usually ask for a description of the perpetrator. Several studies suggested that verbalising faces leads to a detriment in identification performance (verbal overshadowing effect [VOE]) but the effect has been difficult to replicate. Here, we sought to reverse the VOE by inducing context reinstatement as a system variable through re-reading one's own description before an identification task. Participants (N = 208) watched a video film and were then dismissed (control group), only described the perpetrator, or described and later re-read their own descriptions before identification in either target-present or target-absent lineups after a 2-day or a 5-week delay. Identification accuracy was significantly higher after re-reading (85.0%) than in the no description control group (62.5%) irrespective of target presence. Data were internally replicated using a second target and corroborated by several small meta-analyses. Identification accuracy was related to description quality. Moreover, there was a tendency towards a verbal facilitation effect (VFE) rather than a VOE. Receiver operating characteristic (ROC) curve analyses confirm that our findings are not due to a shift in response bias but truly reflect improvement of recognition performance. Differences in the ecological validity of study paradigms are discussed.

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 mi

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

Replicating distinctive facial features in lineups: identification performance in young versus older adults.

PubMed

Badham, Stephen P; Wade, Kimberley A; Watts, Hannah J E; Woods, Natalie G; Maylor, Elizabeth A

2013-04-01

Criminal suspects with distinctive facial features, such as tattoos or bruising, may stand out in a police lineup. To prevent suspects from being unfairly identified on the basis of their distinctive feature, the police often manipulate lineup images to ensure that all of the members appear similar. Recent research shows that replicating a distinctive feature across lineup members enhances eyewitness identification performance, relative to removing that feature on the target. In line with this finding, the present study demonstrated that with young adults (n = 60; mean age = 20), replication resulted in more target identifications than did removal in target-present lineups and that replication did not impair performance, relative to removal, in target-absent lineups. Older adults (n = 90; mean age = 74) performed significantly worse than young adults, identifying fewer targets and more foils; moreover, older adults showed a minimal benefit from replication over removal. This pattern is consistent with the associative deficit hypothesis of aging, such that older adults form weaker links between faces and their distinctive features. Although replication did not produce much benefit over removal for older adults, it was not detrimental to their performance. Therefore, the results suggest that replication may not be as beneficial to older adults as it is to young adults and demonstrate a new practical implication of age-related associative deficits in memory.

Leveraging 3D chemical similarity, target and phenotypic data in the identification of drug-protein and drug-adverse effect associations.

PubMed

Vilar, Santiago; Hripcsak, George

2016-01-01

Drug-target identification is crucial to discover novel applications for existing drugs and provide more insights about mechanisms of biological actions, such as adverse drug effects (ADEs). Computational methods along with the integration of current big data sources provide a useful framework for drug-target and drug-adverse effect discovery. In this article, we propose a method based on the integration of 3D chemical similarity, target and adverse effect data to generate a drug-target-adverse effect predictor along with a simple leveraging system to improve identification of drug-targets and drug-adverse effects. In the first step, we generated a system for multiple drug-target identification based on the application of 3D drug similarity into a large target dataset extracted from the ChEMBL. Next, we developed a target-adverse effect predictor combining targets from ChEMBL with phenotypic information provided by SIDER data source. Both modules were linked to generate a final predictor that establishes hypothesis about new drug-target-adverse effect candidates. Additionally, we showed that leveraging drug-target candidates with phenotypic data is very useful to improve the identification of drug-targets. The integration of phenotypic data into drug-target candidates yielded up to twofold precision improvement. In the opposite direction, leveraging drug-phenotype candidates with target data also yielded a significant enhancement in the performance. The modeling described in the current study is simple and efficient and has applications at large scale in drug repurposing and drug safety through the identification of mechanism of action of biological effects.

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

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.

Target detection cycle criteria when using the targeting task performance metric

NASA Astrophysics Data System (ADS)

Hixson, Jonathan G.; Jacobs, Eddie L.; Vollmerhausen, Richard H.

2004-12-01

The US Army RDECOM CERDEC Night Vision and Electronic Sensors Directorate of the US Army (NVESD) has developed a new target acquisition metric to better predict the performance of modern electro-optical imagers. The TTP metric replaces the Johnson criteria. One problem with transitioning to the new model is that the difficulty of searching in a terrain has traditionally been quantified by an "N50." The N50 is the number of Johnson criteria cycles needed for the observer to detect the target half the time, assuming that the observer is not time limited. In order to make use of this empirical data base, a conversion must be found relating Johnson cycles for detection to TTP cycles for detection. This paper describes how that relationship is established. We have found that the relationship between Johnson and TTP is 1:2.7 for the recognition and identification tasks.

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.

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

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

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

PubMed

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

2017-06-01

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

RISC RNA sequencing for context-specific identification of in vivo miR targets

PubMed Central

Matkovich, Scot J; Van Booven, Derek J; Eschenbacher, William H; Dorn, Gerald W

2010-01-01

Rationale 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. Objective 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). Methods and Results 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 1,645 mRNAs consistently targeted to mouse cardiac RISCs. We employed 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. Conclusions 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. Summary MicroRNAs (miRs) are key regulators of mRNA translation in health and disease. While bioinformatic predictions suggest that a single miR may target hundreds of mRNAs, the number of experimentally verified targets of miRs is low. To enable comprehensive, unbiased examination of miR targets, we have performed deep RNA sequencing of cardiac transcriptomes in parallel with cardiac RNA-induced silencing complex

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.

[Exploring New Drug Targets through the Identification of Target Molecules of Bioactive Natural Products].

PubMed

Arai, Masayoshi

2016-01-01

With the development of cell biology and microbiology, it has become easy to culture many types of animal cells and microbes, and they are frequently used for phenotypic screening to explore medicinal seeds. On the other hand, it is recognized that cells and pathogenic microbes present in pathologic sites and infected regions of the human body display unique properties different from those under general culture conditions. We isolated several bioactive compounds from marine medicinal resources using constructed bioassay-guided separation focusing on the unique changes in the characteristics of cells and pathogenic microbes (Mycobacterium spp.) in the human body under disease conditions. In addition, we also carried out identification studies of target molecules of the bioactive compounds by methods utilizing the gene expression profile, transformants of cells or microbes, synthetic probe molecules of the isolated compounds, etc., since bioactive compounds isolated from the phenotypic screening system often target new molecules. This review presents our phenotypic screening systems, isolation of bioactive compounds from marine medicinal resources, and target identification of bioactive compounds.

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

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.

Identification of chemogenomic features from drug–target interaction networks using interpretable classifiers

PubMed Central

Tabei, Yasuo; Pauwels, Edouard; Stoven, Véronique; Takemoto, Kazuhiro; Yamanishi, Yoshihiro

2012-01-01

Motivation: Drug effects are mainly caused by the interactions between drug molecules and their target proteins including primary targets and off-targets. Identification of the molecular mechanisms behind overall drug–target interactions is crucial in the drug design process. Results: We develop a classifier-based approach to identify chemogenomic features (the underlying associations between drug chemical substructures and protein domains) that are involved in drug–target interaction networks. We propose a novel algorithm for extracting informative chemogenomic features by using L1 regularized classifiers over the tensor product space of possible drug–target pairs. It is shown that the proposed method can extract a very limited number of chemogenomic features without loosing the performance of predicting drug–target interactions and the extracted features are biologically meaningful. The extracted substructure–domain association network enables us to suggest ligand chemical fragments specific for each protein domain and ligand core substructures important for a wide range of protein families. Availability: Softwares are available at the supplemental website. Contact: yamanishi@bioreg.kyushu-u.ac.jp Supplementary Information: Datasets and all results are available at http://cbio.ensmp.fr/~yyamanishi/l1binary/ . PMID:22962471

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.

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

Targeted stock identification using multilocus genotype 'familyprinting'

USGS Publications Warehouse

Letcher, B.H.; King, T.L.

1999-01-01

We present an approach to stock identification of small, targeted populations that uses multilocus microsatellite genotypes of individual mating adults to uniquely identify first- and second-generation offspring in a mixture. We call the approach 'familyprinting'; unlike DNA fingerprinting where tissue samples of individuals are matched, offspring from various families are assigned to pairs of parents or sets of four grandparents with known genotypes. The basic unit of identification is the family, but families can be nested within a variety of stock units ranging from naturally reproducing groups of fish in a small tributary or pond from which mating adults can be sampled to large or small collections of families produced in hatcheries and stocked in specific locations. We show that, with as few as seven alleles per locus using four loci without error, first-generation offspring can be uniquely assigned to the correct family. For second-generation applications in a hatchery more alleles per locus (10) and loci (10) are required for correct assignment of all offspring to the correct set of grandparents. Using microsatellite DNA variation from an Atlantic salmon (Salmo solar) restoration river (Connecticut River, USA), we also show that this population contains sufficient genetic diversity in sea-run returns for 100% correct first, generation assignment and 97% correct second-generation assignment using 14 loci. We are currently using first- and second-generation familyprinting in this population with the ultimate goal of identifying stocking tributary. In addition to within-river familyprinting, there also appears to be sufficient genetic diversity within and between Atlantic salmon populations for identification of 'familyprinted' fish in a mixture of multiple populations. We also suggest that second-generation familyprinting with multiple populations may also provide a tool for examining stock structure. Familyprinting with microsatellite DNA markers is a viable

Target specific compound identification using a support vector machine.

PubMed

Plewczynski, Dariusz; von Grotthuss, Marcin; Spieser, Stephane A H; Rychlewski, Leszek; Wyrwicz, Lucjan S; Ginalski, Krzysztof; Koch, Uwe

2007-03-01

In many cases at the beginning of an HTS-campaign, some information about active molecules is already available. Often known active compounds (such as substrate analogues, natural products, inhibitors of a related protein or ligands published by a pharmaceutical company) are identified in low-throughput validation studies of the biochemical target. In this study we evaluate the effectiveness of a support vector machine applied for those compounds and used to classify a collection with unknown activity. This approach was aimed at reducing the number of compounds to be tested against the given target. Our method predicts the biological activity of chemical compounds based on only the atom pairs (AP) two dimensional topological descriptors. The supervised support vector machine (SVM) method herein is trained on compounds from the MDL drug data report (MDDR) known to be active for specific protein target. For detailed analysis, five different biological targets were selected including cyclooxygenase-2, dihydrofolate reductase, thrombin, HIV-reverse transcriptase and antagonists of the estrogen receptor. The accuracy of compound identification was estimated using the recall and precision values. The sensitivities for all protein targets exceeded 80% and the classification performance reached 100% for selected targets. In another application of the method, we addressed the absence of an initial set of active compounds for a selected protein target at the beginning of an HTS-campaign. In such a case, virtual high-throughput screening (vHTS) is usually applied by using a flexible docking procedure. However, the vHTS experiment typically contains a large percentage of false positives that should be verified by costly and time-consuming experimental follow-up assays. The subsequent use of our machine learning method was found to improve the speed (since the docking procedure was not required for all compounds from the database) and also the accuracy of the HTS hit lists (the

Performance characterization of material identification systems

NASA Astrophysics Data System (ADS)

Brown, Christopher D.; Green, Robert L.

2006-10-01

In recent years a number of analytical devices have been proposed and marketed specifically to enable field-based material identification. Technologies reliant on mass, near- and mid-infrared, and Raman spectroscopies are available today, and other platforms are imminent. These systems tend to perform material recognition based on an on-board library of material signatures. While figures of merit for traditional quantitative analytical sensors are broadly established (e.g., SNR, selectivity, sensitivity, limit of detection/decision), measures of performance for material identification systems have not been systematically discussed. In this paper we present an approach to performance characterization similar in spirit to ROC curves, but including elements of precision-recall curves and specialized for the intended-use of material identification systems. Important experimental considerations are discussed, including study design, sources of bias, uncertainty estimation, and cross-validation and the approach as a whole is illustrated using a commercially available handheld Raman material identification system.

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

PubMed

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

2017-05-31

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

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.

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.

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.

RNAi screen for rapid therapeutic target identification in leukemia patients

PubMed Central

Tyner, Jeffrey W.; Deininger, Michael W.; Loriaux, Marc M.; Chang, Bill H.; Gotlib, Jason R.; Willis, Stephanie G.; Erickson, Heidi; Kovacsovics, Tibor; O'Hare, Thomas; Heinrich, Michael C.; Druker, Brian J.

2009-01-01

Targeted therapy has vastly improved outcomes in certain types of cancer. Extension of this paradigm across a broad spectrum of malignancies will require an efficient method to determine the molecular vulnerabilities of cancerous cells. Improvements in sequencing technology will soon enable high-throughput sequencing of entire genomes of cancer patients; however, determining the relevance of identified sequence variants will require complementary functional analyses. Here, we report an RNAi-assisted protein target identification (RAPID) technology that individually assesses targeting of each member of the tyrosine kinase gene family. We demonstrate that RAPID screening of primary leukemia cells from 30 patients identifies targets that are critical to survival of the malignant cells from 10 of these individuals. We identify known, activating mutations in JAK2 and K-RAS, as well as patient-specific sensitivity to down-regulation of FLT1, CSF1R, PDGFR, ROR1, EPHA4/5, JAK1/3, LMTK3, LYN, FYN, PTK2B, and N-RAS. We also describe a previously undescribed, somatic, activating mutation in the thrombopoietin receptor that is sensitive to down-stream pharmacologic inhibition. Hence, the RAPID technique can quickly identify molecular vulnerabilities in malignant cells. Combination of this technique with whole-genome sequencing will represent an ideal tool for oncogenic target identification such that specific therapies can be matched with individual patients. PMID:19433805

The confidence-accuracy relationship in eyewitness identification: effects of lineup instructions, foil similarity, and target-absent base rates.

PubMed

Brewer, Neil; Wells, Gary L

2006-03-01

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 identifications from 8-person target-present or target-absent lineups. Confidence and accuracy were calibrated for choosers (but not nonchoosers) for both targets under all conditions. Lower overconfidence was associated with higher diagnosticity, lower target-absent base rates, and shorter identification latencies. Although researchers agree that courtroom expressions of confidence are uninformative, our findings indicate that confidence assessments obtained immediately after a positive identification can provide a useful guide for investigators about the likely accuracy of an identification.

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.

TargetMiner: microRNA target prediction with systematic identification of tissue-specific negative examples.

PubMed

Bandyopadhyay, Sanghamitra; Mitra, Ramkrishna

2009-10-15

Prediction of microRNA (miRNA) target mRNAs using machine learning approaches is an important area of research. However, most of the methods suffer from either high false positive or false negative rates. One reason for this is the marked deficiency of negative examples or miRNA non-target pairs. Systematic identification of non-target mRNAs is still not addressed properly, and therefore, current machine learning approaches are compelled to rely on artificially generated negative examples for training. In this article, we have identified approximately 300 tissue-specific negative examples using a novel approach that involves expression profiling of both miRNAs and mRNAs, miRNA-mRNA structural interactions and seed-site conservation. The newly generated negative examples are validated with pSILAC dataset, which elucidate the fact that the identified non-targets are indeed non-targets.These high-throughput tissue-specific negative examples and a set of experimentally verified positive examples are then used to build a system called TargetMiner, a support vector machine (SVM)-based classifier. In addition to assessing the prediction accuracy on cross-validation experiments, TargetMiner has been validated with a completely independent experimental test dataset. Our method outperforms 10 existing target prediction algorithms and provides a good balance between sensitivity and specificity that is not reflected in the existing methods. We achieve a significantly higher sensitivity and specificity of 69% and 67.8% based on a pool of 90 feature set and 76.5% and 66.1% using a set of 30 selected feature set on the completely independent test dataset. In order to establish the effectiveness of the systematically generated negative examples, the SVM is trained using a different set of negative data generated using the method in Yousef et al. A significantly higher false positive rate (70.6%) is observed when tested on the independent set, while all other factors are kept the

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.

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

PubMed

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

2016-09-23

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

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.

Identification of STAT target genes in adipocytes

PubMed Central

Zhao, Peng; Stephens, Jacqueline M.

2013-01-01

Adipocytes play important roles in lipid storage, energy homeostasis and whole body insulin sensitivity. Studies in the last two decades have identified the hormones and cytokines that activate specific STATs in adipocytes in vitro and in vivo. Five of the seven STAT family members are expressed in adipocyte (STATs 1, 3, 5A, 5B and 6). Many transcription factors, including STATs, have been shown to play an important role in adipose tissue development and function. This review will summarize the importance of adipocytes, indicate the cytokines and hormones that utilize the JAK-STAT signaling pathway in fat cells and focus on the identification of STAT target genes in mature adipocytes. To date, specific target genes have been identified for STATs, 1, 5A and 5B, but not for STATs 3 and 6. PMID:24058802

Identification of tissue-specific targeting peptide

NASA Astrophysics Data System (ADS)

Jung, Eunkyoung; Lee, Nam Kyung; Kang, Sang-Kee; Choi, Seung-Hoon; Kim, Daejin; Park, Kisoo; Choi, Kihang; Choi, Yun-Jaie; Jung, Dong Hyun

2012-11-01

Using phage display technique, we identified tissue-targeting peptide sets that recognize specific tissues (bone-marrow dendritic cell, kidney, liver, lung, spleen and visceral adipose tissue). In order to rapidly evaluate tissue-specific targeting peptides, we performed machine learning studies for predicting the tissue-specific targeting activity of peptides on the basis of peptide sequence information using four machine learning models and isolated the groups of peptides capable of mediating selective targeting to specific tissues. As a representative liver-specific targeting sequence, the peptide "DKNLQLH" was selected by the sequence similarity analysis. This peptide has a high degree of homology with protein ligands which can interact with corresponding membrane counterparts. We anticipate that our models will be applicable to the prediction of tissue-specific targeting peptides which can recognize the endothelial markers of target tissues.

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

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.

Exploring the effects of age and delay on children's person identifications: verbal descriptions, lineup performance, and the influence of wildcards.

PubMed

Karageorge, Aspasia; Zajac, Rachel

2011-05-01

We explored the effects of age and retention interval on several measures of children's person identification ability: verbal descriptions, lineup performance, and the success of a 'wildcard'--a photo of a silhouetted figure with a large question mark superimposed--in reducing children's tendency to choose from target-absent lineups. Children aged 5-7 years (N= 101) and 8-11 years (N= 109) were briefly exposed to an experimental confederate during a staged event. Either 1-2 days or 2 weeks later, children described the confederate and were then presented with either a target-present or -absent lineup. Within each group, approximately half of the children were presented with a wildcard and half were not. Target-present lineup performance improved as age increased. Compared to control children, children in the wildcard condition were more likely to correctly reject the target-absent lineup, and less likely to identify the innocent suspect. The wildcard did not influence children's target-present lineup accuracy, nor did delay exert an influence on any of our measures of lineup performance. These findings extend our knowledge of children's person identifications, as well as providing further support for the use of wildcards in photographic lineups. ©2010 The British Psychological Society.

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.

Atlas-based identification of targets for functional radiosurgery

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

Stancanello, Joseph; Romanelli, Pantaleo; Modugno, Nicola

2006-06-15

Functional disorders of the brain, such as Parkinson's disease, dystonia, epilepsy, and neuropathic pain, may exhibit poor response to medical therapy. In such cases, surgical intervention may become necessary. Modern surgical approaches to such disorders include radio-frequency lesioning and deep brain stimulation (DBS). The subthalamic nucleus (STN) is one of the most useful stereotactic targets available: STN DBS is known to induce substantial improvement in patients with end-stage Parkinson's disease. Other targets include the Globus Pallidus pars interna (GPi) for dystonia and Parkinson's disease, and the centromedian nucleus of the thalamus (CMN) for neuropathic pain. Radiosurgery is an attractive noninvasivemore » alternative to treat some functional brain disorders. The main technical limitation to radiosurgery is that the target can be selected only on the basis of magnetic resonance anatomy without electrophysiological confirmation. The aim of this work is to provide a method for the correct atlas-based identification of the target to be used in functional neurosurgery treatment planning. The coordinates of STN, CMN, and GPi were identified in the Talairach and Tournoux atlas and transformed to the corresponding regions of the Montreal Neurological Institute (MNI) electronic atlas. Binary masks describing the target nuclei were created. The MNI electronic atlas was deformed onto the patient magnetic resonance imaging-T1 scan by applying an affine transformation followed by a local nonrigid registration. The first transformation was based on normalized cross correlation and the second on optimization of a two-part objective function consisting of similarity criteria and weighted regularization. The obtained deformation field was then applied to the target masks. The minimum distance between the surface of an implanted electrode and the surface of the deformed mask was calculated. The validation of the method consisted of comparing the electrode

Performance characterization of a combined material identification and screening algorithm

NASA Astrophysics Data System (ADS)

Green, Robert L.; Hargreaves, Michael D.; Gardner, Craig M.

2013-05-01

Portable analytical devices based on a gamut of technologies (Infrared, Raman, X-Ray Fluorescence, Mass Spectrometry, etc.) are now widely available. These tools have seen increasing adoption for field-based assessment by diverse users including military, emergency response, and law enforcement. Frequently, end-users of portable devices are non-scientists who rely on embedded software and the associated algorithms to convert collected data into actionable information. Two classes of problems commonly encountered in field applications are identification and screening. Identification algorithms are designed to scour a library of known materials and determine whether the unknown measurement is consistent with a stored response (or combination of stored responses). Such algorithms can be used to identify a material from many thousands of possible candidates. Screening algorithms evaluate whether at least a subset of features in an unknown measurement correspond to one or more specific substances of interest and are typically configured to detect from a small list potential target analytes. Thus, screening algorithms are much less broadly applicable than identification algorithms; however, they typically provide higher detection rates which makes them attractive for specific applications such as chemical warfare agent or narcotics detection. This paper will present an overview and performance characterization of a combined identification/screening algorithm that has recently been developed. It will be shown that the combined algorithm provides enhanced detection capability more typical of screening algorithms while maintaining a broad identification capability. Additionally, we will highlight how this approach can enable users to incorporate situational awareness during a response.

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

PubMed

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

2014-06-30

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

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

PubMed

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

2014-06-01

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

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

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

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

Targeted nanodiamonds for identification of subcellular protein assemblies in mammalian cells

PubMed Central

Lake, Michael P.; Bouchard, Louis-S.

2017-01-01

Transmission electron microscopy (TEM) can be used to successfully determine the structures of proteins. However, such studies are typically done ex situ after extraction of the protein from the cellular environment. Here we describe an application for nanodiamonds as targeted intensity contrast labels in biological TEM, using the nuclear pore complex (NPC) as a model macroassembly. We demonstrate that delivery of antibody-conjugated nanodiamonds to live mammalian cells using maltotriose-conjugated polypropylenimine dendrimers results in efficient localization of nanodiamonds to the intended cellular target. We further identify signatures of nanodiamonds under TEM that allow for unambiguous identification of individual nanodiamonds from a resin-embedded, OsO4-stained environment. This is the first demonstration of nanodiamonds as labels for nanoscale TEM-based identification of subcellular protein assemblies. These results, combined with the unique fluorescence properties and biocompatibility of nanodiamonds, represent an important step toward the use of nanodiamonds as markers for correlated optical/electron bioimaging. PMID:28636640

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

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.

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.

Identification and validation nucleolin as a target of curcumol in nasopharyngeal carcinoma cells.

PubMed

Wang, Juan; Wu, Jiacai; Li, Xumei; Liu, Haowei; Qin, Jianli; Bai, Zhun; Chi, Bixia; Chen, Xu

2018-06-30

Identification of the specific protein target(s) of a drug is a critical step in unraveling its mechanisms of action (MOA) in many natural products. Curcumol, isolated from well known Chinese medicinal plant Curcuma zedoary, has been shown to possess multiple biological activities. It can inhibit nasopharyngeal carcinoma (NPC) proliferation and induce apoptosis, but its target protein(s) in NPC cells remains unclear. In this study, we employed a mass spectrometry-based chemical proteomics approach reveal the possible protein targets of curcumol in NPC cells. Cellular thermal shift assay (CETSA), molecular docking and cell-based assay was used to validate the binding interactions. Chemical proteomics capturing uncovered that NCL is a target of curcumol in NPC cells, Molecular docking showed that curcumol bound to NCL with an -7.8 kcal/mol binding free energy. Cell function analysis found that curcumol's treatment leads to a degradation of NCL in NPC cells, and it showed slight effects on NP69 cells. In conclusion, our results providing evidences that NCL is a target protein of curcumol. We revealed that the anti-cancer effects of curcumol in NPC cells are mediated, at least in part, by NCL inhibition. Many natural products showed high bioactivity, while their mechanisms of action (MOA) are very poor or completely missed. Understanding the MOA of natural drugs can thoroughly exploit their therapeutic potential and minimize their adverse side effects. Identification of the specific protein target(s) of a drug is a critical step in unraveling its MOA. Compound-centric chemical proteomics is a classic chemical proteomics approach which integrates chemical synthesis with cell biology and mass spectrometry (MS) to identify protein targets of natural products determine the drug mechanism of action, describe its toxicity, and figure out the possible cause of off-target. It is an affinity-based chemical proteomics method to identify small molecule-protein interactions

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

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.

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing.

PubMed

Lim, Hansaim; Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; He, Di; Zhuang, Luke; Meng, Patrick; Xie, Lei

2016-10-01

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and

Large-Scale Off-Target Identification Using Fast and Accurate Dual Regularized One-Class Collaborative Filtering and Its Application to Drug Repurposing

PubMed Central

Poleksic, Aleksandar; Yao, Yuan; Tong, Hanghang; Meng, Patrick; Xie, Lei

2016-01-01

Target-based screening is one of the major approaches in drug discovery. Besides the intended target, unexpected drug off-target interactions often occur, and many of them have not been recognized and characterized. The off-target interactions can be responsible for either therapeutic or side effects. Thus, identifying the genome-wide off-targets of lead compounds or existing drugs will be critical for designing effective and safe drugs, and providing new opportunities for drug repurposing. Although many computational methods have been developed to predict drug-target interactions, they are either less accurate than the one that we are proposing here or computationally too intensive, thereby limiting their capability for large-scale off-target identification. In addition, the performances of most machine learning based algorithms have been mainly evaluated to predict off-target interactions in the same gene family for hundreds of chemicals. It is not clear how these algorithms perform in terms of detecting off-targets across gene families on a proteome scale. Here, we are presenting a fast and accurate off-target prediction method, REMAP, which is based on a dual regularized one-class collaborative filtering algorithm, to explore continuous chemical space, protein space, and their interactome on a large scale. When tested in a reliable, extensive, and cross-gene family benchmark, REMAP outperforms the state-of-the-art methods. Furthermore, REMAP is highly scalable. It can screen a dataset of 200 thousands chemicals against 20 thousands proteins within 2 hours. Using the reconstructed genome-wide target profile as the fingerprint of a chemical compound, we predicted that seven FDA-approved drugs can be repurposed as novel anti-cancer therapies. The anti-cancer activity of six of them is supported by experimental evidences. Thus, REMAP is a valuable addition to the existing in silico toolbox for drug target identification, drug repurposing, phenotypic screening, and

Advances in the Study of Aptamer-Protein Target Identification Using the Chromatographic Approach.

PubMed

Drabik, Anna; Ner-Kluza, Joanna; Mielczarek, Przemyslaw; Civit, Laia; Mayer, Günter; Silberring, Jerzy

2018-06-01

Ever since the development of the process known as the systematic evolution of ligands by exponential enrichment (SELEX), aptamers have been widely used in a variety of studies, including the exploration of new diagnostic tools and the discovery of new treatment methods. Aptamers' ability to bind to proteins with high affinity and specificity, often compared to that of antibodies, enables the search for potential cancer biomarkers and helps us understand the mechanisms of carcinogenesis. The blind spot of those investigations is usually the difficulty in the selective extraction of targets attached to the aptamer. There are many studies describing the cell SELEX for the prime choice of aptamers toward living cancer cells or even whole tumors in the animal models. However, a dilemma arises when a large number of proteins are being identified as potential targets, which is often the case. In this article, we present a new analytical approach designed to selectively target proteins bound to aptamers. During studies, we have focused on the unambiguous identification of the molecular targets of aptamers characterized by high specificity to the prostate cancer cells. We have compared four assay approaches using electrophoretic and chromatographic methods for "fishing out" aptamer protein targets followed by mass spectrometry identification. We have established a new methodology, based on the fluorescent-tagged oligonucleotides commonly used for flow-cytometry experiments or as optic aptasensors, that allowed the detection of specific aptamer-protein interactions by mass spectrometry. The use of atto488-labeled aptamers for the tracking of the formation of specific aptamer-target complexes provides the possibility of studying putative protein counterparts without needing to apply enrichment techniques. Significantly, changes in the hydrophobic properties of atto488-labeled aptamer-protein complexes facilitate their separation by reverse-phase chromatography combined with

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.

The effects of platform motion and target orientation on the performance of trackball manipulation.

PubMed

Yau, Yi-Jan; Chao, Chin-Jung; Feng, Wen-Yang; Hwang, Sheue-Ling

2011-08-01

The trackball has been widely employed as a control/command input device on moving vehicles, but few studies have explored the effects of platform motion on its manipulation. Fewer still have considered this issue in designing the user interface and the arrangement of console location and orientation simultaneously. This work describes an experiment carried out to investigate the performance of trackball users on a simple point-and-click task in a motion simulator. By varying the orientation of onscreen targets, the effect of cursor movement direction on performance is investigated. The results indicate that the platform motion and target orientation both significantly affect the time required to point and click, but not the accuracy of target selection. The movement times were considerably longer under rolling and pitching motions and for targets located along the diagonal axes of the interface. Subjective evaluations carried out by the participants agree with these objective results. These findings could be used to optimise console and graphical menu design for use on maritime vessels. STATEMENT OF RELEVANCE: In military situations, matters of life or death may be decided in milliseconds. Any delay or error in classification and identification will thus affect the safety of the ship and its crew. This study demonstrates that performance of manipulating a trackball is affected by the platform motion and target orientation. The results of the present study can guide the arrangement of consoles and the design of trackball-based graphical user interfaces on maritime vessels.

Target Acquisition: Human Observer Performance Studies and TARGAC Model Validation

DTIC Science & Technology

1994-06-01

complete Scenario I run were displayed on a monitor. A transparent sheet was attached to the face of the monitor, the approach route was sketched on...track, passed a mark on the monitor face , the target was at a stop-sign location. The IRIG-B time of that instance was noted, and, since the distance of...route right 100- 80- 60 - 40 C.) 20 [- ion, A20 recognitio 0 0 . identification,C.) . 1I . I - - -• , 4) 1000 2000 3000 4000 SP Target G Q Target I0

Identification of regulatory targets of tissue-specific transcription factors: application to retina-specific gene regulation

PubMed Central

Qian, Jiang; Esumi, Noriko; Chen, Yangjian; Wang, Qingliang; Chowers, Itay; Zack, Donald J.

2005-01-01

Identification of tissue-specific gene regulatory networks can yield insights into the molecular basis of a tissue's development, function and pathology. Here, we present a computational approach designed to identify potential regulatory target genes of photoreceptor cell-specific transcription factors (TFs). The approach is based on the hypothesis that genes related to the retina in terms of expression, disease and/or function are more likely to be the targets of retina-specific TFs than other genes. A list of genes that are preferentially expressed in retina was obtained by integrating expressed sequence tag, SAGE and microarray datasets. The regulatory targets of retina-specific TFs are enriched in this set of retina-related genes. A Bayesian approach was employed to integrate information about binding site location relative to a gene's transcription start site. Our method was applied to three retina-specific TFs, CRX, NRL and NR2E3, and a number of potential targets were predicted. To experimentally assess the validity of the bioinformatic predictions, mobility shift, transient transfection and chromatin immunoprecipitation assays were performed with five predicted CRX targets, and the results were suggestive of CRX regulation in 5/5, 3/5 and 4/5 cases, respectively. Together, these experiments strongly suggest that RP1, GUCY2D, ABCA4 are novel targets of CRX. PMID:15967807

Decision time and confidence predict choosers' identification performance in photographic showups

PubMed Central

Sagana, Anna; Sporer, Siegfried L.; Wixted, John T.

2018-01-01

In vast contrast to the multitude of lineup studies that report on the link between decision time, confidence, and identification accuracy, only a few studies looked at these associations for showups, with results varying widely across studies. We therefore set out to test the individual and combined value of decision time and post-decision confidence for diagnosing the accuracy of positive showup decisions using confidence-accuracy characteristic curves and Bayesian analyses. Three-hundred-eighty-four participants viewed a stimulus event and were subsequently presented with two showups which could be target-present or target-absent. As expected, we found a negative decision time-accuracy and a positive post-decision confidence-accuracy correlation for showup selections. Confidence-accuracy characteristic curves demonstrated the expected additive effect of combining both postdictors. Likewise, Bayesian analyses, taking into account all possible target-presence base rate values showed that fast and confident identification decisions were more diagnostic than slow or less confident decisions, with the combination of both being most diagnostic for postdicting accurate and inaccurate decisions. The postdictive value of decision time and post-decision confidence was higher when the prior probability that the suspect is the perpetrator was high compared to when the prior probability that the suspect is the perpetrator was low. The frequent use of showups in practice emphasizes the importance of these findings for court proceedings. Overall, these findings support the idea that courts should have most trust in showup identifications that were made fast and confidently, and least in showup identifications that were made slowly and with low confidence. PMID:29346394

Decision time and confidence predict choosers' identification performance in photographic showups.

PubMed

Sauerland, Melanie; Sagana, Anna; Sporer, Siegfried L; Wixted, John T

2018-01-01

In vast contrast to the multitude of lineup studies that report on the link between decision time, confidence, and identification accuracy, only a few studies looked at these associations for showups, with results varying widely across studies. We therefore set out to test the individual and combined value of decision time and post-decision confidence for diagnosing the accuracy of positive showup decisions using confidence-accuracy characteristic curves and Bayesian analyses. Three-hundred-eighty-four participants viewed a stimulus event and were subsequently presented with two showups which could be target-present or target-absent. As expected, we found a negative decision time-accuracy and a positive post-decision confidence-accuracy correlation for showup selections. Confidence-accuracy characteristic curves demonstrated the expected additive effect of combining both postdictors. Likewise, Bayesian analyses, taking into account all possible target-presence base rate values showed that fast and confident identification decisions were more diagnostic than slow or less confident decisions, with the combination of both being most diagnostic for postdicting accurate and inaccurate decisions. The postdictive value of decision time and post-decision confidence was higher when the prior probability that the suspect is the perpetrator was high compared to when the prior probability that the suspect is the perpetrator was low. The frequent use of showups in practice emphasizes the importance of these findings for court proceedings. Overall, these findings support the idea that courts should have most trust in showup identifications that were made fast and confidently, and least in showup identifications that were made slowly and with low confidence.

Targeted sequencing of clade-specific markers from skin microbiomes for forensic human identification.

PubMed

Schmedes, Sarah E; Woerner, August E; Novroski, Nicole M M; Wendt, Frank R; King, Jonathan L; Stephens, Kathryn M; Budowle, Bruce

2018-01-01

The human skin microbiome is comprised of diverse communities of bacterial, eukaryotic, and viral taxa and contributes millions of additional genes to the repertoire of human genes, affecting human metabolism and immune response. Numerous genetic and environmental factors influence the microbiome composition and as such contribute to individual-specific microbial signatures which may be exploited for forensic applications. Previous studies have demonstrated the potential to associate skin microbial profiles collected from touched items to their individual owner, mainly using unsupervised methods from samples collected over short time intervals. Those studies utilize either targeted 16S rRNA or shotgun metagenomic sequencing to characterize skin microbiomes; however, these approaches have limited species and strain resolution and susceptibility to stochastic effects, respectively. Clade-specific markers from the skin microbiome, using supervised learning, can predict individual identity using skin microbiomes from their respective donors with high accuracy. In this study the hidSkinPlex is presented, a novel targeted sequencing method using skin microbiome markers developed for human identification. The hidSkinPlex (comprised of 286 bacterial (and phage) family-, genus-, species-, and subspecies-level markers), initially was evaluated on three bacterial control samples represented in the panel (i.e., Propionibacterium acnes, Propionibacterium granulosum, and Rothia dentocariosa) to assess the performance of the multiplex. The hidSkinPlex was further evaluated for prediction purposes. The hidSkinPlex markers were used to attribute skin microbiomes collected from eight individuals from three body sites (i.e., foot (Fb), hand (Hp) and manubrium (Mb)) to their host donor. Supervised learning, specifically regularized multinomial logistic regression and 1-nearest-neighbor classification were used to classify skin microbiomes to their hosts with up to 92% (Fb), 96% (Mb

Consistency of the Performance and Nonperformance Methods in Gifted Identification

ERIC Educational Resources Information Center

Acar, Selcuk; Sen, Sedat; Cayirdag, Nur

2016-01-01

Current approaches to gifted identification suggest collecting multiple sources of evidence. Some gifted identification guidelines allow for the interchangeable use of "performance" and "nonperformance" identification methods. This multiple criteria approach lacks a strong overlap between the assessment tools; however,…

Identification of Host-Targeted Small Molecules That Restrict Intracellular Mycobacterium tuberculosis Growth

PubMed Central

Silvis, Melanie R.; Luo, Samantha S.; Sogi, Kimberly; Vokes, Martha; Bray, Mark-Anthony; Carpenter, Anne E.; Moore, Christopher B.; Siddiqi, Noman; Rubin, Eric J.; Hung, Deborah T.

2014-01-01

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

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.

Systematic Identification of Combinatorial Drivers and Targets in Cancer Cell Lines

PubMed Central

Tabchy, Adel; Eltonsy, Nevine; Housman, David E.; Mills, Gordon B.

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance. PMID:23577104

Systematic identification of combinatorial drivers and targets in cancer cell lines.

PubMed

Tabchy, Adel; Eltonsy, Nevine; Housman, David E; Mills, Gordon B

2013-01-01

There is an urgent need to elicit and validate highly efficacious targets for combinatorial intervention from large scale ongoing molecular characterization efforts of tumors. We established an in silico bioinformatic platform in concert with a high throughput screening platform evaluating 37 novel targeted agents in 669 extensively characterized cancer cell lines reflecting the genomic and tissue-type diversity of human cancers, to systematically identify combinatorial biomarkers of response and co-actionable targets in cancer. Genomic biomarkers discovered in a 141 cell line training set were validated in an independent 359 cell line test set. We identified co-occurring and mutually exclusive genomic events that represent potential drivers and combinatorial targets in cancer. We demonstrate multiple cooperating genomic events that predict sensitivity to drug intervention independent of tumor lineage. The coupling of scalable in silico and biologic high throughput cancer cell line platforms for the identification of co-events in cancer delivers rational combinatorial targets for synthetic lethal approaches with a high potential to pre-empt the emergence of resistance.

SECOND TARGET STATION MODERATOR PERFORMANCE WITH A ROTATING TARGET

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

Remec, Igor; Gallmeier, Franz X; Rennich, Mark J

2016-01-01

Oak Ridge National Laboratory manages and operates the Spallation Neutron Source and the High Flux Isotope Reactor, two of the world's most advanced neutron scattering facilities. Both facilities are funded by the U.S. Department of Energy, Office of Science, Office of Basic Energy Science, and are available to researchers from all over the world. Delivering cutting edge science requires continuous improvements and development of the facilities and instruments. The SNS was designed from the outset to accommodate an additional target station, or Second Target Station (STS), and an upgraded accelerator feeding proton beams to STS and the existing First Targetmore » Station (FTS). Upgrade of the accelerator and the design and construction of STS are being proposed. The presently considered STS configuration is driven with short (<1 s) proton pulses at 10 Hz repetition rate and 467 kW proton beam power, and is optimized for high intensity and high resolution long wavelength neutron applications. STS will allow installation of 22 beamlines and will expand and complement the current national neutron scattering capabilities. In 2015 the STS studies were performed for a compact tungsten target; first a stationary tungsten plate target was analyzed to considerable details and then dropped in favor of a rotating target. For both target options the proton beam footprint as small as acceptable from mechanical and heat removal aspects is required to arrive at a compact-volume neutron production zone in the target, which is essential for tight coupling of target and moderators and for achieving high-intensity peak neutron fluxes. This paper will present recent STS work with the emphasis on neutronics and moderator performance.« less

Learning-based adaptive prescribed performance control of postcapture space robot-target combination without inertia identifications

NASA Astrophysics Data System (ADS)

Wei, Caisheng; Luo, Jianjun; Dai, Honghua; Bian, Zilin; Yuan, Jianping

2018-05-01

In this paper, a novel learning-based adaptive attitude takeover control method is investigated for the postcapture space robot-target combination with guaranteed prescribed performance in the presence of unknown inertial properties and external disturbance. First, a new static prescribed performance controller is developed to guarantee that all the involved attitude tracking errors are uniformly ultimately bounded by quantitatively characterizing the transient and steady-state performance of the combination. Then, a learning-based supplementary adaptive strategy based on adaptive dynamic programming is introduced to improve the tracking performance of static controller in terms of robustness and adaptiveness only utilizing the input/output data of the combination. Compared with the existing works, the prominent advantage is that the unknown inertial properties are not required to identify in the development of learning-based adaptive control law, which dramatically decreases the complexity and difficulty of the relevant controller design. Moreover, the transient and steady-state performance is guaranteed a priori by designer-specialized performance functions without resorting to repeated regulations of the controller parameters. Finally, the three groups of illustrative examples are employed to verify the effectiveness of the proposed control method.

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

Choking under the pressure of a positive stereotype: gender identification and self-consciousness moderate men's math test performance.

PubMed

Tagler, Michael J

2012-01-01

Choking under pressure occurs when an individual underperforms due to situational pressure. The present study examined whether being the target of a positive social stereotype regarding math ability causes choking among men. Gender identification and self-consciousness were hypothesized to moderate the effect of math-gender stereotypes on men's math test performance. Men high in self-consciousness but low in gender identification significantly underperformed when exposed to gender-relevant test instructions. No significant effects were found under a gender-irrelevant condition. These findings are discussed in the contexts of research on stereotype threat, stereotype lift, and choking under pressure.

Building face composites can harm lineup identification performance.

PubMed

Wells, Gary L; Charman, Steve D; Olson, Elizabeth A

2005-09-01

Face composite programs permit eyewitnesses to build likenesses of target faces by selecting facial features and combining them into an intact face. Research has shown that these composites are generally poor likenesses of the target face. Two experiments tested the proposition that this composite-building process could harm the builder's memory for the face. In Experiment 1 (n = 150), the authors used 50 different faces and found that the building of a composite reduced the chances that the person could later identify the original face from a lineup when compared with no composite control conditions or with yoked composite-exposure control conditions. In Experiment 2 (n = 200), the authors found that this effect generalized to a simulated-crime video, but mistaken identifications from target-absent lineups were not inflated by composite building. Copyright 2005 APA, all rights reserved.

Identification of Direct Target Genes Using Joint Sequence and Expression Likelihood with Application to DAF-16

PubMed Central

Yu, Ron X.; Liu, Jie; True, Nick; Wang, Wei

2008-01-01

A major challenge in the post-genome era is to reconstruct regulatory networks from the biological knowledge accumulated up to date. The development of tools for identifying direct target genes of transcription factors (TFs) is critical to this endeavor. Given a set of microarray experiments, a probabilistic model called TRANSMODIS has been developed which can infer the direct targets of a TF by integrating sequence motif, gene expression and ChIP-chip data. The performance of TRANSMODIS was first validated on a set of transcription factor perturbation experiments (TFPEs) involving Pho4p, a well studied TF in Saccharomyces cerevisiae. TRANSMODIS removed elements of arbitrariness in manual target gene selection process and produced results that concur with one's intuition. TRANSMODIS was further validated on a genome-wide scale by comparing it with two other methods in Saccharomyces cerevisiae. The usefulness of TRANSMODIS was then demonstrated by applying it to the identification of direct targets of DAF-16, a critical TF regulating ageing in Caenorhabditis elegans. We found that 189 genes were tightly regulated by DAF-16. In addition, DAF-16 has differential preference for motifs when acting as an activator or repressor, which awaits experimental verification. TRANSMODIS is computationally efficient and robust, making it a useful probabilistic framework for finding immediate targets. PMID:18350157

Performance Assessment of the CapitalBio Mycobacterium Identification Array System for Identification of Mycobacteria

PubMed Central

Liu, Jingbo; Yan, Zihe; Han, Min; Han, Zhijun; Jin, Lingjie; Zhao, Yanlin

2012-01-01

The CapitalBio Mycobacterium identification microarray system is a rapid system for the detection of Mycobacterium tuberculosis. The performance of this system was assessed with 24 reference strains, 486 Mycobacterium tuberculosis clinical isolates, and 40 clinical samples and then compared to the “gold standard” of DNA sequencing. The CapitalBio Mycobacterium identification microarray system showed highly concordant identification results of 100% and 98.4% for Mycobacterium tuberculosis complex (MTC) and nontuberculous mycobacteria (NTM), respectively. The sensitivity and specificity of the CapitalBio Mycobacterium identification array for identification of Mycobacterium tuberculosis isolates were 99.6% and 100%, respectively, for direct detection and identification of clinical samples, and the overall sensitivity was 52.5%. It was 100% for sputum, 16.7% for pleural fluid, and 10% for bronchoalveolar lavage fluid, respectively. The total assay was completed in 6 h, including DNA extraction, PCR, and hybridization. The results of this study confirm the utility of this system for the rapid identification of mycobacteria and suggest that the CapitalBio Mycobacterium identification array is a molecular diagnostic technique with high sensitivity and specificity that has the capacity to quickly identify most mycobacteria. PMID:22090408

Identification of Optimal Epitopes for Plasmodium falciparum Rapid Diagnostic Tests That Target Histidine-Rich Proteins 2 and 3

PubMed Central

Lee, Nelson; Gatton, Michelle L.; Pelecanos, Anita; Bubb, Martin; Gonzalez, Iveth; Bell, David; Cheng, Qin

2012-01-01

Rapid diagnostic tests (RDTs) represent important tools to diagnose malaria infection. To improve understanding of the variable performance of RDTs that detect the major target in Plasmodium falciparum, namely, histidine-rich protein 2 (HRP2), and to inform the design of better tests, we undertook detailed mapping of the epitopes recognized by eight HRP-specific monoclonal antibodies (MAbs). To investigate the geographic skewing of this polymorphic protein, we analyzed the distribution of these epitopes in parasites from geographically diverse areas. To identify an ideal amino acid motif for a MAb to target in HRP2 and in the related protein HRP3, we used a purpose-designed script to perform bioinformatic analysis of 448 distinct gene sequences from pfhrp2 and from 99 sequences from the closely related gene pfhrp3. The frequency and distribution of these motifs were also compared to the MAb epitopes. Heat stability testing of MAbs immobilized on nitrocellulose membranes was also performed. Results of these experiments enabled the identification of MAbs with the most desirable characteristics for inclusion in RDTs, including copy number and coverage of target epitopes, geographic skewing, heat stability, and match with the most abundant amino acid motifs identified. This study therefore informs the selection of MAbs to include in malaria RDTs as well as in the generation of improved MAbs that should improve the performance of HRP-detecting malaria RDTs. PMID:22259210

Identification of human microRNA targets from isolated argonaute protein complexes.

PubMed

Beitzinger, Michaela; Peters, Lasse; Zhu, Jia Yun; Kremmer, Elisabeth; Meister, Gunter

2007-06-01

MicroRNAs (miRNAs) constitute a class of small non-coding RNAs that regulate gene expression on the level of translation and/or mRNA stability. Mammalian miRNAs associate with members of the Argonaute (Ago) protein family and bind to partially complementary sequences in the 3' untranslated region (UTR) of specific target mRNAs. Computer algorithms based on factors such as free binding energy or sequence conservation have been used to predict miRNA target mRNAs. Based on such predictions, up to one third of all mammalian mRNAs seem to be under miRNA regulation. However, due to the low degree of complementarity between the miRNA and its target, such computer programs are often imprecise and therefore not very reliable. Here we report the first biochemical identification approach of miRNA targets from human cells. Using highly specific monoclonal antibodies against members of the Ago protein family, we co-immunoprecipitate Ago-bound mRNAs and identify them by cloning. Interestingly, most of the identified targets are also predicted by different computer programs. Moreover, we randomly analyzed six different target candidates and were able to experimentally validate five as miRNA targets. Our data clearly indicate that miRNA targets can be experimentally identified from Ago complexes and therefore provide a new tool to directly analyze miRNA function.

Fast identification of dermatophytes by MALDI-TOF/MS using direct transfer of fungal cells on ground steel target plates.

PubMed

da Cunha, Keith C; Riat, Arnaud; Normand, Anne-Cecile; Bosshard, Philipp P; de Almeida, Margarete T G; Piarroux, Renaud; Schrenzel, Jacques; Fontao, Lionel

2018-05-15

Dermatophytes cause human infections limited to keratinized tissues. We showed that the direct transfer method allows reliable identification of non-dermatophytes mould and yeast by MALDI-TOF/MS. We aimed at assessing whether the direct transfer method can be used for dermatophytes and whether an own mass spectra library would be superior to the Bruker library. We used the Bruker Biotyper to build a dermatophyte mass spectra library and assessed its performance by 1/ testing a panel of mass spectrum produced with strains genotypically identified and, 2/ comparing MALDI-TOF/MS identification to morphology-based methods. Identification of dermatophytes using the Bruker library is poor. Our library provided 97% concordance between ITS sequencing and MALDI-TOF/MS analysis with a panel of 1104 spectra corresponding to 276 strains. Direct transfer method using unpolished target plates allowed proper identification of 85% of dermatophytes clinical isolates most of which were common dermatophytes. A homemade dermatophyte MSP library is a prerequisite for accurate identification of species absent in the Bruker library but it also improves identification of species already listed in the database. The direct deposit method can be used to identify the most commonly found dermatophytes such as T. rubrum and T. interdigitale/mentagrophytes by MALDI-TOF/MS. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Genome-Wide Identification of CBX2 Targets: Insights in the Human Sex Development Network

PubMed Central

Eid, Wassim; Opitz, Lennart

2015-01-01

Chromobox homolog 2 (CBX2) is a chromatin modifier that plays an important role in sexual development and its disorders (disorders of sex development [DSD]), yet the exact rank and function of human CBX2 in this pathway remains unclear. Here, we performed large-scale mapping and analysis of in vivo target loci of the protein CBX2 in Sertoli-like NT-2D1 cells, using the DNA adenine methyltransferase identification technique. We identified close to 1600 direct targets for CBX2. Intriguingly, validation of selected candidate genes using qRT-PCR in cells overexpressing CBX2 or in which CBX2 has been knocked down indicated that several CBX2-responsive genes encode proteins that are involved in DSD. We further validated these effects on the candidate genes using a mutated CBX2 causing DSD in human patient. Overall, our findings suggest that CBX2 role in the sex development cascade is to stimulate the male pathway and concurrently inhibit the female pathway. These data provide fundamental insights into potential etiology of DSD. PMID:25569159

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").

Stereotype Threat in Classroom Settings: The Interactive Effect of Domain Identification, Task Difficulty and Stereotype Threat on Female Students' Maths Performance

ERIC Educational Resources Information Center

Keller, Johannes

2007-01-01

Background: Stereotype threat research revealed that negative stereotypes can disrupt the performance of persons targeted by such stereotypes. This paper contributes to stereotype threat research by providing evidence that domain identification and the difficulty level of test items moderate stereotype threat effects on female students' maths…

Computational Identification of MicroRNAs and Their Targets from Finger Millet (Eleusine coracana).

PubMed

Usha, S; Jyothi, M N; Suchithra, B; Dixit, Rekha; Rai, D V; Nagesh Babu, R

2017-03-01

MicroRNAs are endogenous small RNAs regulating intrinsic normal growth and development of plant. Discovering miRNAs, their targets and further inferring their functions had become routine process to comprehend the normal biological processes of miRNAs and their roles in plant development. In this study, we used homology-based analysis with available expressed sequence tag of finger millet (Eleusine coracana) to predict conserved miRNAs. Three potent miRNAs targeting 88 genes were identified. The newly identified miRNAs were found to be homologous with miR166 and miR1310. The targets recognized were transcription factors and enzymes, and GO analysis showed these miRNAs played varied roles in gene regulation. The identification of miRNAs and their targets is anticipated to hasten the pace of key epigenetic regulators in plant development.

Identification of Distant Drug Off-Targets by Direct Superposition of Binding Pocket Surfaces

PubMed Central

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”). PMID:24391782

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 2017 update: a web server for potential drug target identification with a comprehensive target pharmacophore database.

PubMed

Wang, Xia; Shen, Yihang; Wang, Shiwei; Li, Shiliang; Zhang, Weilin; Liu, Xiaofeng; Lai, Luhua; Pei, Jianfeng; Li, Honglin

2017-07-03

The PharmMapper online tool is a web server for potential drug target identification by reversed pharmacophore matching the query compound against an in-house pharmacophore model database. The original version of PharmMapper includes more than 7000 target pharmacophores derived from complex crystal structures with corresponding protein target annotations. In this article, we present a new version of the PharmMapper web server, of which the backend pharmacophore database is six times larger than the earlier one, with a total of 23 236 proteins covering 16 159 druggable pharmacophore models and 51 431 ligandable pharmacophore models. The expanded target data cover 450 indications and 4800 molecular functions compared to 110 indications and 349 molecular functions in our last update. In addition, the new web server is united with the statistically meaningful ranking of the identified drug targets, which is achieved through the use of standard scores. It also features an improved user interface. The proposed web server is freely available at http://lilab.ecust.edu.cn/pharmmapper/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

Performance Evaluation and Parameter Identification on DROID III

NASA Technical Reports Server (NTRS)

Plumb, Julianna J.

2011-01-01

The DROID III project consisted of two main parts. The former, performance evaluation, focused on the performance characteristics of the aircraft such as lift to drag ratio, thrust required for level flight, and rate of climb. The latter, parameter identification, focused on finding the aerodynamic coefficients for the aircraft using a system that creates a mathematical model to match the flight data of doublet maneuvers and the aircraft s response. Both portions of the project called for flight testing and that data is now available on account of this project. The conclusion of the project is that the performance evaluation data is well-within desired standards but could be improved with a thrust model, and that parameter identification is still in need of more data processing but seems to produce reasonable results thus far.

A new efficient method of generating photoaffinity beads for drug target identification.

PubMed

Nishiya, Yoichi; Hamada, Tomoko; Abe, Masayuki; Takashima, Michio; Tsutsumi, Kyoko; Okawa, Katsuya

2017-02-15

Affinity purification is one of the most prevalent methods for the target identification of small molecules. Preparation of an appropriate chemical for immobilization, however, is a tedious and time-consuming process. A decade ago, a photoreaction method for generating affinity beads was reported, where compounds are mixed with agarose beads carrying a photoreactive group (aryldiazirine) and then irradiated with ultraviolet light under dry conditions to form covalent attachment. Although the method has proven useful for identifying drug targets, the beads suffer from inefficient ligand incorporation and tend to shrink and aggregate, which can cause nonspecific binding and low reproducibility. We therefore decided to craft affinity beads free from these shortcomings without compromising the ease of preparation. We herein report a modified method; first, a compound of interest is mixed with a crosslinker having an activated ester and a photoreactive moiety on each end. This mixture is then dried in a glass tube and irradiated with ultraviolet light. Finally, the conjugates are dissolved and reacted with agarose beads with a primary amine. This protocol enabled us to immobilize compounds more efficiently (approximately 500-fold per bead compared to the original method) and generated beads without physical deterioration. We herein demonstrated that the new FK506-immobilized beads specifically isolated more FKBP12 than the original beads, thereby proving our method to be applicable to target identification experiments. Copyright © 2017 Elsevier Ltd. All rights reserved.

Applications of CRISPR genome editing technology in drug target identification and validation.

PubMed

Lu, Quinn; Livi, George P; Modha, Sundip; Yusa, Kosuke; Macarrón, Ricardo; Dow, David J

2017-06-01

The analysis of pharmaceutical industry data indicates that the major reason for drug candidates failing in late stage clinical development is lack of efficacy, with a high proportion of these due to erroneous hypotheses about target to disease linkage. More than ever, there is a requirement to better understand potential new drug targets and their role in disease biology in order to reduce attrition in drug development. Genome editing technology enables precise modification of individual protein coding genes, as well as noncoding regulatory sequences, enabling the elucidation of functional effects in human disease relevant cellular systems. Areas covered: This article outlines applications of CRISPR genome editing technology in target identification and target validation studies. Expert opinion: Applications of CRISPR technology in target validation studies are in evidence and gaining momentum. Whilst technical challenges remain, we are on the cusp of CRISPR being applied in complex cell systems such as iPS derived differentiated cells and stem cell derived organoids. In the meantime, our experience to date suggests that precise genome editing of putative targets in primary cell systems is possible, offering more human disease relevant systems than conventional cell lines.

A target and nontarget strategy for identification or characterization of the chemical ingredients in Chinese herb preparation Shuang-Huang-Lian oral liquid by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry.

PubMed

Zhang, Feng-Xiang; Li, Min; Yao, Zhi-Hong; Li, Chang; Qiao, Li-Rui; Shen, Xiu-Yu; Yu, Kate; Dai, Yi; Yao, Xin-Sheng

2018-03-01

A target and nontarget strategy based on in-house chemical components library was developed for rapid and comprehensive analysis of complicated components from traditional Chinese medicine preparation Shuang-Huang-Lian oral liquid. The sample was analyzed by ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry using generic acquisition parameters. Automated detection and data filtering were performed on the UNIFI™ software and the detected peaks were evaluated against an in-house library. As a result, a total of 170 chemical components (110 target compounds and 60 nontarget ones) were identified or tentatively characterized, including 54 flavonoids, 30 phenylethanoid glycosides, 16 iridoid glycosides, 14 lignans, 32 organic acids, 19 triterpenoid saponins and five other types of compounds. Among them, 44 compounds were further confirmed by comparison with reference standards. It was demonstrated that this systematical approach could be successfully applied for rapid identification of multiple compounds in traditional Chinese medicine and its preparations. Furthermore, this work established the foundation for the further investigation on the metabolic fates of multiple ingredients in Shuang-Huang-Lian oral liquid. Copyright © 2017 John Wiley & Sons, Ltd.

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

Improving scanner wafer alignment performance by target optimization

NASA Astrophysics Data System (ADS)

Leray, Philippe; Jehoul, Christiane; Socha, Robert; Menchtchikov, Boris; Raghunathan, Sudhar; Kent, Eric; Schoonewelle, Hielke; Tinnemans, Patrick; Tuffy, Paul; Belen, Jun; Wise, Rich

2016-03-01

In the process nodes of 10nm and below, the patterning complexity along with the processing and materials required has resulted in a need to optimize alignment targets in order to achieve the required precision, accuracy and throughput performance. Recent industry publications on the metrology target optimization process have shown a move from the expensive and time consuming empirical methodologies, towards a faster computational approach. ASML's Design for Control (D4C) application, which is currently used to optimize YieldStar diffraction based overlay (DBO) metrology targets, has been extended to support the optimization of scanner wafer alignment targets. This allows the necessary process information and design methodology, used for DBO target designs, to be leveraged for the optimization of alignment targets. In this paper, we show how we applied this computational approach to wafer alignment target design. We verify the correlation between predictions and measurements for the key alignment performance metrics and finally show the potential alignment and overlay performance improvements that an optimized alignment target could achieve.

Tactile Cueing for Target Acquisition and Identification

DTIC Science & Technology

2005-09-01

method of coding tactile information, and the method of presenting elevation information were studied. Results: Subjects were divided into video game experienced...VGP) subjects and non- video game (NVGP) experienced subjects. VGPs showed a significantly lower’ target acquisition time with the 12...that video game players performed better with the highest level of tactile resolution, while non- video game players performed better with simpler pattern and a lower resolution display.

Pharmacogenetics and target identification in diabetes.

PubMed

Pearson, Ewan R

2018-02-24

In diabetes, pharmacogenetics can be used both to identify patient subgroups who will have most benefit and/or least harm from a particularly treatment, and to gain insights into the molecular mechanisms of drug action and disease aetiology. There is increasing evidence that genetic variation alters response to diabetes treatments-both in terms of glycaemic response and side effects. This can be seen with dramatic impact on clinical care, in patients with genetic forms of diabetes such as Maturity Onset Diabetes of the Young caused by HNF1A mutations, and Neonatal diabetes due to activating mutations in ABCC8 or KCNJ11. Beyond monogenic diabetes, pharmacogenetic variants have yet to impact on clinical practice, yet the effect sizes (e.g. for metformin intolerance and OCT1 variants; or for metformin action and SLC2A2 variants) are potentially of clinical utility, especially if the genotype is already known at the point of prescribing. Over the next few years, increasing cohort sizes and linkage at scale to electronic medical records will provide considerable potential for stratification and novel target identification in diabetes. Copyright © 2018 Elsevier Ltd. All rights reserved.

Classification accuracy of claims-based methods for identifying providers failing to meet performance targets.

PubMed

Hubbard, Rebecca A; Benjamin-Johnson, Rhondee; Onega, Tracy; Smith-Bindman, Rebecca; Zhu, Weiwei; Fenton, Joshua J

2015-01-15

Quality assessment is critical for healthcare reform, but data sources are lacking for measurement of many important healthcare outcomes. With over 49 million people covered by Medicare as of 2010, Medicare claims data offer a potentially valuable source that could be used in targeted health care quality improvement efforts. However, little is known about the operating characteristics of provider profiling methods using claims-based outcome measures that may estimate provider performance with error. Motivated by the example of screening mammography performance, we compared approaches to identifying providers failing to meet guideline targets using Medicare claims data. We used data from the Breast Cancer Surveillance Consortium and linked Medicare claims to compare claims-based and clinical estimates of cancer detection rate. We then demonstrated the performance of claim-based estimates across a broad range of operating characteristics using simulation studies. We found that identification of poor performing providers was extremely sensitive to algorithm specificity, with no approach identifying more than 65% of poor performing providers when claims-based measures had specificity of 0.995 or less. We conclude that claims have the potential to contribute important information on healthcare outcomes to quality improvement efforts. However, to achieve this potential, development of highly accurate claims-based outcome measures should remain a priority. Copyright © 2014 John Wiley & Sons, Ltd.

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.

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.

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.

Texture metric that predicts target detection performance

NASA Astrophysics Data System (ADS)

Culpepper, Joanne B.

2015-12-01

Two texture metrics based on gray level co-occurrence error (GLCE) are used to predict probability of detection and mean search time. The two texture metrics are local clutter metrics and are based on the statistics of GLCE probability distributions. The degree of correlation between various clutter metrics and the target detection performance of the nine military vehicles in complex natural scenes found in the Search_2 dataset are presented. Comparison is also made between four other common clutter metrics found in the literature: root sum of squares, Doyle, statistical variance, and target structure similarity. The experimental results show that the GLCE energy metric is a better predictor of target detection performance when searching for targets in natural scenes than the other clutter metrics studied.

Meat Species Identification using Loop-mediated Isothermal Amplification Assay Targeting Species-specific Mitochondrial DNA.

PubMed

Cho, Ae-Ri; Dong, Hee-Jin; Cho, Seongbeom

2014-01-01

Meat source fraud and adulteration scandals have led to consumer demands for accurate meat identification methods. Nucleotide amplification assays have been proposed as an alternative method to protein-based assays for meat identification. In this study, we designed Loop-mediated isothermal amplification (LAMP) assays targeting species-specific mitochondrial DNA to identify and discriminate eight meat species; cattle, pig, horse, goat, sheep, chicken, duck, and turkey. The LAMP primer sets were designed and the target genes were discriminated according to their unique annealing temperature generated by annealing curve analysis. Their unique annealing temperatures were found to be 85.56±0.07℃ for cattle, 84.96±0.08℃ for pig, and 85.99±0.05℃ for horse in the BSE-LAMP set (Bos taurus, Sus scrofa domesticus and Equus caballus); 84.91±0.11℃ for goat and 83.90±0.11℃ for sheep in the CO-LAMP set (Capra hircus and Ovis aries); and 86.31±0.23℃ for chicken, 88.66±0.12℃ for duck, and 84.49±0.08℃ for turkey in the GAM-LAMP set (Gallus gallus, Anas platyrhynchos and Meleagris gallopavo). No cross-reactivity was observed in each set. The limits of detection (LODs) of the LAMP assays in raw and cooked meat were determined from 10 pg/μL to 100 fg/μL levels, and LODs in raw and cooked meat admixtures were determined from 0.01% to 0.0001% levels. The assays were performed within 30 min and showed greater sensitivity than that of the PCR assays. These novel LAMP assays provide a simple, rapid, accurate, and sensitive technology for discrimination of eight meat species.

Performance metrics for the evaluation of hyperspectral chemical identification systems

NASA Astrophysics Data System (ADS)

Truslow, Eric; Golowich, Steven; Manolakis, Dimitris; Ingle, Vinay

2016-02-01

Remote sensing of chemical vapor plumes is a difficult but important task for many military and civilian applications. Hyperspectral sensors operating in the long-wave infrared regime have well-demonstrated detection capabilities. However, the identification of a plume's chemical constituents, based on a chemical library, is a multiple hypothesis testing problem which standard detection metrics do not fully describe. We propose using an additional performance metric for identification based on the so-called Dice index. Our approach partitions and weights a confusion matrix to develop both the standard detection metrics and identification metric. Using the proposed metrics, we demonstrate that the intuitive system design of a detector bank followed by an identifier is indeed justified when incorporating performance information beyond the standard detection metrics.

Identification of the Downstream Promoter Targets of Smad Tumor Suppressors in Human Breast Cancer Cells

DTIC Science & Technology

2004-10-01

signaling mediator Smad2, Smad3 and Smad4 which form oligomeric complexes and migrate into nucleus to function as transcription factors to modulate... Smad3 and Smad4. 2. Identification of the downstream promoter targets of Smad3 or Smad4 in breast cancer cells. 3. Identify Smad4 regulated downstream...Development of a novel chromatin immunoprecipitation assay (CHIPS) using a TAP-TAG system to isolate in vivo binding targets of Smad3 and Smad4

Outperforming whom? A multilevel study of performance-prove goal orientation, performance, and the moderating role of shared team identification.

PubMed

Dietz, Bart; van Knippenberg, Daan; Hirst, Giles; Restubog, Simon Lloyd D

2015-11-01

Performance-prove goal orientation affects performance because it drives people to try to outperform others. A proper understanding of the performance-motivating potential of performance-prove goal orientation requires, however, that we consider the question of whom people desire to outperform. In a multilevel analysis of this issue, we propose that the shared team identification of a team plays an important moderating role here, directing the performance-motivating influence of performance-prove goal orientation to either the team level or the individual level of performance. A multilevel study of salespeople nested in teams supports this proposition, showing that performance-prove goal orientation motivates team performance more with higher shared team identification, whereas performance-prove goal orientation motivates individual performance more with lower shared team identification. Establishing the robustness of these findings, a second study replicates them with individual and team performance in an educational context. (c) 2015 APA, all rights reserved).

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.

Performance of an optical identification and interrogation system

NASA Astrophysics Data System (ADS)

Venugopalan, A.; Ghosh, A. K.; Verma, P.; Cheng, S.

2008-04-01

A free space optics based identification and interrogation system has been designed. The applications of the proposed system lie primarily in areas which require a secure means of mutual identification and information exchange between optical readers and tags. Conventional RFIDs raise issues regarding security threats, electromagnetic interference and health safety. The security of RF-ID chips is low due to the wide spatial spread of radio waves. Malicious nodes can read data being transmitted on the network, if they are in the receiving range. The proposed system provides an alternative which utilizes the narrow paraxial beams of lasers and an RSA-based authentication scheme. These provide enhanced security to communication between a tag and the base station or reader. The optical reader can also perform remote identification and the tag can be read from a far off distance, given line of sight. The free space optical identification and interrogation system can be used for inventory management, security systems at airports, port security, communication with high security systems, etc. to name a few. The proposed system was implemented with low-cost, off-the-shelf components and its performance in terms of throughput and bit error rate has been measured and analyzed. The range of operation with a bit-error-rate lower than 10-9 was measured to be about 4.5 m. The security of the system is based on the strengths of the RSA encryption scheme implemented using more than 1024 bits.

Identification of apoptosis-related PLZF target genes

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

Bernardo, Maria Victoria; Yelo, Estefania; Gimeno, Lourdes

2007-07-27

The PLZF gene encodes a BTB/POZ-zinc finger-type transcription factor, involved in physiological development, proliferation, differentiation, and apoptosis. In this paper, we investigate proliferation, survival, and gene expression regulation in stable clones from the human haematopoietic K562, DG75, and Jurkat cell lines with inducible expression of PLZF. In Jurkat cells, but not in K562 and DG75 cells, PLZF induced growth suppression and apoptosis in a cell density-dependent manner. Deletion of the BTB/POZ domain of PLZF abrogated growth suppression and apoptosis. PLZF was expressed with a nuclear speckled pattern distinctively in the full-length PLZF-expressing Jurkat clones, suggesting that the nuclear speckled localizationmore » is required for PLZF-induced apoptosis. By microarray analysis, we identified that the apoptosis-inducer TP53INP1, ID1, and ID3 genes were upregulated, and the apoptosis-inhibitor TERT gene was downregulated. The identification of apoptosis-related PLZF target genes may have biological and clinical relevance in cancer typified by altered PLZF expression.« less

Network Understanding of Herb Medicine via Rapid Identification of Ingredient-Target Interactions

NASA Astrophysics Data System (ADS)

Zhang, Hai-Ping; Pan, Jian-Bo; Zhang, Chi; Ji, Nan; Wang, Hao; Ji, Zhi-Liang

2014-01-01

Today, herb medicines have become the major source for discovery of novel agents in countermining diseases. However, many of them are largely under-explored in pharmacology due to the limitation of current experimental approaches. Therefore, we proposed a computational framework in this study for network understanding of herb pharmacology via rapid identification of putative ingredient-target interactions in human structural proteome level. A marketing anti-cancer herb medicine in China, Yadanzi (Brucea javanica), was chosen for mechanistic study. Total 7,119 ingredient-target interactions were identified for thirteen Yadanzi active ingredients. Among them, about 29.5% were estimated to have better binding affinity than their corresponding marketing drug-target interactions. Further Bioinformatics analyses suggest that simultaneous manipulation of multiple proteins in the MAPK signaling pathway and the phosphorylation process of anti-apoptosis may largely answer for Yadanzi against non-small cell lung cancers. In summary, our strategy provides an efficient however economic solution for systematic understanding of herbs' power.

Network understanding of herb medicine via rapid identification of ingredient-target interactions.

PubMed

Zhang, Hai-Ping; Pan, Jian-Bo; Zhang, Chi; Ji, Nan; Wang, Hao; Ji, Zhi-Liang

2014-01-16

Today, herb medicines have become the major source for discovery of novel agents in countermining diseases. However, many of them are largely under-explored in pharmacology due to the limitation of current experimental approaches. Therefore, we proposed a computational framework in this study for network understanding of herb pharmacology via rapid identification of putative ingredient-target interactions in human structural proteome level. A marketing anti-cancer herb medicine in China, Yadanzi (Brucea javanica), was chosen for mechanistic study. Total 7,119 ingredient-target interactions were identified for thirteen Yadanzi active ingredients. Among them, about 29.5% were estimated to have better binding affinity than their corresponding marketing drug-target interactions. Further Bioinformatics analyses suggest that simultaneous manipulation of multiple proteins in the MAPK signaling pathway and the phosphorylation process of anti-apoptosis may largely answer for Yadanzi against non-small cell lung cancers. In summary, our strategy provides an efficient however economic solution for systematic understanding of herbs' power.

Identification of Novel Molecular Targets for Endometrial Cancer Using a Drill-Down LC-MS/MS Approach with iTRAQ

PubMed Central

Voisin, Sébastien N.; Krakovska, Olga; Matta, Ajay; DeSouza, Leroi V.; Romaschin, Alexander D.; Colgan, Terence J.; Siu, K. W. Michael

2011-01-01

Background The number of patients with endometrial carcinoma (EmCa) with advanced stage or high histological grade is increasing and prognosis has not improved for over the last decade. There is an urgent need for the discovery of novel molecular targets for diagnosis, prognosis and treatment of EmCa, which will have the potential to improve the clinical strategy and outcome of this disease. Methodology and Results We used a “drill-down” proteomics approach to facilitate the identification of novel molecular targets for diagnosis, prognosis and/or therapeutic intervention for EmCa. Based on peptide ions identified and their retention times in the first LC-MS/MS analysis, an exclusion list was generated for subsequent iterations. A total of 1529 proteins have been identified below the Proteinpilot® 5% error threshold from the seven sets of iTRAQ experiments performed. On average, the second iteration added 78% new peptides to those identified after the first run, while the third iteration added 36% additional peptides. Of the 1529 proteins identified, only 40 satisfied our criteria for significant differential expression in EmCa in comparison to normal proliferative tissues. These proteins included metabolic enzymes (pyruvate kinase M2 and lactate dehydrogenase A); calcium binding proteins (S100A6, calcyphosine and calumenin), and proteins involved in regulating inflammation, proliferation and invasion (annexin A1, interleukin enhancer-binding factor 3, alpha-1-antitrypsin, macrophage capping protein and cathepsin B). Network analyses revealed regulation of these molecular targets by c-myc, Her2/neu and TNF alpha, suggesting intervention with these pathways may be a promising strategy for the development of novel molecular targeted therapies for EmCa. Conclusions Our analyses revealed the significance of drill-down proteomics approach in combination with iTRAQ to overcome some of the limitations of current proteomics strategies. This study led to the

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).

Parallel Analysis of 124 Universal SNPs for Human Identification by Targeted Semiconductor Sequencing

PubMed Central

Zhang, Suhua; Bian, Yingnan; Zhang, Zheren; Zheng, Hancheng; Wang, Zheng; Zha, Lagabaiyila; Cai, Jifeng; Gao, Yuzhen; Ji, Chaoneng; Hou, Yiping; Li, Chengtao

2015-01-01

SNPs, abundant in human genome with lower mutation rate, are attractive to genetic application like forensic, anthropological and evolutionary studies. Universal SNPs showing little allelic frequency variation among populations while remaining highly informative for human identification were obtained from previous studies. However, genotyping tools target only dozens of markers simultaneously, limiting their applications. Here, 124 SNPs were simultaneous tested using Ampliseq technology with Ion Torrent PGM platform. Concordance study was performed with 2 reference samples of 9947A and 9948 between NGS and Sanger sequencing. Full concordance were obtained except genotype of rs576261 with 9947A. Parameter of FMAR (%) was introduced for NGS data analysis for the first time, evaluating allelic performance, sensitivity testing and mixture testing. FMAR values for accurate heterozygotes should be range from 50% to 60%, for homozygotes or Y-SNP should be above 90%. SNPs of rs7520386, rs4530059, rs214955, rs1523537, rs2342747, rs576261 and rs12997453 were recognized as poorly performing loci, either with allelic imbalance or with lower coverage. Sensitivity testing demonstrated that with DNA range from 10 ng-0.5 ng, all correct genotypes were obtained. For mixture testing, a clear linear correlation (R2 = 0.9429) between the excepted FMAR and observed FMAR values of mixtures was observed. PMID:26691610

The Performance of Eyewitnesses with Intellectual Disabilities on Photographic Identification Line-Ups

ERIC Educational Resources Information Center

Wilcock, Rachel; Henry, Lucy

2013-01-01

Despite the large number of people with intellectual disabilities (ID) and the fact they are more likely to be victims and witnesses of crime, only two published studies have investigated their performance on identification line-up parades. In the present study we examined the identification performance of adults with and without ID on both a…

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.

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.

Microfluidic droplet enrichment for targeted sequencing

PubMed Central

Eastburn, Dennis J.; Huang, Yong; Pellegrino, Maurizio; Sciambi, Adam; Ptáček, Louis J.; Abate, Adam R.

2015-01-01

Targeted sequence enrichment enables better identification of genetic variation by providing increased sequencing coverage for genomic regions of interest. Here, we report the development of a new target enrichment technology that is highly differentiated from other approaches currently in use. Our method, MESA (Microfluidic droplet Enrichment for Sequence Analysis), isolates genomic DNA fragments in microfluidic droplets and performs TaqMan PCR reactions to identify droplets containing a desired target sequence. The TaqMan positive droplets are subsequently recovered via dielectrophoretic sorting, and the TaqMan amplicons are removed enzymatically prior to sequencing. We demonstrated the utility of this approach by generating an average 31.6-fold sequence enrichment across 250 kb of targeted genomic DNA from five unique genomic loci. Significantly, this enrichment enabled a more comprehensive identification of genetic polymorphisms within the targeted loci. MESA requires low amounts of input DNA, minimal prior locus sequence information and enriches the target region without PCR bias or artifacts. These features make it well suited for the study of genetic variation in a number of research and diagnostic applications. PMID:25873629

Target Abundance-Based Fitness Screening (TAFiS) Facilitates Rapid Identification of Target-Specific and Physiologically Active Chemical Probes

PubMed Central

Butts, Arielle; DeJarnette, Christian; Peters, Tracy L.; Parker, Josie E.; Kerns, Morgan E.; Eberle, Karen E.; Kelly, Steve L.

2017-01-01

-generation target-based whole-cell screening approach that incorporates the principles of both chemical genetics and competitive fitness, which enables the identification of target-specific and physiologically active compounds from a single screen. We have chosen to validate this approach using the important human fungal pathogen Candida albicans with the intention of pursuing novel antifungal targets. However, this approach is broadly applicable and is expected to dramatically reduce the time and resources required to progress from screening hit to lead compound. PMID:28989971

Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement

PubMed Central

Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan

2015-01-01

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. PMID:26582191

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.

Efficient Identification of Murine M2 Macrophage Peptide Targeting Ligands by Phage Display and Next-Generation Sequencing.

PubMed

Liu, Gary W; Livesay, Brynn R; Kacherovsky, Nataly A; Cieslewicz, Maryelise; Lutz, Emi; Waalkes, Adam; Jensen, Michael C; Salipante, Stephen J; Pun, Suzie H

2015-08-19

Peptide ligands are used to increase the specificity of drug carriers to their target cells and to facilitate intracellular delivery. One method to identify such peptide ligands, phage display, enables high-throughput screening of peptide libraries for ligands binding to therapeutic targets of interest. However, conventional methods for identifying target binders in a library by Sanger sequencing are low-throughput, labor-intensive, and provide a limited perspective (<0.01%) of the complete sequence space. Moreover, the small sample space can be dominated by nonspecific, preferentially amplifying "parasitic sequences" and plastic-binding sequences, which may lead to the identification of false positives or exclude the identification of target-binding sequences. To overcome these challenges, we employed next-generation Illumina sequencing to couple high-throughput screening and high-throughput sequencing, enabling more comprehensive access to the phage display library sequence space. In this work, we define the hallmarks of binding sequences in next-generation sequencing data, and develop a method that identifies several target-binding phage clones for murine, alternatively activated M2 macrophages with a high (100%) success rate: sequences and binding motifs were reproducibly present across biological replicates; binding motifs were identified across multiple unique sequences; and an unselected, amplified library accurately filtered out parasitic sequences. In addition, we validate the Multiple Em for Motif Elicitation tool as an efficient and principled means of discovering binding sequences.

Spatial frequency dependence of target signature for infrared performance modeling

NASA Astrophysics Data System (ADS)

Du Bosq, Todd; Olson, Jeffrey

2011-05-01

The standard model used to describe the performance of infrared imagers is the U.S. Army imaging system target acquisition model, based on the targeting task performance metric. The model is characterized by the resolution and sensitivity of the sensor as well as the contrast and task difficulty of the target set. The contrast of the target is defined as a spatial average contrast. The model treats the contrast of the target set as spatially white, or constant, over the bandlimit of the sensor. Previous experiments have shown that this assumption is valid under normal conditions and typical target sets. However, outside of these conditions, the treatment of target signature can become the limiting factor affecting model performance accuracy. This paper examines target signature more carefully. The spatial frequency dependence of the standard U.S. Army RDECOM CERDEC Night Vision 12 and 8 tracked vehicle target sets is described. The results of human perception experiments are modeled and evaluated using both frequency dependent and independent target signature definitions. Finally the function of task difficulty and its relationship to a target set is discussed.

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.

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...

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.

Experimental design and data analysis of Ago-RIP-Seq experiments for the identification of microRNA targets.

PubMed

Tichy, Diana; Pickl, Julia Maria Anna; Benner, Axel; Sültmann, Holger

2017-03-31

The identification of microRNA (miRNA) target genes is crucial for understanding miRNA function. Many methods for the genome-wide miRNA target identification have been developed in recent years; however, they have several limitations including the dependence on low-confident prediction programs and artificial miRNA manipulations. Ago-RNA immunoprecipitation combined with high-throughput sequencing (Ago-RIP-Seq) is a promising alternative. However, appropriate statistical data analysis algorithms taking into account the experimental design and the inherent noise of such experiments are largely lacking.Here, we investigate the experimental design for Ago-RIP-Seq and examine biostatistical methods to identify de novo miRNA target genes. Statistical approaches considered are either based on a negative binomial model fit to the read count data or applied to transformed data using a normal distribution-based generalized linear model. We compare them by a real data simulation study using plasmode data sets and evaluate the suitability of the approaches to detect true miRNA targets by sensitivity and false discovery rates. Our results suggest that simple approaches like linear regression models on (appropriately) transformed read count data are preferable. © The Author 2017. Published by Oxford University Press. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

A peptide-retrieval strategy enables significant improvement of quantitative performance without compromising confidence of identification.

PubMed

Tu, Chengjian; Shen, Shichen; Sheng, Quanhu; Shyr, Yu; Qu, Jun

2017-01-30

Reliable quantification of low-abundance proteins in complex proteomes is challenging largely owing to the limited number of spectra/peptides identified. In this study we developed a straightforward method to improve the quantitative accuracy and precision of proteins by strategically retrieving the less confident peptides that were previously filtered out using the standard target-decoy search strategy. The filtered-out MS/MS spectra matched to confidently-identified proteins were recovered, and the peptide-spectrum-match FDR were re-calculated and controlled at a confident level of FDR≤1%, while protein FDR maintained at ~1%. We evaluated the performance of this strategy in both spectral count- and ion current-based methods. >60% increase of total quantified spectra/peptides was respectively achieved for analyzing a spike-in sample set and a public dataset from CPTAC. Incorporating the peptide retrieval strategy significantly improved the quantitative accuracy and precision, especially for low-abundance proteins (e.g. one-hit proteins). Moreover, the capacity of confidently discovering significantly-altered proteins was also enhanced substantially, as demonstrated with two spike-in datasets. In summary, improved quantitative performance was achieved by this peptide recovery strategy without compromising confidence of protein identification, which can be readily implemented in a broad range of quantitative proteomics techniques including label-free or labeling approaches. We hypothesize that more quantifiable spectra and peptides in a protein, even including less confident peptides, could help reduce variations and improve protein quantification. Hence the peptide retrieval strategy was developed and evaluated in two spike-in sample sets with different LC-MS/MS variations using both MS1- and MS2-based quantitative approach. The list of confidently identified proteins using the standard target-decoy search strategy was fixed and more spectra/peptides with less

Performance Measurement and Target-Setting in California's Safety Net Health Systems.

PubMed

Hemmat, Shirin; Schillinger, Dean; Lyles, Courtney; Ackerman, Sara; Gourley, Gato; Vittinghoff, Eric; Handley, Margaret; Sarkar, Urmimala

Health policies encourage implementing quality measurement with performance targets. The 2010-2015 California Medicaid waiver mandated quality measurement and reporting. In 2013, California safety net hospitals participating in the waiver set a voluntary performance target (the 90th percentile for Medicare preferred provider organization plans) for mammography screening and cholesterol control in diabetes. They did not reach the target, and the difference-in-differences analysis suggested that there was no difference for mammography ( P = .39) and low-density lipoprotein control ( P = .11) performance compared to measures for which no statewide quality improvement initiative existed. California's Medicaid waiver was associated with improved performance on a number of metrics, but this performance was not attributable to target setting on specific health conditions. Performance may have improved because of secular trends or systems improvements related to waiver funding. Relying on condition-specific targets to measure performance may underestimate improvements and disadvantage certain health systems. Achieving ambitious targets likely requires sustained fiscal, management, and workforce investments.

The simulation study on optical target laser active detection performance

NASA Astrophysics Data System (ADS)

Li, Ying-chun; Hou, Zhao-fei; Fan, Youchen

2014-12-01

According to the working principle of laser active detection system, the paper establishes the optical target laser active detection simulation system, carry out the simulation study on the detection process and detection performance of the system. For instance, the performance model such as the laser emitting, the laser propagation in the atmosphere, the reflection of optical target, the receiver detection system, the signal processing and recognition. We focus on the analysis and modeling the relationship between the laser emitting angle and defocus amount and "cat eye" effect echo laser in the reflection of optical target. Further, in the paper some performance index such as operating range, SNR and the probability of the system have been simulated. The parameters including laser emitting parameters, the reflection of the optical target and the laser propagation in the atmosphere which make a great influence on the performance of the optical target laser active detection system. Finally, using the object-oriented software design methods, the laser active detection system with the opening type, complete function and operating platform, realizes the process simulation that the detection system detect and recognize the optical target, complete the performance simulation of each subsystem, and generate the data report and the graph. It can make the laser active detection system performance models more intuitive because of the visible simulation process. The simulation data obtained from the system provide a reference to adjust the structure of the system parameters. And it provides theoretical and technical support for the top level design of the optical target laser active detection system and performance index optimization.

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

NASA Astrophysics Data System (ADS)

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

2016-04-01

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

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

PubMed Central

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

2016-01-01

Identifying the molecular targets for the beneficial effects of active small-molecule compounds simultaneously is an important and currently unmet challenge. In this study, we firstly proposed network analysis by integrating data from network pharmacology and metabolomics to identify targets of active components in sini decoction (SND) simultaneously against heart failure. To begin with, 48 potential active components in SND against heart failure were predicted by serum pharmacochemistry, text mining and similarity match. Then, we employed network pharmacology including text mining and molecular docking to identify the potential targets of these components. The key enriched processes, pathways and related diseases of these target proteins were analyzed by STRING database. At last, network analysis was conducted to identify most possible targets of components in SND. Among the 25 targets predicted by network analysis, tumor necrosis factor α (TNF-α) was firstly experimentally validated in molecular and cellular level. Results indicated that hypaconitine, mesaconitine, higenamine and quercetin in SND can directly bind to TNF-α, reduce the TNF-α-mediated cytotoxicity on L929 cells and exert anti-myocardial cell apoptosis effects. We envisage that network analysis will also be useful in target identification of a bioactive compound. PMID:27095146

Clinical performance targets and quality of life in hemodialysis patients.

PubMed

Mazairac, Albert H A; de Wit, G Ardine; Grooteman, Muriel P C; Penne, E Lars; van der Weerd, Neelke C; den Hoedt, Claire H; Lévesque, Renée; van den Dorpel, Marinus A; Nubé, Menso J; Ter Wee, Piet M; Blankestijn, Peter J; Bots, Michiel L

2012-01-01

Patients value health-related quality of life (HRQOL) over survival. It was our aim to study the relation between attainment of widely accepted performance targets and HRQOL in hemodialysis patients. This study included baseline data from 715 hemodialysis patients from 29 dialysis centers. Six clinical performance targets, as recommended by the Kidney Disease Outcomes Quality Initiative (KDOQI), were evaluated: single-pool Kt/V (≥1.2), hemoglobin (11-13 g/dl), vascular access (fistula), phosphorus (2.3-4.5 mg/dl), parathyroid hormone (150-300 pg/ml), and blood pressure (predialysis <140/90 and postdialysis <130/ 80 mm Hg). After correction for case-mix and multiple comparisons, no association was found between the 6 KDOQI clinical performance targets and the 14 HRQOL domains, or between the number of performance targets reached and HRQOL. Attainment with widely accepted clinical performance targets was not related to the HRQOL of hemodialysis patients. Hence, in clinical guidelines, HRQOL should be adopted as an explicit treatment goal for these individuals. Copyright © 2011 S. Karger AG, Basel.

Automatic Target Recognition Based on Cross-Plot

PubMed Central

Wong, Kelvin Kian Loong; Abbott, Derek

2011-01-01

Automatic target recognition that relies on rapid feature extraction of real-time target from photo-realistic imaging will enable efficient identification of target patterns. To achieve this objective, Cross-plots of binary patterns are explored as potential signatures for the observed target by high-speed capture of the crucial spatial features using minimal computational resources. Target recognition was implemented based on the proposed pattern recognition concept and tested rigorously for its precision and recall performance. We conclude that Cross-plotting is able to produce a digital fingerprint of a target that correlates efficiently and effectively to signatures of patterns having its identity in a target repository. PMID:21980508

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

Pharmacologic Management of Duchenne Muscular Dystrophy: Target Identification and Preclinical Trials

PubMed Central

Kornegay, Joe N.; Spurney, Christopher F.; Nghiem, Peter P.; Brinkmeyer-Langford, Candice L.; Hoffman, Eric P.; Nagaraju, Kanneboyina

2014-01-01

Duchenne muscular dystrophy (DMD) is an X-linked human disorder in which absence of the protein dystrophin causes degeneration of skeletal and cardiac muscle. For the sake of treatment development, over and above definitive genetic and cell-based therapies, there is considerable interest in drugs that target downstream disease mechanisms. Drug candidates have typically been chosen based on the nature of pathologic lesions and presumed underlying mechanisms and then tested in animal models. Mammalian dystrophinopathies have been characterized in mice (mdx mouse) and dogs (golden retriever muscular dystrophy [GRMD]). Despite promising results in the mdx mouse, some therapies have not shown efficacy in DMD. Although the GRMD model offers a higher hurdle for translation, dogs have primarily been used to test genetic and cellular therapies where there is greater risk. Failed translation of animal studies to DMD raises questions about the propriety of methods and models used to identify drug targets and test efficacy of pharmacologic intervention. The mdx mouse and GRMD dog are genetically homologous to DMD but not necessarily analogous. Subcellular species differences are undoubtedly magnified at the whole-body level in clinical trials. This problem is compounded by disparate cultures in clinical trials and preclinical studies, pointing to a need for greater rigor and transparency in animal experiments. Molecular assays such as mRNA arrays and genome-wide association studies allow identification of genetic drug targets more closely tied to disease pathogenesis. Genes in which polymorphisms have been directly linked to DMD disease progression, as with osteopontin, are particularly attractive targets. PMID:24936034

Identification of novel plant peroxisomal targeting signals by a combination of machine learning methods and in vivo subcellular targeting analyses.

PubMed

Lingner, Thomas; Kataya, Amr R; Antonicelli, Gerardo E; Benichou, Aline; Nilssen, Kjersti; Chen, Xiong-Yan; Siemsen, Tanja; Morgenstern, Burkhard; Meinicke, Peter; Reumann, Sigrun

2011-04-01

In the postgenomic era, accurate prediction tools are essential for identification of the proteomes of cell organelles. Prediction methods have been developed for peroxisome-targeted proteins in animals and fungi but are missing specifically for plants. For development of a predictor for plant proteins carrying peroxisome targeting signals type 1 (PTS1), we assembled more than 2500 homologous plant sequences, mainly from EST databases. We applied a discriminative machine learning approach to derive two different prediction methods, both of which showed high prediction accuracy and recognized specific targeting-enhancing patterns in the regions upstream of the PTS1 tripeptides. Upon application of these methods to the Arabidopsis thaliana genome, 392 gene models were predicted to be peroxisome targeted. These predictions were extensively tested in vivo, resulting in a high experimental verification rate of Arabidopsis proteins previously not known to be peroxisomal. The prediction methods were able to correctly infer novel PTS1 tripeptides, which even included novel residues. Twenty-three newly predicted PTS1 tripeptides were experimentally confirmed, and a high variability of the plant PTS1 motif was discovered. These prediction methods will be instrumental in identifying low-abundance and stress-inducible peroxisomal proteins and defining the entire peroxisomal proteome of Arabidopsis and agronomically important crop plants.

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.

Comprehensive identification and structural characterization of target components from Gelsemium elegans by high-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry based on accurate mass databases combined with MS/MS spectra.

PubMed

Liu, Yan-Chun; Xiao, Sa; Yang, Kun; Ling, Li; Sun, Zhi-Liang; Liu, Zhao-Ying

2017-06-01

This study reports an applicable analytical strategy of comprehensive identification and structure characterization of target components from Gelsemium elegans by using high-performance liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QqTOF MS) based on the use of accurate mass databases combined with MS/MS spectra. The databases created included accurate masses and elemental compositions of 204 components from Gelsemium and their structural data. The accurate MS and MS/MS spectra were acquired through data-dependent auto MS/MS mode followed by an extraction of the potential compounds from the LC-QqTOF MS raw data of the sample. The same was matched using the databases to search for targeted components in the sample. The structures for detected components were tentatively characterized by manually interpreting the accurate MS/MS spectra for the first time. A total of 57 components have been successfully detected and structurally characterized from the crude extracts of G. elegans, but has failed to differentiate some isomers. This analytical strategy is generic and efficient, avoids isolation and purification procedures, enables a comprehensive structure characterization of target components of Gelsemium and would be widely applicable for complicated mixtures that are derived from Gelsemium preparations. Copyright © 2017 John Wiley & Sons, Ltd. Copyright © 2017 John Wiley & Sons, Ltd.

In Situ Identification of Cyanobacteria with Horseradish Peroxidase-Labeled, rRNA-Targeted Oligonucleotide Probes

PubMed Central

Schönhuber, Wilhelm; Zarda, Boris; Eix, Stella; Rippka, Rosmarie; Herdman, Michael; Ludwig, Wolfgang; Amann, Rudolf

1999-01-01

Individual cyanobacterial cells are normally identified in environmental samples only on the basis of their pigmentation and morphology. However, these criteria are often insufficient for the differentiation of species. Here, a whole-cell hybridization technique is presented that uses horseradish peroxidase (HRP)-labeled, rRNA-targeted oligonucleotides for in situ identification of cyanobacteria. This indirect method, in which the probe-conferred enzyme has to be visualized in an additional step, was necessary since fluorescently monolabeled oligonucleotides were insufficient to overstain the autofluorescence of the target cells. Initially, a nonfluorescent detection assay was developed and successfully applied to cyanobacterial mats. Later, it was demonstrated that tyramide signal amplification (TSA) resulted in fluorescent signals far above the level of autofluorescence. Furthermore, TSA-based detection of HRP was more sensitive than that based on nonfluorescent substrates. Critical points of the assay, such as cell fixation and permeabilization, specificity, and sensitivity, were systematically investigated by using four oligonucleotides newly designed to target groups of cyanobacteria. PMID:10049892

Performance comparison of denoising filters for source camera identification

NASA Astrophysics Data System (ADS)

Cortiana, A.; Conotter, V.; Boato, G.; De Natale, F. G. B.

2011-02-01

Source identification for digital content is one of the main branches of digital image forensics. It relies on the extraction of the photo-response non-uniformity (PRNU) noise as a unique intrinsic fingerprint that efficiently characterizes the digital device which generated the content. Such noise is estimated as the difference between the content and its de-noised version obtained via denoising filter processing. This paper proposes a performance comparison of different denoising filters for source identification purposes. In particular, results achieved with a sophisticated 3D filter are presented and discussed with respect to state-of-the-art denoising filters previously employed in such a context.

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

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

DTIC Science & Technology

2013-01-01

12 Palmer HG et al. The vitamin D receptor is a Wnt effector that controls hair follicle differentiation and specifies tumor type in adult epidermis...AD_________________ Award Number: W81XWH-11-1-0152 TITLE: Vitamin D pathway status and the...December 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER W81XWH-11-1-0152 Vitamin D pathway status and the identification of target genes in the

Performance enhancement for audio-visual speaker identification using dynamic facial muscle model.

PubMed

Asadpour, Vahid; Towhidkhah, Farzad; Homayounpour, Mohammad Mehdi

2006-10-01

Science of human identification using physiological characteristics or biometry has been of great concern in security systems. However, robust multimodal identification systems based on audio-visual information has not been thoroughly investigated yet. Therefore, the aim of this work to propose a model-based feature extraction method which employs physiological characteristics of facial muscles producing lip movements. This approach adopts the intrinsic properties of muscles such as viscosity, elasticity, and mass which are extracted from the dynamic lip model. These parameters are exclusively dependent on the neuro-muscular properties of speaker; consequently, imitation of valid speakers could be reduced to a large extent. These parameters are applied to a hidden Markov model (HMM) audio-visual identification system. In this work, a combination of audio and video features has been employed by adopting a multistream pseudo-synchronized HMM training method. Noise robust audio features such as Mel-frequency cepstral coefficients (MFCC), spectral subtraction (SS), and relative spectra perceptual linear prediction (J-RASTA-PLP) have been used to evaluate the performance of the multimodal system once efficient audio feature extraction methods have been utilized. The superior performance of the proposed system is demonstrated on a large multispeaker database of continuously spoken digits, along with a sentence that is phonetically rich. To evaluate the robustness of algorithms, some experiments were performed on genetically identical twins. Furthermore, changes in speaker voice were simulated with drug inhalation tests. In 3 dB signal to noise ratio (SNR), the dynamic muscle model improved the identification rate of the audio-visual system from 91 to 98%. Results on identical twins revealed that there was an apparent improvement on the performance for the dynamic muscle model-based system, in which the identification rate of the audio-visual system was enhanced from 87

Direct-to-consumer genetic testing for predicting sports performance and talent identification: Consensus statement.

PubMed

Webborn, Nick; Williams, Alun; McNamee, Mike; Bouchard, Claude; Pitsiladis, Yannis; Ahmetov, Ildus; Ashley, Euan; Byrne, Nuala; Camporesi, Silvia; Collins, Malcolm; Dijkstra, Paul; Eynon, Nir; Fuku, Noriyuki; Garton, Fleur C; Hoppe, Nils; Holm, Søren; Kaye, Jane; Klissouras, Vassilis; Lucia, Alejandro; Maase, Kamiel; Moran, Colin; North, Kathryn N; Pigozzi, Fabio; Wang, Guan

2015-12-01

The general consensus among sport and exercise genetics researchers is that genetic tests have no role to play in talent identification or the individualised prescription of training to maximise performance. Despite the lack of evidence, recent years have witnessed the rise of an emerging market of direct-to-consumer marketing (DTC) tests that claim to be able to identify children's athletic talents. Targeted consumers include mainly coaches and parents. There is concern among the scientific community that the current level of knowledge is being misrepresented for commercial purposes. There remains a lack of universally accepted guidelines and legislation for DTC testing in relation to all forms of genetic testing and not just for talent identification. There is concern over the lack of clarity of information over which specific genes or variants are being tested and the almost universal lack of appropriate genetic counselling for the interpretation of the genetic data to consumers. Furthermore independent studies have identified issues relating to quality control by DTC laboratories with different results being reported from samples from the same individual. Consequently, in the current state of knowledge, no child or young athlete should be exposed to DTC genetic testing to define or alter training or for talent identification aimed at selecting gifted children or adolescents. Large scale collaborative projects, may help to develop a stronger scientific foundation on these issues in the future. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

NASA Astrophysics Data System (ADS)

Gomer, Nathaniel R.; Gardner, Charles W.

2014-05-01

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

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

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

Identifiability and Performance Analysis of Output Over-sampling Approach to Direct Closed-loop Identification

NASA Astrophysics Data System (ADS)

Sun, Lianming; Sano, Akira

Output over-sampling based closed-loop identification algorithm is investigated in this paper. Some instinct properties of the continuous stochastic noise and the plant input, output in the over-sampling approach are analyzed, and they are used to demonstrate the identifiability in the over-sampling approach and to evaluate its identification performance. Furthermore, the selection of plant model order, the asymptotic variance of estimated parameters and the asymptotic variance of frequency response of the estimated model are also explored. It shows that the over-sampling approach can guarantee the identifiability and improve the performance of closed-loop identification greatly.

Target acquisition modeling over the exact optical path: extending the EOSTAR TDA with the TOD sensor performance model

NASA Astrophysics Data System (ADS)

Dijk, J.; Bijl, P.; Oppeneer, M.; ten Hove, R. J. M.; van Iersel, M.

2017-10-01

The Electro-Optical Signal Transmission and Ranging (EOSTAR) model is an image-based Tactical Decision Aid (TDA) for thermal imaging systems (MWIR/LWIR) developed for a sea environment with an extensive atmosphere model. The Triangle Orientation Discrimination (TOD) Target Acquisition model calculates the sensor and signal processing effects on a set of input triangle test pattern images, judges their orientation using humans or a Human Visual System (HVS) model and derives the system image quality and operational field performance from the correctness of the responses. Combination of the TOD model and EOSTAR, basically provides the possibility to model Target Acquisition (TA) performance over the exact path from scene to observer. In this method ship representative TOD test patterns are placed at the position of the real target, subsequently the combined effects of the environment (atmosphere, background, etc.), sensor and signal processing on the image are calculated using EOSTAR and finally the results are judged by humans. The thresholds are converted into Detection-Recognition-Identification (DRI) ranges of the real target. In experiments is shown that combination of the TOD model and the EOSTAR model is indeed possible. The resulting images look natural and provide insight in the possibilities of combining the two models. The TOD observation task can be done well by humans, and the measured TOD is consistent with analytical TOD predictions for the same camera that was modeled in the ECOMOS project.

Exploration of available feature detection and identification systems and their performance on radiographs

NASA Astrophysics Data System (ADS)

Wantuch, Andrew C.; Vita, Joshua A.; Jimenez, Edward S.; Bray, Iliana E.

2016-10-01

Despite object detection, recognition, and identification being very active areas of computer vision research, many of the available tools to aid in these processes are designed with only photographs in mind. Although some algorithms used specifically for feature detection and identification may not take explicit advantage of the colors available in the image, they still under-perform on radiographs, which are grayscale images. We are especially interested in the robustness of these algorithms, specifically their performance on a preexisting database of X-ray radiographs in compressed JPEG form, with multiple ways of describing pixel information. We will review various aspects of the performance of available feature detection and identification systems, including MATLABs Computer Vision toolbox, VLFeat, and OpenCV on our non-ideal database. In the process, we will explore possible reasons for the algorithms' lessened ability to detect and identify features from the X-ray radiographs.

Identification and Therapeutic Targeting of Paracrine Senescence Factors in the Prostate Tumor Microenvironment

DTIC Science & Technology

2011-03-01

UNIT NUMBER 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING ORGANIZATION REPORT NUMBER 9. SPONSORING...leading cause of cancer death in men in the United States - could be prevented with more effective treatments. Overcoming tumor cell resistance to...as described in prior reports. Recent work has focused on identification of possible functional effects of altered STC1 levels in the prostate tumor

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.

Identification of regulators of polyploidization presents therapeutic targets for treatment of AMKL.

PubMed

Wen, Qiang; Goldenson, Benjamin; Silver, Serena J; Schenone, Monica; Dancik, Vlado; Huang, Zan; Wang, Ling-Zhi; Lewis, Timothy A; An, W Frank; Li, Xiaoyu; Bray, Mark-Anthony; Thiollier, Clarisse; Diebold, Lauren; Gilles, Laure; Vokes, Martha S; Moore, Christopher B; Bliss-Moreau, Meghan; Verplank, Lynn; Tolliday, Nicola J; Mishra, Rama; Vemula, Sasidhar; Shi, Jianjian; Wei, Lei; Kapur, Reuben; Lopez, Cécile K; Gerby, Bastien; Ballerini, Paola; Pflumio, Francoise; Gilliland, D Gary; Goldberg, Liat; Birger, Yehudit; Izraeli, Shai; Gamis, Alan S; Smith, Franklin O; Woods, William G; Taub, Jeffrey; Scherer, Christina A; Bradner, James E; Goh, Boon-Cher; Mercher, Thomas; Carpenter, Anne E; Gould, Robert J; Clemons, Paul A; Carr, Steven A; Root, David E; Schreiber, Stuart L; Stern, Andrew M; Crispino, John D

2012-08-03

The mechanism by which cells decide to skip mitosis to become polyploid is largely undefined. Here we used a high-content image-based screen to identify small-molecule probes that induce polyploidization of megakaryocytic leukemia cells and serve as perturbagens to help understand this process. Our study implicates five networks of kinases that regulate the switch to polyploidy. Moreover, we find that dimethylfasudil (diMF, H-1152P) selectively increased polyploidization, mature cell-surface marker expression, and apoptosis of malignant megakaryocytes. An integrated target identification approach employing proteomic and shRNA screening revealed that a major target of diMF is Aurora kinase A (AURKA). We further find that MLN8237 (Alisertib), a selective inhibitor of AURKA, induced polyploidization and expression of mature megakaryocyte markers in acute megakaryocytic leukemia (AMKL) blasts and displayed potent anti-AMKL activity in vivo. Our findings provide a rationale to support clinical trials of MLN8237 and other inducers of polyploidization and differentiation in AMKL. Copyright © 2012 Elsevier Inc. All rights reserved.

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

Optical Quality, Threshold Target Identification, and Military Target Task Performance After Advanced Keratorefractive Surgery

DTIC Science & Technology

2012-05-01

undergo wavefront-guided (WFG) photorefractive keratectomy ( PRK ), WFG laser in situ keratomileusis ( LASIK ), wavefront optimized (WFO) PRK or WFO...Military, Refractive Surgery, PRK , LASIK , Night Vision, Wavefront Optimized, Wavefront Guided, Visual Performance, Quality of Vision, Outcomes...military. In a prospective, randomized treatment trial we will enroll 224 nearsighted soldiers to WFG photorefractive keratectomy ( PRK ), WFG LASIK , WFO PRK

Optical Quality, Threshold Target Identification and Military Target Task Performance After Advanced Keratorefractive Surgery

DTIC Science & Technology

2010-05-01

PRK vs . LASIK ) will no longer randomized but rather the patient a...commercial workstation & software. Analysis will determine the effect on visual performance of the different treatments (WFO PRK vs . WFO LASIK vs . WFG PRK ...Overall objective. To determine the effect of two types of wavefront modalities (WFG vs . WFO) and two types of refractive surgery ( PRK vs . LASIK )

Bootstrapping a de-identification system for narrative patient records: cost-performance tradeoffs.

PubMed

Hanauer, David; Aberdeen, John; Bayer, Samuel; Wellner, Benjamin; Clark, Cheryl; Zheng, Kai; Hirschman, Lynette

2013-09-01

We describe an experiment to build a de-identification system for clinical records using the open source MITRE Identification Scrubber Toolkit (MIST). We quantify the human annotation effort needed to produce a system that de-identifies at high accuracy. Using two types of clinical records (history and physical notes, and social work notes), we iteratively built statistical de-identification models by annotating 10 notes, training a model, applying the model to another 10 notes, correcting the model's output, and training from the resulting larger set of annotated notes. This was repeated for 20 rounds of 10 notes each, and then an additional 6 rounds of 20 notes each, and a final round of 40 notes. At each stage, we measured precision, recall, and F-score, and compared these to the amount of annotation time needed to complete the round. After the initial 10-note round (33min of annotation time) we achieved an F-score of 0.89. After just over 8h of annotation time (round 21) we achieved an F-score of 0.95. Number of annotation actions needed, as well as time needed, decreased in later rounds as model performance improved. Accuracy on history and physical notes exceeded that of social work notes, suggesting that the wider variety and contexts for protected health information (PHI) in social work notes is more difficult to model. It is possible, with modest effort, to build a functioning de-identification system de novo using the MIST framework. The resulting system achieved performance comparable to other high-performing de-identification systems. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Optical Quality, Threshold Target Identification, and Military Target Task Performance After Advanced Keratorefractive Surgery

DTIC Science & Technology

2011-05-01

WFG) photorefractive keratectomy (PRK), WFG laser in situ keratomileusis ( LASIK ), wavefront optimized (WFO) PRK or WFO LASIK (56 in each group...design will enable comparison to preoperative performance as well as comparisons between treatment groups. Military, Refractive Surgery, PRK, LASIK ...randomized treatment trial we will enroll 224 nearsighted soldiers to WFG photorefractive keratectomy (PRK), WFG LASIK , WFO PRK or WFO LASIK (56 in

Performance of Dower's inverse transform and Frank lead system for Identification of Myocardial Infarction.

PubMed

Aranda, A; Bonizzi, P; Karel, J; Peeters, R

2015-08-01

This study performs a comparison between Dower's inverse transform and Frank lead system for Myocardial Infarction (MI) identification. We have selected a set of relevant features for MI detection from the vectorcardiogram and used the lasso method after that to build a model for the Dower's inverse transform and one for the Frank leads system. Then we analyzed the performance between both models on MI detection. The proposed methods have been tested using PhysioNet PTB database that contains 550 records from which 368 are MIs. Two main conclusions are coming from this study. The first one is that Dower's inverse transform performs equally well than Frank leads in identification of MI patients. The second one is that lead positions have a large influence on the accuracy of MI patient identification.

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.

High-throughput identification of off-targets for the mechanistic study of severe adverse drug reactions induced by analgesics

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

Pan, Jian-Bo; Ji, Nan; Pan, Wen

2014-01-01

Drugs may induce adverse drug reactions (ADRs) when they unexpectedly bind to proteins other than their therapeutic targets. Identification of these undesired protein binding partners, called off-targets, can facilitate toxicity assessment in the early stages of drug development. In this study, a computational framework was introduced for the exploration of idiosyncratic mechanisms underlying analgesic-induced severe adverse drug reactions (SADRs). The putative analgesic-target interactions were predicted by performing reverse docking of analgesics or their active metabolites against human/mammal protein structures in a high-throughput manner. Subsequently, bioinformatics analyses were undertaken to identify ADR-associated proteins (ADRAPs) and pathways. Using the pathways and ADRAPsmore » that this analysis identified, the mechanisms of SADRs such as cardiac disorders were explored. For instance, 53 putative ADRAPs and 24 pathways were linked with cardiac disorders, of which 10 ADRAPs were confirmed by previous experiments. Moreover, it was inferred that pathways such as base excision repair, glycolysis/glyconeogenesis, ErbB signaling, calcium signaling, and phosphatidyl inositol signaling likely play pivotal roles in drug-induced cardiac disorders. In conclusion, our framework offers an opportunity to globally understand SADRs at the molecular level, which has been difficult to realize through experiments. It also provides some valuable clues for drug repurposing. - Highlights: • A novel computational framework was developed for mechanistic study of SADRs. • Off-targets of drugs were identified in large scale and in a high-throughput manner. • SADRs like cardiac disorders were systematically explored in molecular networks. • A number of ADR-associated proteins were identified.« less

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

PubMed

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

2015-01-01

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

New support vector machine-based method for microRNA target prediction.

PubMed

Li, L; Gao, Q; Mao, X; Cao, Y

2014-06-09

MicroRNA (miRNA) plays important roles in cell differentiation, proliferation, growth, mobility, and apoptosis. An accurate list of precise target genes is necessary in order to fully understand the importance of miRNAs in animal development and disease. Several computational methods have been proposed for miRNA target-gene identification. However, these methods still have limitations with respect to their sensitivity and accuracy. Thus, we developed a new miRNA target-prediction method based on the support vector machine (SVM) model. The model supplies information of two binding sites (primary and secondary) for a radial basis function kernel as a similarity measure for SVM features. The information is categorized based on structural, thermodynamic, and sequence conservation. Using high-confidence datasets selected from public miRNA target databases, we obtained a human miRNA target SVM classifier model with high performance and provided an efficient tool for human miRNA target gene identification. Experiments have shown that our method is a reliable tool for miRNA target-gene prediction, and a successful application of an SVM classifier. Compared with other methods, the method proposed here improves the sensitivity and accuracy of miRNA prediction. Its performance can be further improved by providing more training examples.

Information Feedback: Contributions to Learning and Performance in Perceptual Identification Training.

ERIC Educational Resources Information Center

Abrams, Alvin J.; Cook, Richard L.

In training people to perform auditory identification tasks (e.g., training students to identify sound characteristics in a sonar classification task), it is important to know whether or not training procedures are merely sustaining performance during training or whether they enhance learning of the task. Often an incorrect assumption is made that…

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...

The Impact of Early Design Phase Risk Identification Biases on Space System Project Performance

NASA Technical Reports Server (NTRS)

Reeves, John D., Jr.; Eveleigh, Tim; Holzer, Thomas; Sarkani, Shahryar

2012-01-01

Risk identification during the early design phases of complex systems is commonly implemented but often fails to result in the identification of events and circumstances that truly challenge project performance. Inefficiencies in cost and schedule estimation are usually held accountable for cost and schedule overruns, but the true root cause is often the realization of programmatic risks. A deeper understanding of frequent risk identification trends and biases pervasive during space system design and development is needed, for it would lead to improved execution of existing identification processes and methods.

Core Proteomic Analysis of Unique Metabolic Pathways of Salmonella enterica for the Identification of Potential Drug Targets.

PubMed

Uddin, Reaz; Sufian, Muhammad

2016-01-01

Infections caused by Salmonella enterica, a Gram-negative facultative anaerobic bacteria belonging to the family of Enterobacteriaceae, are major threats to the health of humans and animals. The recent availability of complete genome data of pathogenic strains of the S. enterica gives new avenues for the identification of drug targets and drug candidates. We have used the genomic and metabolic pathway data to identify pathways and proteins essential to the pathogen and absent from the host. We took the whole proteome sequence data of 42 strains of S. enterica and Homo sapiens along with KEGG-annotated metabolic pathway data, clustered proteins sequences using CD-HIT, identified essential genes using DEG database and discarded S. enterica homologs of human proteins in unique metabolic pathways (UMPs) and characterized hypothetical proteins with SVM-prot and InterProScan. Through this core proteomic analysis we have identified enzymes essential to the pathogen. The identification of 73 enzymes common in 42 strains of S. enterica is the real strength of the current study. We proposed all 73 unexplored enzymes as potential drug targets against the infections caused by the S. enterica. The study is comprehensive around S. enterica and simultaneously considered every possible pathogenic strain of S. enterica. This comprehensiveness turned the current study significant since, to the best of our knowledge it is the first subtractive core proteomic analysis of the unique metabolic pathways applied to any pathogen for the identification of drug targets. We applied extensive computational methods to shortlist few potential drug targets considering the druggability criteria e.g. Non-homologous to the human host, essential to the pathogen and playing significant role in essential metabolic pathways of the pathogen (i.e. S. enterica). In the current study, the subtractive proteomics through a novel approach was applied i.e. by considering only proteins of the unique metabolic

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

Rapid computational identification of the targets of protein kinase inhibitors.

PubMed

Rockey, William M; Elcock, Adrian H

2005-06-16

We describe a method for rapidly computing the relative affinities of an inhibitor for all individual members of a family of homologous receptors. The approach, implemented in a new program, SCR, models inhibitor-receptor interactions in full atomic detail with an empirical energy function and includes an explicit account of flexibility in homology-modeled receptors through sampling of libraries of side chain rotamers. SCR's general utility was demonstrated by application to seven different protein kinase inhibitors: for each inhibitor, relative binding affinities with panels of approximately 20 protein kinases were computed and compared with experimental data. For five of the inhibitors (SB203580, purvalanol B, imatinib, H89, and hymenialdisine), SCR provided excellent reproduction of the experimental trends and, importantly, was capable of identifying the targets of inhibitors even when they belonged to different kinase families. The method's performance in a predictive setting was demonstrated by performing separate training and testing applications, and its key assumptions were tested by comparison with a number of alternative approaches employing the ligand-docking program AutoDock (Morris et al. J. Comput. Chem. 1998, 19, 1639-1662). These comparison tests included using AutoDock in nondocking and docking modes and performing energy minimizations of inhibitor-kinase complexes with the molecular mechanics code GROMACS (Berendsen et al. Comput. Phys. Commun. 1995, 91, 43-56). It was found that a surprisingly important aspect of SCR's approach is its assumption that the inhibitor be modeled in the same orientation for each kinase: although this assumption is in some respects unrealistic, calculations that used apparently more realistic approaches produced clearly inferior results. Finally, as a large-scale application of the method, SB203580, purvalanol B, and imatinib were screened against an almost full complement of 493 human protein kinases using SCR in

Modeling Spoken Word Recognition Performance by Pediatric Cochlear Implant Users using Feature Identification

PubMed Central

Frisch, Stefan A.; Pisoni, David B.

2012-01-01

Objective Computational simulations were carried out to evaluate the appropriateness of several psycholinguistic theories of spoken word recognition for children who use cochlear implants. These models also investigate the interrelations of commonly used measures of closed-set and open-set tests of speech perception. Design A software simulation of phoneme recognition performance was developed that uses feature identification scores as input. Two simulations of lexical access were developed. In one, early phoneme decisions are used in a lexical search to find the best matching candidate. In the second, phoneme decisions are made only when lexical access occurs. Simulated phoneme and word identification performance was then applied to behavioral data from the Phonetically Balanced Kindergarten test and Lexical Neighborhood Test of open-set word recognition. Simulations of performance were evaluated for children with prelingual sensorineural hearing loss who use cochlear implants with the MPEAK or SPEAK coding strategies. Results Open-set word recognition performance can be successfully predicted using feature identification scores. In addition, we observed no qualitative differences in performance between children using MPEAK and SPEAK, suggesting that both groups of children process spoken words similarly despite differences in input. Word recognition ability was best predicted in the model in which phoneme decisions were delayed until lexical access. Conclusions Closed-set feature identification and open-set word recognition focus on different, but related, levels of language processing. Additional insight for clinical intervention may be achieved by collecting both types of data. The most successful model of performance is consistent with current psycholinguistic theories of spoken word recognition. Thus it appears that the cognitive process of spoken word recognition is fundamentally the same for pediatric cochlear implant users and children and adults with

Stereotype threat in classroom settings: the interactive effect of domain identification, task difficulty and stereotype threat on female students' maths performance.

PubMed

Keller, Johannes

2007-06-01

Stereotype threat research revealed that negative stereotypes can disrupt the performance of persons targeted by such stereotypes. This paper contributes to stereotype threat research by providing evidence that domain identification and the difficulty level of test items moderate stereotype threat effects on female students' maths performance. The study was designed to test theoretical ideas derived from stereotype threat theory and assumptions outlined in the Yerkes-Dodson law proposing a nonlinear relationship between arousal, task difficulty and performance. Participants were 108 high school students attending secondary schools. Participants worked on a test comprising maths problems of different difficulty levels. Half of the participants learned that the test had been shown to produce gender differences (stereotype threat). The other half learned that the test had been shown not to produce gender differences (no threat). The degree to which participants identify with the domain of maths was included as a quasi-experimental factor. Maths-identified female students showed performance decrements under conditions of stereotype threat. Moreover, the stereotype threat manipulation had different effects on low and high domain identifiers' performance depending on test item difficulty. On difficult items, low identifiers showed higher performance under threat (vs. no threat) whereas the reverse was true in high identifiers. This interaction effect did not emerge on easy items. Domain identification and test item difficulty are two important factors that need to be considered in the attempt to understand the impact of stereotype threat on performance.

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.

Target identification by image analysis.

PubMed

Fetz, V; Prochnow, H; Brönstrup, M; Sasse, F

2016-05-04

Covering: 1997 to the end of 2015Each biologically active compound induces phenotypic changes in target cells that are characteristic for its mode of action. These phenotypic alterations can be directly observed under the microscope or made visible by labelling structural elements or selected proteins of the cells with dyes. A comparison of the cellular phenotype induced by a compound of interest with the phenotypes of reference compounds with known cellular targets allows predicting its mode of action. While this approach has been successfully applied to the characterization of natural products based on a visual inspection of images, recent studies used automated microscopy and analysis software to increase speed and to reduce subjective interpretation. In this review, we give a general outline of the workflow for manual and automated image analysis, and we highlight natural products whose bacterial and eucaryotic targets could be identified through such approaches.

Distress identification manual for the long-term pavement performance program (Fifth revised edition)

DOT National Transportation Integrated Search

2014-05-01

Accurate, consistent, and repeatable distress evaluation surveys can be performed by using the Distress Identification Manual for the Long-Term Pavement Performance Program. Color photographs and drawings illustrate the distresses found in three basi...

Drug target identification in protozoan parasites.

PubMed

Müller, Joachim; Hemphill, Andrew

2016-08-01

Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses.

Drug target identification in protozoan parasites

PubMed Central

Müller, Joachim; Hemphill, Andrew

2016-01-01

Introduction Despite the fact that diseases caused by protozoan parasites represent serious challenges for public health, animal production and welfare, only a limited panel of drugs has been marketed for clinical applications. Areas covered Herein, the authors investigate two strategies, namely whole organism screening and target-based drug design. The present pharmacopoeia has resulted from whole organism screening, and the mode of action and targets of selected drugs are discussed. However, the more recent extensive genome sequencing efforts and the development of dry and wet lab genomics and proteomics that allow high-throughput screening of interactions between micromolecules and recombinant proteins has resulted in target-based drug design as the predominant focus in anti-parasitic drug development. Selected examples of target-based drug design studies are presented, and calcium-dependent protein kinases, important drug targets in apicomplexan parasites, are discussed in more detail. Expert opinion Despite the enormous efforts in target-based drug development, this approach has not yet generated market-ready antiprotozoal drugs. However, whole-organism screening approaches, comprising of both in vitro and in vivo investigations, should not be disregarded. The repurposing of already approved and marketed drugs could be a suitable strategy to avoid fastidious approval procedures, especially in the case of neglected or veterinary parasitoses. PMID:27238605

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.

Enhancing bioactive peptide release and identification using targeted enzymatic hydrolysis of milk proteins.

PubMed

Nongonierma, Alice B; FitzGerald, Richard J

2018-06-01

Milk proteins have been extensively studied for their ability to yield a range of bioactive peptides following enzymatic hydrolysis/digestion. However, many hurdles still exist regarding the widespread utilization of milk protein-derived bioactive peptides as health enhancing agents for humans. These mostly arise from the fact that most milk protein-derived bioactive peptides are not highly potent. In addition, they may be degraded during gastrointestinal digestion and/or have a low intestinal permeability. The targeted release of bioactive peptides during the enzymatic hydrolysis of milk proteins may allow the generation of particularly potent bioactive hydrolysates and peptides. Therefore, the development of milk protein hydrolysates capable of improving human health requires, in the first instance, optimized targeted release of specific bioactive peptides. The targeted hydrolysis of milk proteins has been aided by a range of in silico tools. These include peptide cutters and predictive modeling linking bioactivity to peptide structure [i.e., molecular docking, quantitative structure activity relationship (QSAR)], or hydrolysis parameters [design of experiments (DOE)]. Different targeted enzymatic release strategies employed during the generation of milk protein hydrolysates are reviewed herein and their limitations are outlined. In addition, specific examples are provided to demonstrate how in silico tools may help in the identification and discovery of potent milk protein-derived peptides. It is anticipated that the development of novel strategies employing a range of in silico tools may help in the generation of milk protein hydrolysates containing potent and bioavailable peptides, which in turn may be used to validate their health promoting effects in humans. Graphical abstract The targeted enzymatic hydrolysis of milk proteins may allow the generation of highly potent and bioavailable bioactive peptides.

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.

Investigating effects of communications modulation technique on targeting performance

NASA Astrophysics Data System (ADS)

Blasch, Erik; Eusebio, Gerald; Huling, Edward

2006-05-01

One of the key challenges facing the global war on terrorism (GWOT) and urban operations is the increased need for rapid and diverse information from distributed sources. For users to get adequate information on target types and movements, they would need reliable data. In order to facilitate reliable computational intelligence, we seek to explore the communication modulation tradeoffs affecting information distribution and accumulation. In this analysis, we explore the modulation techniques of Orthogonal Frequency Division Multiplexing (OFDM), Direct Sequence Spread Spectrum (DSSS), and statistical time-division multiple access (TDMA) as a function of the bit error rate and jitter that affect targeting performance. In the analysis, we simulate a Link 16 with a simple bandpass frequency shift keying (PSK) technique using different Signal-to-Noise ratios. The communications transfer delay and accuracy tradeoffs are assessed as to the effects incurred in targeting performance.

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.

Dynamic neural networks based on-line identification and control of high performance motor drives

NASA Technical Reports Server (NTRS)

Rubaai, Ahmed; Kotaru, Raj

1995-01-01

In the automated and high-tech industries of the future, there wil be a need for high performance motor drives both in the low-power range and in the high-power range. To meet very straight demands of tracking and regulation in the two quadrants of operation, advanced control technologies are of a considerable interest and need to be developed. In response a dynamics learning control architecture is developed with simultaneous on-line identification and control. the feature of the proposed approach, to efficiently combine the dual task of system identification (learning) and adaptive control of nonlinear motor drives into a single operation is presented. This approach, therefore, not only adapts to uncertainties of the dynamic parameters of the motor drives but also learns about their inherent nonlinearities. In fact, most of the neural networks based adaptive control approaches in use have an identification phase entirely separate from the control phase. Because these approaches separate the identification and control modes, it is not possible to cope with dynamic changes in a controlled process. Extensive simulation studies have been conducted and good performance was observed. The robustness characteristics of neuro-controllers to perform efficiently in a noisy environment is also demonstrated. With this initial success, the principal investigator believes that the proposed approach with the suggested neural structure can be used successfully for the control of high performance motor drives. Two identification and control topologies based on the model reference adaptive control technique are used in this present analysis. No prior knowledge of load dynamics is assumed in either topology while the second topology also assumes no knowledge of the motor parameters.

Performance analysis and prediction in triathlon.

PubMed

Ofoghi, Bahadorreza; Zeleznikow, John; Macmahon, Clare; Rehula, Jan; Dwyer, Dan B

2016-01-01

Performance in triathlon is dependent upon factors that include somatotype, physiological capacity, technical proficiency and race strategy. Given the multidisciplinary nature of triathlon and the interaction between each of the three race components, the identification of target split times that can be used to inform the design of training plans and race pacing strategies is a complex task. The present study uses machine learning techniques to analyse a large database of performances in Olympic distance triathlons (2008-2012). The analysis reveals patterns of performance in five components of triathlon (three race "legs" and two transitions) and the complex relationships between performance in each component and overall performance in a race. The results provide three perspectives on the relationship between performance in each component of triathlon and the final placing in a race. These perspectives allow the identification of target split times that are required to achieve a certain final place in a race and the opportunity to make evidence-based decisions about race tactics in order to optimise performance.

In silico identification and characterization of conserved miRNAs and their target genes in sweet potato (Ipomoea batatas L.) Expressed Sequence Tags (ESTs)

PubMed Central

Dehury, Budheswar; Panda, Debashis; Sahu, Jagajjit; Sahu, Mousumi; Sarma, Kishore; Barooah, Madhumita; Sen, Priyabrata; Modi, Mahendra Kumar

2013-01-01

The endogenous small non-coding micro RNAs (miRNAs), which are typically ~21–24 nt nucleotides, play a crucial role in regulating the intrinsic normal growth of cells and development of the plants as well as in maintaining the integrity of genomes. These small non-coding RNAs function as the universal specificity factors in post-transcriptional gene silencing. Discovering miRNAs, identifying their targets, and further inferring miRNA functions is a routine process to understand normal biological processes of miRNAs and their roles in the development of plants. Comparative genomics based approach using expressed sequence tags (EST) and genome survey sequences (GSS) offer a cost-effective platform for identification and characterization of miRNAs and their target genes in plants. Despite the fact that sweet potato (Ipomoea batatas L.) is an important staple food source for poor small farmers throughout the world, the role of miRNA in various developmental processes remains largely unknown. In this paper, we report the computational identification of miRNAs and their target genes in sweet potato from their ESTs. Using comparative genomics-based approach, 8 potential miRNA candidates belonging to miR168, miR2911, and miR156 families were identified from 23 406 ESTs in sweet potato. A total of 42 target genes were predicted and their probable functions were illustrated. Most of the newly identified miRNAs target transcription factors as well as genes involved in plant growth and development, signal transduction, metabolism, defense, and stress response. The identification of miRNAs and their targets is expected to accelerate the pace of miRNA discovery, leading to an improved understanding of the role of miRNA in development and physiology of sweet potato, as well as stress response. PMID:24067297

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.

Diagnostic performance of dental maturity for identification of skeletal maturation phase.

PubMed

Perinetti, G; Contardo, L; Gabrieli, P; Baccetti, T; Di Lenarda, R

2012-08-01

The objective of this study is to analyse the diagnostic performance of the circumpubertal dental maturation phases for the identification of individual-specific skeletal maturation phases. A total of 354 healthy subjects, 208 females and 146 males (mean age, 11.1 ± 2.4 years; range, 6.8-17.1 years), were enrolled in the study. Dental maturity was assessed through the calcification stages from panoramic radiographs of the mandibular canine, the first and second premolars, and the second molar. Determination of skeletal maturity was according to the cervical vertebra maturation (CVM) method on lateral cephalograms. Diagnostic performances were evaluated according to the dental maturation stages for each tooth for the identification of the CVM stages and growth phases (as pre-pubertal, pubertal, and post-pubertal) using positive likelihood ratios (LHRs). A positive LHR threshold of 10 or more was considered for satisfactory reliability of any dental maturation stage for the identification of any of the CVM stages or growth phases. The positive LHRs were generally less than 2.0, with a few exceptions. These four teeth showed positive LHRs greater than 10 only for the identification of the pre-pubertal growth phase, with values from 10.8 for the second molar (stage E) to 39.3 for the first premolar (stage E). Dental maturation assessment is only useful for diagnosis of the pre-pubertal growth phase, and thus, precise information in relation to the timing of the onset of the growth spurt is not provided by these indices.

Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.

PubMed

Zilbermintz, Leeor; Leonardi, William; Jeong, Sun-Young; Sjodt, Megan; McComb, Ryan; Ho, Chi-Lee C; Retterer, Cary; Gharaibeh, Dima; Zamani, Rouzbeh; Soloveva, Veronica; Bavari, Sina; Levitin, Anastasia; West, Joel; Bradley, Kenneth A; Clubb, Robert T; Cohen, Stanley N; Gupta, Vivek; Martchenko, Mikhail

2015-08-27

A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.

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.

UniDrug-target: a computational tool to identify unique drug targets in pathogenic bacteria.

PubMed

Chanumolu, Sree Krishna; Rout, Chittaranjan; Chauhan, Rajinder S

2012-01-01

Targeting conserved proteins of bacteria through antibacterial medications has resulted in both the development of resistant strains and changes to human health by destroying beneficial microbes which eventually become breeding grounds for the evolution of resistances. Despite the availability of more than 800 genomes sequences, 430 pathways, 4743 enzymes, 9257 metabolic reactions and protein (three-dimensional) 3D structures in bacteria, no pathogen-specific computational drug target identification tool has been developed. A web server, UniDrug-Target, which combines bacterial biological information and computational methods to stringently identify pathogen-specific proteins as drug targets, has been designed. Besides predicting pathogen-specific proteins essentiality, chokepoint property, etc., three new algorithms were developed and implemented by using protein sequences, domains, structures, and metabolic reactions for construction of partial metabolic networks (PMNs), determination of conservation in critical residues, and variation analysis of residues forming similar cavities in proteins sequences. First, PMNs are constructed to determine the extent of disturbances in metabolite production by targeting a protein as drug target. Conservation of pathogen-specific protein's critical residues involved in cavity formation and biological function determined at domain-level with low-matching sequences. Last, variation analysis of residues forming similar cavities in proteins sequences from pathogenic versus non-pathogenic bacteria and humans is performed. The server is capable of predicting drug targets for any sequenced pathogenic bacteria having fasta sequences and annotated information. The utility of UniDrug-Target server was demonstrated for Mycobacterium tuberculosis (H37Rv). The UniDrug-Target identified 265 mycobacteria pathogen-specific proteins, including 17 essential proteins which can be potential drug targets. UniDrug-Target is expected to accelerate

Identification of a pharmacological target for genioglossus reactivation throughout sleep.

PubMed

Grace, Kevin P; Hughes, Stuart W; Horner, Richard L

2014-01-01

Obstructive sleep apnea (OSA) is a significant public health problem caused by repeated episodes of upper airway closure that occur only during sleep. Attempts to treat OSA pharmacologically have been unsuccessful because there has not been identification of a target operating at cranial motor nuclei, blockade of which can reactivate pharyngeal muscle activity throughout sleep. Increasing potassium conductance is a common mechanism by which state-dependent neuromodulators reduce motoneuron excitability. Therefore, we aimed to determine if potassium channel blockade is an effective strategy to reactivate the pharyngeal musculature throughout sleep. In rats chronically instrumented for recording sleep-wake states and respiratory motor activities, we locally microperfused pharmacological agents into the hypoglossal motor pool to modulate potassium channels of three major classes: inwardly rectifying, two-pore domain, and voltage-gated. Microperfusion of the inwardly rectifying potassium channel blocker, barium, as well as the voltage-gated potassium channel blockers, tetraethylammonium and 4-aminopyridine, increased tonic and respiratory-related genioglossus activities throughout nonrapid eye movement (non-REM) and rapid eye movement (REM) sleep to 133-300% of levels present during baseline wakefulness. In contrast, microperfusion of methanandamide (TWIK-related acid-sensitive potassium [TASK] channel blocker/cannabinoid receptor agonist) activated genioglossus in wakefulness but not in sleep. These findings establish proof-of-principle that targeted blockade of certain potassium channels at the hypoglossal motor pool is an effective strategy for reversing upper airway hypotonia and causing sustained reactivation of genioglossus throughout nonrapid eye movement and rapid eye movement sleep. These findings identify an important new direction for translational approaches to the pharmacological treatment of obstructive sleep apnea.

Goodbye or Identify: Detrimental Effects of Downsizing on Identification and Survivor Performance

PubMed Central

van Dick, Rolf; Drzensky, Frank; Heinz, Matthias

2016-01-01

Research shows that after layoffs, employees often report decreased commitment and performance which has been coined the survivor syndrome. However, the mechanisms underlying this effect remain underexplored. The purpose of the paper is to show that reduced organizational identification can serve as an explanation for the survivor syndrome. We conducted a laboratory experiment, in which participants work as a group of employees for another participant who acts as employer. In the course of the experiment, the employer decides whether one of his or her employees should be laid off or not. Mediation analysis supports a social identity-based explanation for the emergence of the survivor syndrome: downsizing causes lower identification with the employer which in turn relates to lower performance of employees. PMID:27252674

Goodbye or Identify: Detrimental Effects of Downsizing on Identification and Survivor Performance.

PubMed

van Dick, Rolf; Drzensky, Frank; Heinz, Matthias

2016-01-01

Research shows that after layoffs, employees often report decreased commitment and performance which has been coined the survivor syndrome. However, the mechanisms underlying this effect remain underexplored. The purpose of the paper is to show that reduced organizational identification can serve as an explanation for the survivor syndrome. We conducted a laboratory experiment, in which participants work as a group of employees for another participant who acts as employer. In the course of the experiment, the employer decides whether one of his or her employees should be laid off or not. Mediation analysis supports a social identity-based explanation for the emergence of the survivor syndrome: downsizing causes lower identification with the employer which in turn relates to lower performance of employees.

Optical Quality and Threshold Target Identification and Military Target Task Performance after Advanced Keratorefractive Surgery

DTIC Science & Technology

2013-05-01

and Sensors Directorate. • Study participants and physicians select treatment: PRK or LASIK . WFG vs . WFO treatment modality is randomized. The...to undergo wavefront-guided (WFG) photorefractive keratectomy ( PRK ), WFG laser in situ keratomileusis ( LASIK ), wavefront optimized (WFO) PRK or WFO...TERMS Military, Refractive Surgery, PRK , LASIK , Night Vision, Wavefront Optimized, Wavefront Guided, Visual Performance, Quality of Vision, Outcomes

Identification of small molecule compounds targeting the interaction of HIV-1 Vif and human APOBEC3G by virtual screening and biological evaluation.

PubMed

Ma, Ling; Zhang, Zhixin; Liu, Zhenlong; Pan, Qinghua; Wang, Jing; Li, Xiaoyu; Guo, Fei; Liang, Chen; Hu, Laixing; Zhou, Jinming; Cen, Shan

2018-05-23

Human APOBEC3G (hA3G) is a restriction factor that inhibits human immunodeficiency 1 virus (HIV-1) replication. The virally encoded protein Vif binds to hA3G and induces its degradation, thereby counteracting the antiviral activity of hA3G. Vif-mediated hA3G degradation clearly represents a potential target for anti-HIV drug development. Herein, we have performed virtual screening to discover small molecule inhibitors that target the binding interface of the Vif/hA3G complex. Subsequent biochemical studies have led to the identification of a small molecule inhibitor, IMB-301 that binds to hA3G, interrupts the hA3G-Vif interaction and inhibits Vif-mediated degradation of hA3G. As a result, IMB-301 strongly inhibits HIV-1 replication in a hA3G-dependent manner. Our study further demonstrates the feasibility of inhibiting HIV replication by abrogating the Vif-hA3G interaction with small molecules.

Identification of highly effective target genes for RNAi-mediated control of emerald ash borer, Agrilus planipennis.

PubMed

Rodrigues, Thais B; Duan, Jian J; Palli, Subba R; Rieske, Lynne K

2018-03-22

Recent study has shown that RNA interference (RNAi) is efficient in emerald ash borer (EAB), Agrilus planipennis, and that ingestion of double-stranded RNA (dsRNA) targeting specific genes causes gene silencing and mortality in neonates. Here, we report on the identification of highly effective target genes for RNAi-mediated control of EAB. We screened 13 candidate genes in neonate larvae and selected the most effective target genes for further investigation, including their effect on EAB adults and on a non-target organism, Tribolium castaneum. The two most efficient target genes selected, hsp (heat shock 70-kDa protein cognate 3) and shi (shibire), caused up to 90% mortality of larvae and adults. In EAB eggs, larvae, and adults, the hsp is expressed at higher levels when compared to that of shi. Ingestion of dsHSP and dsSHI caused mortality in both neonate larvae and adults. Administration of a mixture of both dsRNAs worked better than either dsRNA by itself. In contrast, injection of EAB.dsHSP and EAB.dsSHI did not cause mortality in T. castaneum. Thus, the two genes identified cause high mortality in the EAB with no apparent phenotype effects in a non-target organism, the red flour beetle, and could be used in RNAi-mediated control of this invasive pest.

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.

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.

Identification of testis-specific male contraceptive targets: insights from transcriptional profiling of the cycle of the rat seminiferous epithelium and purified testicular cells.

PubMed

Johnston, Daniel S; Jelinsky, Scott A; Zhi, Yu; Finger, Joshua N; Kopf, Gregory S; Wright, William W

2007-12-01

In an effort to identify novel targets for the development of nonhormonal male contraceptives, genome-wide transcriptional profiling of the rat testis was performed. Specifically, enzymatically purified spermatogonia plus early spermatocyctes, pachytene spermatocytes, round spermatids, and Sertoli cells was analyzed along with microdissected rat seminiferous tubules at stages I, II-III, IV-V, VI, VIIa,b, VIIc,d, VIII, IX- XI, XII, XIII-XIV of the cycle of the seminiferous epithelium using RAE 230_2.0 microarrays. The combined analysis of these studies identified 16,971 expressed probe sets on the array. How these expression data, combined with additional bioinformatic data analysis and quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) analysis, led to the identification of 58 genes that have 1000-fold higher expression transcriptionally in the testis when compared to over 20 other nonreproductive tissues is described. The products of these genes may play important roles in testicular and/or sperm function, and further investigation on their utility as nonhormonal contraceptive targets is warranted. Moreover, these microarray data have been used to expedite the identification of a mutation in RIKEN cDNA 2410004F06 gene as likely being responsible for spermatogenic failure in a line of infertile mice generated by N-ethyl-N-nitrosourea (ENU) mutagenesis. The microarray data and the qRT-PCR data described are available in the Mammalian Reproductive Genetics database (http://mrg.genetics.washington.edu/).

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

Probability of identification: a statistical model for the validation of qualitative botanical identification methods.

PubMed

LaBudde, Robert A; Harnly, James M

2012-01-01

A qualitative botanical identification method (BIM) is an analytical procedure that 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) material, or whether it contains excessive nontarget (undesirable) material. The report describes the development and validation of studies for a BIM based on the proportion of replicates identified, or probability of identification (POI), as the basic observed statistic. The statistical procedures proposed for data analysis follow closely those of the probability of detection, and harmonize the statistical concepts and parameters between quantitative and qualitative method validation. Use of POI statistics also harmonizes statistical concepts for botanical, microbiological, toxin, and other analyte identification methods that produce binary results. The POI statistical model provides a tool for graphical representation of response curves for qualitative methods, reporting of descriptive statistics, and application of performance requirements. Single collaborator and multicollaborative study examples are given.

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.

Performance evaluation of three automated identification systems in detecting carbapenem-resistant Enterobacteriaceae.

PubMed

He, Qingwen; Chen, Weiyuan; Huang, Liya; Lin, Qili; Zhang, Jingling; Liu, Rui; Li, Bin

2016-06-21

Carbapenem-resistant Enterobacteriaceae (CRE) is prevalent around the world. Rapid and accurate detection of CRE is urgently needed to provide effective treatment. Automated identification systems have been widely used in clinical microbiology laboratories for rapid and high-efficient identification of pathogenic bacteria. However, critical evaluation and comparison are needed to determine the specificity and accuracy of different systems. The aim of this study was to evaluate the performance of three commonly used automated identification systems on the detection of CRE. A total of 81 non-repetitive clinical CRE isolates were collected from August 2011 to August 2012 in a Chinese university hospital, and all the isolates were confirmed to be resistant to carbapenems by the agar dilution method. The potential presence of carbapenemase genotypes of the 81 isolates was detected by PCR and sequencing. Using 81 clinical CRE isolates, we evaluated and compared the performance of three automated identification systems, MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact, which are commonly used in China. To identify CRE, the comparator methodology was agar dilution method, while the PCR and sequencing was the comparator one to identify CPE. PCR and sequencing analysis showed that 48 of the 81 CRE isolates carried carbapenemase genes, including 23 (28.4 %) IMP-4, 14 (17.3 %) IMP-8, 5 (6.2 %) NDM-1, and 8 (9.9 %) KPC-2. Notably, one Klebsiella pneumoniae isolate produced both IMP-4 and NDM-1. One Klebsiella oxytoca isolate produced both KPC-2 and IMP-8. Of the 81 clinical CRE isolates, 56 (69.1 %), 33 (40.7 %) and 77 (95.1 %) were identified as CRE by MicroScan WalkAway 96 Plus, Phoenix 100, and Vitek 2 Compact, respectively. The sensitivities/specificities of MicroScan WalkAway, Phoenix 100 and Vitek 2 were 93.8/42.4 %, 54.2/66.7 %, and 75.0/36.4 %, respectively. The MicroScan WalkAway and Viteck2 systems are more reliable in clinical identification of

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.

Domain identification moderates the effect of positive stereotypes on Chinese American women's math performance.

PubMed

Saad, Carmel S; Meyer, Oanh L; Dhindsa, Manveen; Zane, Nolan

2015-01-01

We examined whether an individual difference factor, math domain identification, moderated performance following positive stereotype activation. We hypothesized that positive stereotype activation would improve performance for those more math identified (compared to a control condition), but would hinder performance for those less math identified. We examined 116 Chinese American women (mean age = 19 years). Participants were assigned to the positive stereotype activation condition or to the control condition before completing a math test. Positive stereotype activation led more math identified participants to perform significantly better than the control condition, whereas it led less math identified participants to perform significantly worse than the control condition. Domain identification moderates the effect of positive stereotype activation. Educators should consider how testing situations are constructed, especially when test takers do not identify highly with the domain. (PsycINFO Database Record (c) 2015 APA, all rights reserved).

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

PubMed

Prakash, Pravin; Rajakani, Raja; Gupta, Vikrant

2016-04-01

MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 19-24 nucleotides (nt) in length and considered as potent regulators of gene expression at transcriptional and post-transcriptional levels. Here we report the identification and characterization of 15 conserved miRNAs belonging to 13 families from Rauvolfia serpentina through in silico analysis of available nucleotide dataset. The identified mature R. serpentina miRNAs (rse-miRNAs) ranged between 20 and 22nt in length, and the average minimal folding free energy index (MFEI) value of rse-miRNA precursor sequences was found to be -0.815 kcal/mol. Using the identified rse-miRNAs as query, their potential targets were predicted in R. serpentina and other plant species. Gene Ontology (GO) annotation showed that predicted targets of rse-miRNAs include transcription factors as well as genes involved in diverse biological processes such as primary and secondary metabolism, stress response, disease resistance, growth, and development. Few rse-miRNAs were predicted to target genes of pharmaceutically important secondary metabolic pathways such as alkaloids and anthocyanin biosynthesis. Phylogenetic analysis showed the evolutionary relationship of rse-miRNAs and their precursor sequences to homologous pre-miRNA sequences from other plant species. The findings under present study besides giving first hand information about R. serpentina miRNAs and their targets, also contributes towards the better understanding of miRNA-mediated gene regulatory processes in plants. Copyright © 2015 Elsevier Ltd. All rights reserved.

Genomic identification of potential targets unique to Candida albicans for the discovery of antifungal agents.

PubMed

Tripathi, Himanshu; Luqman, Suaib; Meena, Abha; Khan, Feroz

2014-01-01

Despite of modern antifungal therapy, the mortality rates of invasive infection with human fungal pathogen Candida albicans are up to 40%. Studies suggest that drug resistance in the three most common species of human fungal pathogens viz., C. albicans, Aspergillus fumigatus (causing mortality rate up to 90%) and Cryptococcus neoformans (causing mortality rate up to 70%) is due to mutations in the target enzymes or high expression of drug transporter genes. Drug resistance in human fungal pathogens has led to an imperative need for the identification of new targets unique to fungal pathogens. In the present study, we have used a comparative genomics approach to find out potential target proteins unique to C. albicans, an opportunistic fungus responsible for severe infection in immune-compromised human. Interestingly, many target proteins of existing antifungal agents showed orthologs in human cells. To identify unique proteins, we have compared proteome of C. albicans [SC5314] i.e., 14,633 total proteins retrieved from the RefSeq database of NCBI, USA with proteome of human and non-pathogenic yeast Saccharomyces cerevisiae. Results showed that 4,568 proteins were identified unique to C. albicans as compared to those of human and later when these unique proteins were compared with S. cerevisiae proteome, finally 2,161 proteins were identified as unique proteins and after removing repeats total 1,618 unique proteins (42 functionally known, 1,566 hypothetical and 10 unknown) were selected as potential antifungal drug targets unique to C. albicans.

The Nike KrF laser facility: Performance and initial target experiments

NASA Astrophysics Data System (ADS)

Obenschain, S. P.; Bodner, S. E.; Colombant, D.; Gerber, K.; Lehmberg, R. H.; McLean, E. A.; Mostovych, A. N.; Pronko, M. S.; Pawley, C. J.; Schmitt, A. J.; Sethian, J. D.; Serlin, V.; Stamper, J. A.; Sullivan, C. A.; Dahlburg, J. P.; Gardner, J. H.; Chan, Y.; Deniz, A. V.; Hardgrove, J.; Lehecka, T.; Klapisch, M.

1996-05-01

Krypton-fluoride (KrF) lasers are of interest to laser fusion because they have both the large bandwidth capability (≳THz) desired for rapid beam smoothing and the short laser wavelength (1/4 μm) needed for good laser-target coupling. Nike is a recently completed 56-beam KrF laser and target facility at the Naval Research Laboratory. Because of its bandwidth of 1 THz FWHM (full width at half-maximum), Nike produces more uniform focal distributions than any other high-energy ultraviolet laser. Nike was designed to study the hydrodynamic instability of ablatively accelerated planar targets. First results show that Nike has spatially uniform ablation pressures (Δp/p<2%). Targets have been accelerated for distances sufficient to study hydrodynamic instability while maintaining good planarity. In this review we present the performance of the Nike laser in producing uniform illumination, and its performance in correspondingly uniform acceleration of targets.

Performing target specific band reduction using artificial neural networks and assessment of its efficacy using various target detection algorithms

NASA Astrophysics Data System (ADS)

Yadav, Deepti; Arora, M. K.; Tiwari, K. C.; Ghosh, J. K.

2016-04-01

Hyperspectral imaging is a powerful tool in the field of remote sensing and has been used for many applications like mineral detection, detection of landmines, target detection etc. Major issues in target detection using HSI are spectral variability, noise, small size of the target, huge data dimensions, high computation cost, complex backgrounds etc. Many of the popular detection algorithms do not work for difficult targets like small, camouflaged etc. and may result in high false alarms. Thus, target/background discrimination is a key issue and therefore analyzing target's behaviour in realistic environments is crucial for the accurate interpretation of hyperspectral imagery. Use of standard libraries for studying target's spectral behaviour has limitation that targets are measured in different environmental conditions than application. This study uses the spectral data of the same target which is used during collection of the HSI image. This paper analyze spectrums of targets in a way that each target can be spectrally distinguished from a mixture of spectral data. Artificial neural network (ANN) has been used to identify the spectral range for reducing data and further its efficacy for improving target detection is verified. The results of ANN proposes discriminating band range for targets; these ranges were further used to perform target detection using four popular spectral matching target detection algorithm. Further, the results of algorithms were analyzed using ROC curves to evaluate the effectiveness of the ranges suggested by ANN over full spectrum for detection of desired targets. In addition, comparative assessment of algorithms is also performed using ROC.

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.

Performance study of LMS based adaptive algorithms for unknown system identification

NASA Astrophysics Data System (ADS)

Javed, Shazia; Ahmad, Noor Atinah

2014-07-01

Adaptive filtering techniques have gained much popularity in the modeling of unknown system identification problem. These techniques can be classified as either iterative or direct. Iterative techniques include stochastic descent method and its improved versions in affine space. In this paper we present a comparative study of the least mean square (LMS) algorithm and some improved versions of LMS, more precisely the normalized LMS (NLMS), LMS-Newton, transform domain LMS (TDLMS) and affine projection algorithm (APA). The performance evaluation of these algorithms is carried out using adaptive system identification (ASI) model with random input signals, in which the unknown (measured) signal is assumed to be contaminated by output noise. Simulation results are recorded to compare the performance in terms of convergence speed, robustness, misalignment, and their sensitivity to the spectral properties of input signals. Main objective of this comparative study is to observe the effects of fast convergence rate of improved versions of LMS algorithms on their robustness and misalignment.

Performance study of LMS based adaptive algorithms for unknown system identification

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

Javed, Shazia; Ahmad, Noor Atinah

Adaptive filtering techniques have gained much popularity in the modeling of unknown system identification problem. These techniques can be classified as either iterative or direct. Iterative techniques include stochastic descent method and its improved versions in affine space. In this paper we present a comparative study of the least mean square (LMS) algorithm and some improved versions of LMS, more precisely the normalized LMS (NLMS), LMS-Newton, transform domain LMS (TDLMS) and affine projection algorithm (APA). The performance evaluation of these algorithms is carried out using adaptive system identification (ASI) model with random input signals, in which the unknown (measured) signalmore » is assumed to be contaminated by output noise. Simulation results are recorded to compare the performance in terms of convergence speed, robustness, misalignment, and their sensitivity to the spectral properties of input signals. Main objective of this comparative study is to observe the effects of fast convergence rate of improved versions of LMS algorithms on their robustness and misalignment.« less

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.

Identification of plant glutaredoxin targets.

PubMed

Rouhier, Nicolas; Villarejo, Arsenio; Srivastava, Manoj; Gelhaye, Eric; Keech, Olivier; Droux, Michel; Finkemeier, Iris; Samuelsson, Göran; Dietz, Karl Josef; Jacquot, Jean-Pierre; Wingsle, Gunnar

2005-01-01

Glutaredoxins (Grxs) are small ubiquitous proteins of the thioredoxin (Trx) family, which catalyze dithiol-disulfide exchange reactions or reduce protein-mixed glutathione disulfides. In plants, several Trx-interacting proteins have been isolated from different compartments, whereas very few Grx-interacting proteins are known. We describe here the determination of Grx target proteins using a mutated poplar Grx, various tissular and subcellular plant extracts, and liquid chromatography coupled to tandem mass spectrometry detection. We have identified 94 putative targets, involved in many processes, including oxidative stress response [peroxiredoxins (Prxs), ascorbate peroxidase, catalase], nitrogen, sulfur, and carbon metabolisms (methionine synthase, alanine aminotransferase, phosphoglycerate kinase), translation (elongation factors E and Tu), or protein folding (heat shock protein 70). Some of these proteins were previously found to interact with Trx or to be glutathiolated in other organisms, but others could be more specific partners of Grx. To substantiate further these data, Grx was shown to support catalysis of the stroma beta-type carbonic anhydrase and Prx IIF of Arabidopsis thaliana, but not of poplar 2-Cys Prx. Overall, these data suggest that the interaction could occur randomly either with exposed cysteinyl disulfide bonds formed within or between target proteins or with mixed disulfides between a protein thiol and glutathione.

Diagnostic performance of combined canine and second molar maturity for identification of growth phase.

PubMed

Perinetti, Giuseppe; Di Lenarda, Roberto; Contardo, Luca

2013-05-20

The objective of this research is to analyze the diagnostic performance of the circumpubertal dental maturation stages of the mandibular canine and second molar, as individual teeth and in combination, for the identification of growth phase. A total of 300 healthy subjects, 192 females and 108 males, were enrolled in the study (mean age, 11.4±2.4 years; range, 6.8 to 17.1 years). Dental maturity was assessed through the calcification stages from panoramic radiographs of the mandibular canine and second molar. Determination of growth phase (as pre-pubertal, pubertal, and post-pubertal) was carried out according to the cervical vertebral maturation method. The diagnostic performances of the dental maturation stages, as both individual teeth and in combination, for the identification of the growth phase were evaluated using positive likelihood ratios (LHRs), with a threshold of ≥10 for satisfactory performance. For the individual dental maturation stages, most of these positive LHRs were ≤1.6, with values≥10 seen only for the identification of the pre-pubertal growth phase for canine stage F and second molar stages D and E, and for the post-pubertal growth phase for second molar stage H. All of the combined dental maturation stages yielded positive LHRs up to 2.6. Dental maturation of either individual or combined teeth has little role in the identification of the pubertal growth spurt and should not be used to assess timing for treatments that are required to be performed at this growth phase.

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.

The eccentricity effect: target eccentricity affects performance on conjunction searches.

PubMed

Carrasco, M; Evert, D L; Chang, I; Katz, S M

1995-11-01

The serial pattern found for conjunction visual-search tasks has been attributed to covert attentional shifts, even though the possible contributions of target location have not been considered. To investigate the effect of target location on orientation x color conjunction searches, the target's duration and its position in the display were manipulated. The display was present either until observers responded (Experiment 1), for 104 msec (Experiment 2), or for 62 msec (Experiment 3). Target eccentricity critically affected performance: A pronounced eccentricity effect was very similar for all three experiments; as eccentricity increased, reaction times and errors increased gradually. Furthermore, the set-size effect became more pronounced as target eccentricity increased, and the extent of the eccentricity effect increased for larger set sizes. In addition, according to stepwise regressions, target eccentricity as well as its interaction with set size were good predictors of performance. We suggest that these findings could be explained by spatial-resolution and lateral-inhibition factors. The serial self-terminating hypothesis for orientation x color conjunction searches was evaluated and rejected. We compared the eccentricity effect as well as the extent of the orientation asymmetry in these three conjunction experiments with those found in feature experiments (Carrasco & Katz, 1992). The roles of eye movements, spatial resolution, and covert attention in the eccentricity effect, as well as their implications, are discussed.

Culture-Independent Identification of Periodontitis-Associated Porphyromonas and Tannerella Populations by Targeted Molecular Analysis

PubMed Central

de Lillo, A.; Booth, V.; Kyriacou, L.; Weightman, A. J.; Wade, W. G.

2004-01-01

Periodontitis is the commonest bacterial disease of humans and is the major cause of adult tooth loss. About half of the oral microflora is unculturable; and 16S rRNA PCR, cloning, and sequencing techniques have demonstrated the high level of species richness of the oral microflora. In the present study, a PCR primer set specific for the genera Porphyromonas and Tannerella was designed and used to analyze the bacterial populations in subgingival plaque samples from inflamed shallow and deep sites in subjects with periodontitis and shallow sites in age- and sex-matched controls. A total of 308 clones were sequenced and found to belong to one of six Porphyromonas or Tannerella species or phylotypes, one of which, Porphyromonas P3, was novel. Tannerella forsythensis was found in significantly higher proportions in patients than in controls. Porphyromonas catoniae and Tannerella phylotype BU063 appeared to be associated with shallow sites. Targeted culture-independent molecular ecology studies have a valuable role to play in the identification of bacterial targets for further investigations of the pathogenesis of bacterial infections. PMID:15583276

Visual performance on detection tasks with double-targets of the same and different difficulty.

PubMed

Chan, Alan H S; Courtney, Alan J; Ma, C W

2002-10-20

This paper reports a study of measurement of horizontal visual sensitivity limits for 16 subjects in single-target and double-targets detection tasks. Two phases of tests were conducted in the double-targets task; targets of the same difficulty were tested in phase one while targets of different difficulty were tested in phase two. The range of sensitivity for the double-targets test was found to be smaller than that for single-target in both the same and different target difficulty cases. The presence of another target was found to affect performance to a marked degree. Interference effect of the difficult target on detection of the easy one was greater than that of the easy one on the detection of the difficult one. Performance decrement was noted when correct percentage detection was plotted against eccentricity of target in both the single-target and double-targets tests. Nevertheless, the non-significant correlation found between the performance for the two tasks demonstrated that it was impossible to predict quantitatively ability for detection of double targets from the data for single targets. This indicated probable problems in generalizing data for single target visual lobes to those for multiple targets. Also lobe area values obtained from measurements using a single-target task cannot be applied in a mathematical model for situations with multiple occurrences of targets.

Identification of Novel Pax8 Targets in FRTL-5 Thyroid Cells by Gene Silencing and Expression Microarray Analysis

PubMed Central

Di Palma, Tina; Conti, Anna; de Cristofaro, Tiziana; Scala, Serena; Nitsch, Lucio; Zannini, Mariastella

2011-01-01

Background The differentiation program of thyroid follicular cells (TFCs), by far the most abundant cell population of the thyroid gland, relies on the interplay between sequence-specific transcription factors and transcriptional coregulators with the basal transcriptional machinery of the cell. However, the molecular mechanisms leading to the fully differentiated thyrocyte are still the object of intense study. The transcription factor Pax8, a member of the Paired-box gene family, has been demonstrated to be a critical regulator required for proper development and differentiation of thyroid follicular cells. Despite being Pax8 well-characterized with respect to its role in regulating genes involved in thyroid differentiation, genomics approaches aiming at the identification of additional Pax8 targets are lacking and the biological pathways controlled by this transcription factor are largely unknown. Methodology/Principal Findings To identify unique downstream targets of Pax8, we investigated the genome-wide effect of Pax8 silencing comparing the transcriptome of silenced versus normal differentiated FRTL-5 thyroid cells. In total, 2815 genes were found modulated 72 h after Pax8 RNAi, induced or repressed. Genes previously reported to be regulated by Pax8 in FRTL-5 cells were confirmed. In addition, novel targets genes involved in functional processes such as DNA replication, anion transport, kinase activity, apoptosis and cellular processes were newly identified. Transcriptome analysis highlighted that Pax8 is a key molecule for thyroid morphogenesis and differentiation. Conclusions/Significance This is the first large-scale study aimed at the identification of new genes regulated by Pax8, a master regulator of thyroid development and differentiation. The biological pathways and target genes controlled by Pax8 will have considerable importance to understand thyroid disease progression as well as to set up novel therapeutic strategies. PMID:21966443

Identification of a novel LMF1 nonsense mutation responsible for severe hypertriglyceridemia by targeted next-generation sequencing.

PubMed

Cefalù, Angelo B; Spina, Rossella; Noto, Davide; Ingrassia, Valeria; Valenti, Vincenza; Giammanco, Antonina; Fayer, Francesca; Misiano, Gabriella; Cocorullo, Gianfranco; Scrimali, Chiara; Palesano, Ornella; Altieri, Grazia I; Ganci, Antonina; Barbagallo, Carlo M; Averna, Maurizio R

Severe hypertriglyceridemia (HTG) may result from mutations in genes affecting the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. The aim of this study was to develop a targeted next-generation sequencing panel for the molecular diagnosis of disorders characterized by severe HTG. We developed a targeted customized panel for next-generation sequencing Ion Torrent Personal Genome Machine to capture the coding exons and intron/exon boundaries of 18 genes affecting the main pathways of TG synthesis and metabolism. We sequenced 11 samples of patients with severe HTG (TG>885 mg/dL-10 mmol/L): 4 positive controls in whom pathogenic mutations had previously been identified by Sanger sequencing and 7 patients in whom the molecular defect was still unknown. The customized panel was accurate, and it allowed to confirm genetic variants previously identified in all positive controls with primary severe HTG. Only 1 patient of 7 with HTG was found to be carrier of a homozygous pathogenic mutation of the third novel mutation of LMF1 gene (c.1380C>G-p.Y460X). The clinical and molecular familial cascade screening allowed the identification of 2 additional affected siblings and 7 heterozygous carriers of the mutation. We showed that our targeted resequencing approach for genetic diagnosis of severe HTG appears to be accurate, less time consuming, and more economical compared with traditional Sanger resequencing. The identification of pathogenic mutations in candidate genes remains challenging and clinical resequencing should mainly intended for patients with strong clinical criteria for monogenic severe HTG. Copyright © 2017 National Lipid Association. Published by Elsevier Inc. All rights reserved.

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

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.

Uncooperative target-in-the-loop performance with backscattered speckle-field effects

NASA Astrophysics Data System (ADS)

Kansky, Jan E.; Murphy, Daniel V.

2007-09-01

Systems utilizing target-in-the-loop (TIL) techniques for adaptive optics phase compensation rely on a metric sensor to perform a hill climbing algorithm that maximizes the far-field Strehl ratio. In uncooperative TIL, the metric signal is derived from the light backscattered from a target. In cases where the target is illuminated with a laser with suffciently long coherence length, the potential exists for the validity of the metric sensor to be compromised by speckle-field effects. We report experimental results from a scaled laboratory designed to evaluate TIL performance in atmospheric turbulence and thermal blooming conditions where the metric sensors are influenced by varying degrees of backscatter speckle. We compare performance of several TIL configurations and metrics for cases with static speckle, and for cases with speckle fluctuations within the frequency range that the TIL system operates. The roles of metric sensor filtering and system bandwidth are discussed.

Simultaneous screening of targeted and non-targeted contaminants using an LC-QTOF-MS system and automated MS/MS library searching.

PubMed

Herrera-Lopez, S; Hernando, M D; García-Calvo, E; Fernández-Alba, A R; Ulaszewska, M M

2014-09-01

Simultaneous high-resolution full-scan and tandem mass spectrometry (MS/MS) analysis using time of flight mass spectrometry brings an answer for increasing demand of retrospective and non-targeted data analysis. Such analysis combined with spectral library searching is a promising tool for targeted and untargeted screening of small molecules. Despite considerable extension of the panel of compounds of tandem mass spectral libraries, the heterogeneity of spectral data poses a major challenge against the effective usage of spectral libraries. Performance evaluation of available LC-MS/MS libraries will significantly increase credibility in the search results. The present work was aimed to evaluate fluctuation of MS/MS pattern, in the peak intensities distribution together with mass accuracy measurements, and in consequence, performance compliant with ion ratio and mass error criteria as principles in identification processes for targeted and untargeted contaminants at trace levels. Matrix effect and ultra-trace levels of concentration (from 50 ng l(-1) to 1000 ng l(-1) were evaluated as potential source of inaccuracy in the performance of spectral matching. Matrix-matched samples and real samples were screened for proof of applicability. By manual review of data and application of ion ratio and ppm error criteria, false negatives were obtained; this number diminished when in-house library was used, while with on-line MS/MS databases 100% of positive samples were found. In our experience, intensity of peaks across spectra was highly correlated to the concentration effect and matrix complexity. In turn, analysis of spectra acquired at trace concentrations and in different matrices results in better performance in providing correct and reliable identification. Copyright © 2014 John Wiley & Sons, Ltd.

Experiment research on infrared targets signature in mid and long IR spectral bands

NASA Astrophysics Data System (ADS)

Wang, Chensheng; Hong, Pu; Lei, Bo; Yue, Song; Zhang, Zhijie; Ren, Tingting

2013-09-01

Since the infrared imaging system has played a significant role in the military self-defense system and fire control system, the radiation signature of IR target becomes an important topic in IR imaging application technology. IR target signature can be applied in target identification, especially for small and dim targets, as well as the target IR thermal design. To research and analyze the targets IR signature systematically, a practical and experimental project is processed under different backgrounds and conditions. An infrared radiation acquisition system based on a MWIR cooled thermal imager and a LWIR cooled thermal imager is developed to capture the digital infrared images. Furthermore, some instruments are introduced to provide other parameters. According to the original image data and the related parameters in a certain scene, the IR signature of interested target scene can be calculated. Different background and targets are measured with this approach, and a comparison experiment analysis shall be presented in this paper as an example. This practical experiment has proved the validation of this research work, and it is useful in detection performance evaluation and further target identification research.

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.

Cy5 maleimide labelling for sensitive detection of free thiols in native protein extracts: identification of seed proteins targeted by barley thioredoxin h isoforms.

PubMed Central

Maeda, Kenji; Finnie, Christine; Svensson, Birte

2004-01-01

Barley thioredoxin h isoforms HvTrxh1 and HvTrxh2 differ in temporal and spatial distribution and in kinetic properties. Target proteins of HvTrxh1 and HvTrxh2 were identified in mature seeds and in seeds after 72 h of germination. Improvement of the established method for identification of thioredoxin-targeted proteins based on two-dimensional electrophoresis and fluorescence labelling of thiol groups was achieved by application of a highly sensitive Cy5 maleimide dye and large-format two-dimensional gels, resulting in a 10-fold increase in the observed number of labelled protein spots. The technique also provided information about accessible thiol groups in the proteins identified in the barley seed proteome. In total, 16 different putative target proteins were identified from 26 spots using tryptic in-gel digestion, matrix-assisted laser-desorption ionization-time-of-flight MS and database search. HvTrxh1 and HvTrxh2 were shown to have similar target specificity. Barley alpha-amylase/subtilisin inhibitor, previously demonstrated to be reduced by both HvTrxh1 and HvTrxh2, was among the identified target proteins, confirming the suitability of the method. Several alpha-amylase/trypsin inhibitors, some of which are already known as target proteins of thioredoxin h, and cyclophilin known as a target protein of m-type thioredoxin were also identified. Lipid transfer protein, embryospecific protein, three chitinase isoenzymes, a single-domain glyoxalase-like protein and superoxide dismutase were novel identifications of putative target proteins, suggesting new physiological roles of thioredoxin h in barley seeds. PMID:14636158

Missing the Boat--Impact of Just Missing Identification as a High-Performing School

ERIC Educational Resources Information Center

Weiner, Jennie; Donaldson, Morgaen; Dougherty, Shaun M.

2017-01-01

This study capitalizes on the performance identification system under the No Child Left Behind waivers to estimate the school-level impact of just missing formal state recognition as a high-performing school. Using a fuzzy regression-discontinuity design and data from the early years of waiver implementation in Rhode Island, we find that, when…

eap Gene as novel target for specific identification of Staphylococcus aureus.

PubMed

Hussain, Muzaffar; von Eiff, Christof; Sinha, Bhanu; Joost, Insa; Herrmann, Mathias; Peters, Georg; Becker, Karsten

2008-02-01

The cell surface-associated extracellular adherence protein (Eap) mediates adherence of Staphylococcus aureus to host extracellular matrix components and inhibits inflammation, wound healing, and angiogenesis. A well-characterized collection of S. aureus and non-S. aureus staphylococcal isolates (n = 813) was tested for the presence of the Eap-encoding gene (eap) by PCR to investigate the use of the eap gene as a specific diagnostic tool for identification of S. aureus. Whereas all 597 S. aureus isolates were eap positive, this gene was not detectable in 216 non-S. aureus staphylococcal isolates comprising 47 different species and subspecies of coagulase-negative staphylococci and non-S. aureus coagulase-positive or coagulase-variable staphylococci. Furthermore, non-S. aureus isolates did not express Eap homologs, as verified on the transcriptional and protein levels. Based on these data, the sensitivity and specificity of the newly developed PCR targeting the eap gene were both 100%. Thus, the unique occurrence of Eap in S. aureus offers a promising tool particularly suitable for molecular diagnostics of this pathogen.

Local structure preserving sparse coding for infrared target recognition

PubMed Central

Han, Jing; Yue, Jiang; Zhang, Yi; Bai, Lianfa

2017-01-01

Sparse coding performs well in image classification. However, robust target recognition requires a lot of comprehensive template images and the sparse learning process is complex. We incorporate sparsity into a template matching concept to construct a local sparse structure matching (LSSM) model for general infrared target recognition. A local structure preserving sparse coding (LSPSc) formulation is proposed to simultaneously preserve the local sparse and structural information of objects. By adding a spatial local structure constraint into the classical sparse coding algorithm, LSPSc can improve the stability of sparse representation for targets and inhibit background interference in infrared images. Furthermore, a kernel LSPSc (K-LSPSc) formulation is proposed, which extends LSPSc to the kernel space to weaken the influence of the linear structure constraint in nonlinear natural data. Because of the anti-interference and fault-tolerant capabilities, both LSPSc- and K-LSPSc-based LSSM can implement target identification based on a simple template set, which just needs several images containing enough local sparse structures to learn a sufficient sparse structure dictionary of a target class. Specifically, this LSSM approach has stable performance in the target detection with scene, shape and occlusions variations. High performance is demonstrated on several datasets, indicating robust infrared target recognition in diverse environments and imaging conditions. PMID:28323824

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

PubMed

Schubert, Peter; Devine, Dana V

2010-01-03

Proteomics has brought new perspectives to the fields of hematology and transfusion medicine in the last decade. The steady improvement of proteomic technology is propelling novel discoveries of molecular mechanisms by studying protein expression, post-translational modifications and protein interactions. This review article focuses on the application of proteomics to the identification of molecular mechanisms leading to the deterioration of blood platelets during storage - a critical aspect in the provision of platelet transfusion products. Several proteomic approaches have been employed to analyse changes in the platelet protein profile during storage and the obtained data now need to be translated into platelet biochemistry in order to connect the results to platelet function. Targeted biochemical applications then allow the identification of points for intervention in signal transduction pathways. Once validated and placed in a transfusion context, these data will provide further understanding of the underlying molecular mechanisms leading to platelet storage lesion. Future aspects of proteomics in blood banking will aim to make use of protein markers identified for platelet storage lesion development to monitor proteome changes when alterations such as the use of additive solutions or pathogen reduction strategies are put in place in order to improve platelet quality for patients. (c) 2009 Elsevier B.V. All rights reserved.

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...

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.

A targeted mass spectrometry-based approach for the identification and characterization of proteins containing α-aminoadipic and γ-glutamic semialdehyde residues

PubMed Central

Chavez, Juan D.; Bisson, William H.

2011-01-01

The site-specific identification of α-aminoadipic semialdehyde (AAS) and γ-glutamic semialdehyde (GGS) residues in proteins is reported. Semialdehydic protein modifications result from the metal-catalyzed oxidation of Lys or Arg and Pro residues, respectively. Most of the analytical methods for the analysis of protein carbonylation measure change to the global level of carbonylation and fail to provide details regarding protein identity, site, and chemical nature of the carbonylation. In this work, we used a targeted approach, which combines chemical labeling, enrichment, and tandem mass spectrometric analysis, for the site-specific identification of AAS and GGS sites in proteins. The approach is applied to in vitro oxidized glyceraldehyde-3-phosphate dehydrogenase (GAPDH) and an untreated biological sample, namely cardiac mitochondrial proteins. The analysis of GAPDH resulted in the site-specific identification of two AAA and four GGS residues. Computational evaluation of the identified AAS and GGS sites in GAPDH indicated that these sites are located in flexible regions, show high solvent accessibility values, and are in proximity with possible metal ion binding sites. The targeted proteomic analysis of semialdehydic modifications in cardiac mitochondria yielded nine AAS modification sites which were unambiguously assigned to distinct lysine residues in the following proteins: ATP/ATP translocase isoforms 1 and 2, ubiquinol cytochrome-c reductase core protein 2, and ATP synthase α-subunit. PMID:20957471

9 CFR 130.15 - User fees for veterinary diagnostic isolation and identification tests performed at NVSL...

Code of Federal Regulations, 2011 CFR

2011-01-01

... 9 Animals and Animal Products 1 2011-01-01 2011-01-01 false User fees for veterinary diagnostic isolation and identification tests performed at NVSL (excluding FADDL) or other authorized site. 130.15... AGRICULTURE USER FEES USER FEES § 130.15 User fees for veterinary diagnostic isolation and identification...

9 CFR 130.15 - User fees for veterinary diagnostic isolation and identification tests performed at NVSL...

Code of Federal Regulations, 2010 CFR

2010-01-01

... 9 Animals and Animal Products 1 2010-01-01 2010-01-01 false User fees for veterinary diagnostic isolation and identification tests performed at NVSL (excluding FADDL) or other authorized site. 130.15... AGRICULTURE USER FEES USER FEES § 130.15 User fees for veterinary diagnostic isolation and identification...

Empirical performance of the self-controlled case series design: lessons for developing a risk identification and analysis system.

PubMed

Suchard, Marc A; Zorych, Ivan; Simpson, Shawn E; Schuemie, Martijn J; Ryan, Patrick B; Madigan, David

2013-10-01

The self-controlled case series (SCCS) offers potential as an statistical method for risk identification involving medical products from large-scale observational healthcare data. However, analytic design choices remain in encoding the longitudinal health records into the SCCS framework and its risk identification performance across real-world databases is unknown. To evaluate the performance of SCCS and its design choices as a tool for risk identification in observational healthcare data. We examined the risk identification performance of SCCS across five design choices using 399 drug-health outcome pairs in five real observational databases (four administrative claims and one electronic health records). In these databases, the pairs involve 165 positive controls and 234 negative controls. We also consider several synthetic databases with known relative risks between drug-outcome pairs. We evaluate risk identification performance through estimating the area under the receiver-operator characteristics curve (AUC) and bias and coverage probability in the synthetic examples. The SCCS achieves strong predictive performance. Twelve of the twenty health outcome-database scenarios return AUCs >0.75 across all drugs. Including all adverse events instead of just the first per patient and applying a multivariate adjustment for concomitant drug use are the most important design choices. However, the SCCS as applied here returns relative risk point-estimates biased towards the null value of 1 with low coverage probability. The SCCS recently extended to apply a multivariate adjustment for concomitant drug use offers promise as a statistical tool for risk identification in large-scale observational healthcare databases. Poor estimator calibration dampens enthusiasm, but on-going work should correct this short-coming.

The effect on cadaver blood DNA identification by the use of targeted and whole body post-mortem computed tomography angiography.

PubMed

Rutty, Guy N; Barber, Jade; Amoroso, Jasmin; Morgan, Bruno; Graham, Eleanor A M

2013-12-01

Post-mortem computed tomography angiography (PMCTA) involves the injection of contrast agents. This could have both a dilution effect on biological fluid samples and could affect subsequent post-contrast analytical laboratory processes. We undertook a small sample study of 10 targeted and 10 whole body PMCTA cases to consider whether or not these two methods of PMCTA could affect post-PMCTA cadaver blood based DNA identification. We used standard methodology to examine DNA from blood samples obtained before and after the PMCTA procedure. We illustrate that neither of these PMCTA methods had an effect on the alleles called following short tandem repeat based DNA profiling, and therefore the ability to undertake post-PMCTA blood based DNA identification.

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

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

PubMed Central

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

2014-01-01

MicroRNAs (miRNAs) are a class of endogenous, approximately 21nt in length, non-coding RNA, which mediate the expression of target genes primarily at post-transcriptional levels. miRNAs play critical roles in almost all plant cellular and metabolic processes. Although numerous miRNAs have been identified in the plant kingdom, the miRNAs in blueberry, which is an economically important small fruit crop, still remain totally unknown. In this study, we reported a computational identification of miRNAs and their targets in blueberry. By conducting an EST-based comparative genomics approach, 9 potential vco-miRNAs were discovered from 22,402 blueberry ESTs according to a series of filtering criteria, designated as vco-miR156–5p, vco-miR156–3p, vco-miR1436, vco-miR1522, vco-miR4495, vco-miR5120, vco-miR5658, vco-miR5783, and vco-miR5986. Based on sequence complementarity between miRNA and its target transcript, 34 target ESTs from blueberry and 70 targets from other species were identified for the vco-miRNAs. The targets were found to be involved in transcription, RNA splicing and binding, DNA duplication, signal transduction, transport and trafficking, stress response, as well as synthesis and metabolic process. These findings will greatly contribute to future research in regard to functions and regulatory mechanisms of blueberry miRNAs. PMID:25763692

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

PubMed

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

2014-01-01

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

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.

Autonomous target tracking of UAVs based on low-power neural network hardware

NASA Astrophysics Data System (ADS)

Yang, Wei; Jin, Zhanpeng; Thiem, Clare; Wysocki, Bryant; Shen, Dan; Chen, Genshe

2014-05-01

Detecting and identifying targets in unmanned aerial vehicle (UAV) images and videos have been challenging problems due to various types of image distortion. Moreover, the significantly high processing overhead of existing image/video processing techniques and the limited computing resources available on UAVs force most of the processing tasks to be performed by the ground control station (GCS) in an off-line manner. In order to achieve fast and autonomous target identification on UAVs, it is thus imperative to investigate novel processing paradigms that can fulfill the real-time processing requirements, while fitting the size, weight, and power (SWaP) constrained environment. In this paper, we present a new autonomous target identification approach on UAVs, leveraging the emerging neuromorphic hardware which is capable of massively parallel pattern recognition processing and demands only a limited level of power consumption. A proof-of-concept prototype was developed based on a micro-UAV platform (Parrot AR Drone) and the CogniMemTMneural network chip, for processing the video data acquired from a UAV camera on the y. The aim of this study was to demonstrate the feasibility and potential of incorporating emerging neuromorphic hardware into next-generation UAVs and their superior performance and power advantages towards the real-time, autonomous target tracking.

Attitude identification for SCOLE using two infrared cameras

NASA Technical Reports Server (NTRS)

Shenhar, Joram

1991-01-01

An algorithm is presented that incorporates real time data from two infrared cameras and computes the attitude parameters of the Spacecraft COntrol Lab Experiment (SCOLE), a lab apparatus representing an offset feed antenna attached to the Space Shuttle by a flexible mast. The algorithm uses camera position data of three miniature light emitting diodes (LEDs), mounted on the SCOLE platform, permitting arbitrary camera placement and an on-line attitude extraction. The continuous nature of the algorithm allows identification of the placement of the two cameras with respect to some initial position of the three reference LEDs, followed by on-line six degrees of freedom attitude tracking, regardless of the attitude time history. A description is provided of the algorithm in the camera identification mode as well as the mode of target tracking. Experimental data from a reduced size SCOLE-like lab model, reflecting the performance of the camera identification and the tracking processes, are presented. Computer code for camera placement identification and SCOLE attitude tracking is listed.

EOID Model Validation and Performance Prediction

DTIC Science & Technology

2002-09-30

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 two most prominent technologies in this area

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.

Effects of target and distractor saturations on the cognitive performance of an integrated display interface

NASA Astrophysics Data System (ADS)

Xue, Chengqi; Li, Jing; Wang, Haiyan; Niu, Yafeng

2015-01-01

Color coding is often used to enhance decision quality in complex man-machine interfaces of integrated display systems. However, people are easily distracted by irrelevant colors and by the numerous data points and complex structures in the interface. Although an increasing number of studies are seriously focusing on the problem of achieving efficient color coding, few are able to determine the effects of target and distractor saturations on cognitive performance. To study the performances of target colors among distractors, a systematic experiment is conducted to assess the influence of high and low saturated targets on cognitive performance, and the affecting extent of different saturated distractors of homogeneous colors on targets. According to the analysis of the reaction time through the non-parametric statistical method, a calculation method of the cognitive performance of each color is proposed. Based on the calculation of the color differences and the accumulation of the reaction times, it is shown that with the different saturated distractors of homogeneous colors, the high saturated yellow targets perform better than the low saturated ones, and the green and blue targets have moderate performances. When searching for a singleton target placed on a black background, the color difference between the target and the distractor should be more than 20Δ E*ab units in the yellow saturation coding, whereas the color difference should be more than 40Δ E*ab units in the blue and green saturation coding. In addition, as regards saturation coding, the influence of the color difference between the target and the background on cognitive performance is greater than that of the color difference between the target and the distractor. Seemingly, the hue attribute determines whether the saturation difference between the target and the distractor affects the cognitive performance. Based on the experimental results, the simulation design of the instrument dials in a flight

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.

Performance of tensor decomposition-based modal identification under nonstationary vibration

NASA Astrophysics Data System (ADS)

Friesen, P.; Sadhu, A.

2017-03-01

Health monitoring of civil engineering structures is of paramount importance when they are subjected to natural hazards or extreme climatic events like earthquake, strong wind gusts or man-made excitations. Most of the traditional modal identification methods are reliant on stationarity assumption of the vibration response and posed difficulty while analyzing nonstationary vibration (e.g. earthquake or human-induced vibration). Recently tensor decomposition based methods are emerged as powerful and yet generic blind (i.e. without requiring a knowledge of input characteristics) signal decomposition tool for structural modal identification. In this paper, a tensor decomposition based system identification method is further explored to estimate modal parameters using nonstationary vibration generated due to either earthquake or pedestrian induced excitation in a structure. The effects of lag parameters and sensor densities on tensor decomposition are studied with respect to the extent of nonstationarity of the responses characterized by the stationary duration and peak ground acceleration of the earthquake. A suite of more than 1400 earthquakes is used to investigate the performance of the proposed method under a wide variety of ground motions utilizing both complete and partial measurements of a high-rise building model. Apart from the earthquake, human-induced nonstationary vibration of a real-life pedestrian bridge is also used to verify the accuracy of the proposed method.

Treponema pallidum Putative Novel Drug Target Identification and Validation: Rethinking Syphilis Therapeutics with Plant-Derived Terpenoids

PubMed Central

Tiwari, Sameeksha; Singh, Priyanka; Singh, Swati; Awasthi, Manika; Pandey, Veda P.

2015-01-01

Abstract Syphilis, a slow progressive and the third most common sexually transmitted disease found worldwide, is caused by a spirochete gram negative bacteria Treponema pallidum. Emergence of antibiotic resistant T. pallidum has led to a search for novel drugs and their targets. Subtractive genomics analyses of pathogen T. pallidum and host Homo sapiens resulted in identification of 126 proteins essential for survival and viability of the pathogen. Metabolic pathway analyses of these essential proteins led to discovery of nineteen proteins distributed among six metabolic pathways unique to T. pallidum. One hundred plant-derived terpenoids, as potential therapeutic molecules against T. pallidum, were screened for their drug likeness and ADMET (absorption, distribution, metabolism, and toxicity) properties. Subsequently the resulting nine terpenoids were docked with five unique T. pallidum targets through molecular modeling approaches. Out of five targets analyzed, D-alanine:D-alanine ligase was found to be the most promising target, while terpenoid salvicine was the most potent inhibitor. A comparison of the inhibitory potential of the best docked readily available natural compound, namely pomiferin (flavonoid) with that of the best docked terpenoid salvicine, revealed that salvicine was a more potent inhibitor than that of pomiferin. To the best of our knowledge, this is the first report of a terpenoid as a potential therapeutic molecule against T. pallidum with D-alanine:D-alanine ligase as a novel target. Further studies are warranted to evaluate and explore the potential clinical ramifications of these findings in relation to syphilis that has public health importance worldwide. PMID:25683888

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.

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.

Military target task performance after wavefront-guided (WFG) and wavefront-optimized (WFO) photorefractive keratectomy (PRK)

NASA Astrophysics Data System (ADS)

Maurer, Tana; Deaver, Dawne; Howell, Christopher; Moyer, Steve; Nguyen, Oanh; Mueller, Greg; Ryan, Denise; Sia, Rose K.; Stutzman, Richard; Pasternak, Joseph; Bower, Kraig

2014-06-01

Major decisions regarding life and death are routinely made on the modern battlefield, where visual function of the individual soldier can be of critical importance in the decision-making process. Glasses in the combat environment have considerable disadvantages: degradation of short term visual performance can occur as dust and sweat accumulate on lenses during a mission or patrol; long term visual performance can diminish as lenses become increasingly scratched and pitted; during periods of intense physical trauma, glasses can be knocked off the soldier's face and lost or broken. Although refractive surgery offers certain benefits on the battlefield when compared to wearing glasses, it is not without potential disadvantages. As a byproduct of refractive surgery, elevated optical aberrations can be induced, causing decreases in contrast sensitivity and increases in the symptoms of glare, halos, and starbursts. Typically, these symptoms occur under low light level conditions, the same conditions under which most military operations are initiated. With the advent of wavefront aberrometry, we are now seeing correction not only of myopia and astigmatism but of other, smaller optical aberrations that can cause the above symptoms. In collaboration with the Warfighter Refractive Eye Surgery Program and Research Center (WRESP-RC) at Fort Belvoir and Walter Reed National Military Medical Center (WRNMMC), the overall objective of this study is to determine the impact of wavefront guided (WFG) versus wavefront-optimized (WFO) photorefractive keratectomy (PRK) on military task visual performance. Psychophysical perception testing was conducted before and after surgery to measure each participant's performance regarding target detection and identification using thermal imagery. The results are presented here.

Two-dimensional hidden semantic information model for target saliency detection and eyetracking identification

NASA Astrophysics Data System (ADS)

Wan, Weibing; Yuan, Lingfeng; Zhao, Qunfei; Fang, Tao

2018-01-01

Saliency detection has been applied to the target acquisition case. This paper proposes a two-dimensional hidden Markov model (2D-HMM) that exploits the hidden semantic information of an image to detect its salient regions. A spatial pyramid histogram of oriented gradient descriptors is used to extract features. After encoding the image by a learned dictionary, the 2D-Viterbi algorithm is applied to infer the saliency map. This model can predict fixation of the targets and further creates robust and effective depictions of the targets' change in posture and viewpoint. To validate the model with a human visual search mechanism, two eyetrack experiments are employed to train our model directly from eye movement data. The results show that our model achieves better performance than visual attention. Moreover, it indicates the plausibility of utilizing visual track data to identify targets.

Fostering group identification and creativity in diverse groups: the role of individuation and self-verification.

PubMed

Swann, William B; Kwan, Virginia S Y; Polzer, Jeffrey T; Milton, Laurie P

2003-11-01

A longitudinal study examined the interplay of identity negotiation processes and diversity in small groups of master's of business administration (MBA) students. When perceivers formed relatively positive impressions of other group members, higher diversity predicted more individuation of targets. When perceivers formed relatively neutral impressions of other group members, however, higher diversity predicted less individuation of targets. Individuation at the outset of the semester predicted self-verification effects several weeks later, and self-verification, in turn, predicted group identification and creative task performance. The authors conclude that contrary to self-categorization theory, fostering individuation and self-verification in diverse groups may maximize group identification and productivity.

Messenger RNA biomarker signatures for forensic body fluid identification revealed by targeted RNA sequencing.

PubMed

Hanson, E; Ingold, S; Haas, C; Ballantyne, J

2018-05-01

The recovery of a DNA profile from the perpetrator or victim in criminal investigations can provide valuable 'source level' information for investigators. However, a DNA profile does not reveal the circumstances by which biological material was transferred. Some contextual information can be obtained by a determination of the tissue or fluid source of origin of the biological material as it is potentially indicative of some behavioral activity on behalf of the individual that resulted in its transfer from the body. Here, we sought to improve upon established RNA based methods for body fluid identification by developing a targeted multiplexed next generation mRNA sequencing assay comprising a panel of approximately equal sized gene amplicons. The multiplexed biomarker panel includes several highly specific gene targets with the necessary specificity to definitively identify most forensically relevant biological fluids and tissues (blood, semen, saliva, vaginal secretions, menstrual blood and skin). In developing the biomarker panel we evaluated 66 gene targets, with a progressive iteration of testing target combinations that exhibited optimal sensitivity and specificity using a training set of forensically relevant body fluid samples. The current assay comprises 33 targets: 6 blood, 6 semen, 6 saliva, 4 vaginal secretions, 5 menstrual blood and 6 skin markers. We demonstrate the sensitivity and specificity of the assay and the ability to identify body fluids in single source and admixed stains. A 16 sample blind test was carried out by one lab with samples provided by the other participating lab. The blinded lab correctly identified the body fluids present in 15 of the samples with the major component identified in the 16th. Various classification methods are being investigated to permit inference of the body fluid/tissue in dried physiological stains. These include the percentage of reads in a sample that are due to each of the 6 tissues/body fluids tested and

Cosmic Origins Spectrograph: On-Orbit Performance of Target Acquisitions

NASA Astrophysics Data System (ADS)

Penton, Steven V.

2010-07-01

COS is a slit-less spectrograph with a very small aperture (R=1.2500). To achieve the desired wavelength accuracies, HST+COS must center the target to within 0.100 of the center of the aperture for the FUV channel, and 0.0400 for NUV. During SMOV and early Cycle 17 we fine-tuned the COS target acquisition (TA) procedures to exceed this accuracy for all three COS TA modes; NUV imaging, NUV spectroscopic, and FUV spectroscopic. In Cycle 17, we also adjusted the COSto- FGS offsets in the SIAF file. This allows us to recommend skipping the time consuming ACQ/SEARCH in cases where the target coordinates are well known. Here we will compare the on-orbit performance of all COS TA modes in terms of centering accuracy, efficiency, and required signal-to-noise (S/N).

Infrared detection, recognition and identification of handheld objects

NASA Astrophysics Data System (ADS)

Adomeit, Uwe

2012-10-01

A main criterion for comparison and selection of thermal imagers for military applications is their nominal range performance. This nominal range performance is calculated for a defined task and standardized target and environmental conditions. The only standardization available to date is STANAG 4347. The target defined there is based on a main battle tank in front view. Because of modified military requirements, this target is no longer up-to-date. Today, different topics of interest are of interest, especially differentiation between friend and foe and identification of humans. There is no direct way to differentiate between friend and foe in asymmetric scenarios, but one clue can be that someone is carrying a weapon. This clue can be transformed in the observer tasks detection: a person is carrying or is not carrying an object, recognition: the object is a long / medium / short range weapon or civil equipment and identification: the object can be named (e. g. AK-47, M-4, G36, RPG7, Axe, Shovel etc.). These tasks can be assessed experimentally and from the results of such an assessment, a standard target for handheld objects may be derived. For a first assessment, a human carrying 13 different handheld objects in front of his chest was recorded at four different ranges with an IR-dual-band camera. From the recorded data, a perception experiment was prepared. It was conducted with 17 observers in a 13-alternative forced choice, unlimited observation time arrangement. The results of the test together with Minimum Temperature Difference Perceived measurements of the camera and temperature difference and critical dimension derived from the recorded imagery allowed defining a first standard target according to the above tasks. This standard target consist of 2.5 / 3.5 / 5 DRI line pairs on target, 0.24 m critical size and 1 K temperature difference. The values are preliminary and have to be refined in the future. Necessary are different aspect angles, different

Identification of Aspergillus fumigatus and Related Species by Nested PCR Targeting Ribosomal DNA Internal Transcribed Spacer Regions

PubMed Central

Zhao, Jun; Kong, Fanrong; Li, Ruoyu; Wang, Xiaohong; Wan, Zhe; Wang, Duanli

2001-01-01

Aspergillus fumigatus is the most common species that causes invasive aspergillosis. In order to identify A. fumigatus, partial ribosomal DNA (rDNA) from two to six strains of five different Aspergillus species was sequenced. By comparing sequence data from GenBank, we designed specific primer pairs targeting rDNA internal transcribed spacer (ITS) regions of A. fumigatus. A nested PCR method for identification of other A. fumigatus-related species was established by using the primers. To evaluate the specificities and sensitivities of those primers, 24 isolates of A. fumigatus and variants, 8 isolates of Aspergillus nidulans, 7 isolates of Aspergillus flavus and variants, 8 isolates of Aspergillus terreus, 9 isolates of Aspergillus niger, 1 isolate each of Aspergillus parasiticus, Aspergillus penicilloides, Aspergillus versicolor, Aspergillus wangduanlii, Aspergillus qizutongii, Aspergillus beijingensis, and Exophiala dermatitidis, 4 isolates of Candida, 4 isolates of bacteria, and human DNA were used. The nested PCR method specifically identified the A. fumigatus isolates and closely related species and showed a high degree of sensitivity. Additionally, four A. fumigatus strains that were recently isolated from our clinic were correctly identified by this method. Our results demonstrate that these primers are useful for the identification of A. fumigatus and closely related species in culture and suggest further studies for the identification of Aspergillus fumigatus species in clinical specimens. PMID:11376067

Targeting Anti-Cancer Active Compounds: Affinity-Based Chromatographic Assays

PubMed Central

de Moraes, Marcela Cristina; Cardoso, Carmen Lucia; Seidl, Claudia; Moaddel, Ruin; Cass, Quezia Bezerra

2016-01-01

Affinity-based chromatography assays encompass the use of solid supports containing immobilized biological targets to monitor binding events in the isolation , identification and/or characterization of bioactive compounds. This powerful bioanalytical technique allows the screening of potential binders through fast analyses that can be directly performed using isolated substances or complex matrices. An overview of the recent researches in frontal and zonal affinity-based chromatography screening assays, which has been used as a tool in the identification and characterization of new anti-cancer agents, is discussed. In addition, a critical evaluation of the recently emerged ligands fishing assays in complex mixtures is also discussed. PMID:27306095

Evaluating the performance of distributed approaches for modal identification

NASA Astrophysics Data System (ADS)

Krishnan, Sriram S.; Sun, Zhuoxiong; Irfanoglu, Ayhan; Dyke, Shirley J.; Yan, Guirong

2011-04-01

In this paper two modal identification approaches appropriate for use in a distributed computing environment are applied to a full-scale, complex structure. The natural excitation technique (NExT) is used in conjunction with a condensed eigensystem realization algorithm (ERA), and the frequency domain decomposition with peak-picking (FDD-PP) are both applied to sensor data acquired from a 57.5-ft, 10 bay highway sign truss structure. Monte-Carlo simulations are performed on a numerical example to investigate the statistical properties and sensitivity to noise of the two distributed algorithms. Experimental results are provided and discussed.

Targeting specific facial variation for different identification tasks.

PubMed

Aeria, Gillian; Claes, Peter; Vandermeulen, Dirk; Clement, John Gerald

2010-09-10

A conceptual framework that allows faces to be studied and compared objectively with biological validity is presented. The framework is a logical extension of modern morphometrics and statistical shape analysis techniques. Three dimensional (3D) facial scans were collected from 255 healthy young adults. One scan depicted a smiling facial expression and another scan depicted a neutral expression. These facial scans were modelled in a Principal Component Analysis (PCA) space where Euclidean (ED) and Mahalanobis (MD) distances were used to form similarity measures. Within this PCA space, property pathways were calculated that expressed the direction of change in facial expression. Decomposition of distances into property-independent (D1) and dependent components (D2) along these pathways enabled the comparison of two faces in terms of the extent of a smiling expression. The performance of all distances was tested and compared in dual types of experiments: Classification tasks and a Recognition task. In the Classification tasks, individual facial scans were assigned to one or more population groups of smiling or neutral scans. The property-dependent (D2) component of both Euclidean and Mahalanobis distances performed best in the Classification task, by correctly assigning 99.8% of scans to the right population group. The recognition task tested if a scan of an individual depicting a smiling/neutral expression could be positively identified when shown a scan of the same person depicting a neutral/smiling expression. ED1 and MD1 performed best, and correctly identified 97.8% and 94.8% of individual scans respectively as belonging to the same person despite differences in facial expression. It was concluded that decomposed components are superior to straightforward distances in achieving positive identifications and presents a novel method for quantifying facial similarity. Additionally, although the undecomposed Mahalanobis distance often used in practice outperformed

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.

Performance and strategy comparisons of human listeners and logistic regression in discriminating underwater targets.

PubMed

Yang, Lixue; Chen, Kean

2015-11-01

To improve the design of underwater target recognition systems based on auditory perception, this study compared human listeners with automatic classifiers. Performances measures and strategies in three discrimination experiments, including discriminations between man-made and natural targets, between ships and submarines, and among three types of ships, were used. In the experiments, the subjects were asked to assign a score to each sound based on how confident they were about the category to which it belonged, and logistic regression, which represents linear discriminative models, also completed three similar tasks by utilizing many auditory features. The results indicated that the performances of logistic regression improved as the ratio between inter- and intra-class differences became larger, whereas the performances of the human subjects were limited by their unfamiliarity with the targets. Logistic regression performed better than the human subjects in all tasks but the discrimination between man-made and natural targets, and the strategies employed by excellent human subjects were similar to that of logistic regression. Logistic regression and several human subjects demonstrated similar performances when discriminating man-made and natural targets, but in this case, their strategies were not similar. An appropriate fusion of their strategies led to further improvement in recognition accuracy.

Target mimics: an embedded layer of microRNA-involved gene regulatory networks in plants.

PubMed

Meng, Yijun; Shao, Chaogang; Wang, Huizhong; Jin, Yongfeng

2012-05-21

MicroRNAs (miRNAs) play an essential role in gene regulation in plants. At the same time, the expression of miRNA genes is also tightly controlled. Recently, a novel mechanism called "target mimicry" was discovered, providing another layer for modulating miRNA activities. However, except for the artificial target mimics manipulated for functional studies on certain miRNA genes, only one example, IPS1 (Induced by Phosphate Starvation 1)-miR399 was experimentally confirmed in planta. To date, few analyses for comprehensive identification of natural target mimics have been performed in plants. Thus, limited evidences are available to provide detailed information for interrogating the questionable issue whether target mimicry was widespread in planta, and implicated in certain biological processes. In this study, genome-wide computational prediction of endogenous miRNA mimics was performed in Arabidopsis and rice, and dozens of target mimics were identified. In contrast to a recent report, the densities of target mimic sites were found to be much higher within the untranslated regions (UTRs) when compared to those within the coding sequences (CDSs) in both plants. Some novel sequence characteristics were observed for the miRNAs that were potentially regulated by the target mimics. GO (Gene Ontology) term enrichment analysis revealed some functional insights into the predicted mimics. After degradome sequencing data-based identification of miRNA targets, the regulatory networks constituted by target mimics, miRNAs and their downstream targets were constructed, and some intriguing subnetworks were further exploited. These results together suggest that target mimicry may be widely implicated in regulating miRNA activities in planta, and we hope this study could expand the current understanding of miRNA-involved regulatory networks.

Development of high-performance alkali-hybrid polarized 3He targets for electron scattering

NASA Astrophysics Data System (ADS)

Singh, Jaideep T.; Dolph, P. A. M.; Tobias, W. A.; Averett, T. D.; Kelleher, A.; Mooney, K. E.; Nelyubin, V. V.; Wang, Yunxiao; Zheng, Yuan; Cates, G. D.

2015-05-01

Background: Polarized 3He targets have been used as effective polarized neutron targets for electron scattering experiments for over twenty years. Over the last ten years, the effective luminosity of polarized 3He targets based on spin-exchange optical pumping has increased by over an order of magnitude. This has come about because of improvements in commercially-available lasers and an improved understanding of the physics behind the polarization process. Purpose: We present the development of high-performance polarized 3He targets for use in electron scattering experiments. Improvements in the performance of polarized 3He targets, target properties, and operating parameters are documented. Methods: We utilize the technique of alkali-hybrid spin-exchange optical pumping to polarize the 3He targets. Spectrally narrowed diode lasers used for the optical pumping greatly improved the performance. A simulation of the alkali-hybrid spin-exchange optical pumping process was developed to provide guidance in the design of the targets. Data was collected during the characterization of 24 separate glass target cells, each of which was constructed while preparing for one of four experiments at Jefferson Laboratory in Newport News, Virginia. Results: From the data obtained we made determinations of the so-called X -factors that quantify a temperature-dependent and as-yet poorly understood spin-relaxation mechanism that limits the maximum achievable 3He polarization to well under 100%. The presence of the X -factor spin-relaxation mechanism was clearly evident in our data. Good agreement between the simulation and the actual target performance was obtained by including details such as off-resonant optical pumping. Included in our results is a measurement of the K -3He spin-exchange rate coefficient kseK=(7.46 ±0.62 ) ×10-20cm3/s over the temperature range 503 K to 563 K. Conclusions: In order to achieve high performance under the operating conditions described in this paper

Molecular basis for the action of a dietary flavonoid revealed by the comprehensive identification of apigenin human targets

PubMed Central

Arango, Daniel; Morohashi, Kengo; Yilmaz, Alper; Kuramochi, Kouji; Parihar, Arti; Brahimaj, Bledi; Grotewold, Erich; Doseff, Andrea I.

2013-01-01

Flavonoids constitute the largest class of dietary phytochemicals, adding essential health value to our diet, and are emerging as key nutraceuticals. Cellular targets for dietary phytochemicals remain largely unknown, posing significant challenges for the regulation of dietary supplements and the understanding of how nutraceuticals provide health value. Here, we describe the identification of human cellular targets of apigenin, a flavonoid abundantly present in fruits and vegetables, using an innovative high-throughput approach that combines phage display with second generation sequencing. The 160 identified high-confidence candidate apigenin targets are significantly enriched in three main functional categories: GTPase activation, membrane transport, and mRNA metabolism/alternative splicing. This last category includes the heterogeneous nuclear ribonucleoprotein A2 (hnRNPA2), a factor involved in splicing regulation, mRNA stability, and mRNA transport. Apigenin binds to the C-terminal glycine-rich domain of hnRNPA2, preventing hnRNPA2 from forming homodimers, and therefore, it perturbs the alternative splicing of several human hnRNPA2 targets. Our results provide a framework to understand how dietary phytochemicals exert their actions by binding to many functionally diverse cellular targets. In turn, some of them may modulate the activity of a large number of downstream genes, which is exemplified here by the effects of apigenin on the alternative splicing activity of hnRNPA2. Hence, in contrast to small-molecule pharmaceuticals designed for defined target specificity, dietary phytochemicals affect a large number of cellular targets with varied affinities that, combined, result in their recognized health benefits. PMID:23697369

Identification of Protein Targets of 4-Hydroxynonenal Using Click Chemistry for Ex Vivo Biotinylation of Azido and Alkynyl Derivatives

PubMed Central

Vila, Andrew; Tallman, Keri A.; Jacobs, Aaron T.; Liebler, Daniel C.; Porter, Ned A.; Marnett, Lawrence J.

2009-01-01

Polyunsaturated fatty acids (PUFA) are primary targets of free radical damage during oxidative stress. Diffusible electrophilic α, β-unsaturated aldehydes, such as 4-hydroxynonenal (HNE), have been shown to modify proteins that mediate cell signaling (e.g. IKK and Keap1) and alter gene expression pathways responsible for inducing antioxidant genes, heat shock proteins, and the DNA damage response. To fully understand cellular responses to HNE, it is important to determine its protein targets in an unbiased fashion. This requires a strategy for detecting and isolating HNE-modified proteins regardless of the nature of the chemical linkage between HNE and its targets. Azido or alkynyl derivatives of HNE were synthesized and demonstrated to be equivalent to HNE in their ability to induce heme oxygenase induction and induce apoptosis in colon cancer (RKO) cells. Cells exposed to the tagged HNE derivatives were lysed and exposed to reagents to effect Staudinger ligation or copper-catalyzed Huisgen 1,3 dipolar cycloaddition reaction (click chemistry) to conjugate HNE-adducted proteins with biotin for subsequent affinity purification. Both strategies yielded efficient biotinylation of tagged HNE-protein conjugates but click chemistry was found to be superior for recovery of biotinylated proteins from streptavidin-coated beads. Biotinylated proteins were detected in lysates from RKO cell incubations with azido-HNE at concentrations as low as 1 μM. These proteins were affinity purified with streptavidin beads and proteomic analysis was performed by linear ion trap mass spectrometry. Proteomic analysis revealed a dose-dependent increase in labeled proteins with increased sequence coverage at higher concentrations. Several proteins involved in stress signaling (heat shock proteins 70 and 90, and the 78-kDa glucose-regulated protein) were selectively adducted by azido- and alkynyl-HNE. The use of azido and alkynyl derivatives in conjunction with click chemistry appears to be

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…

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

Identification of Sarcosine as a Target Molecule for the Canine Olfactory Detection of Prostate Carcinoma.

PubMed

Pacik, Dalibor; Plevova, Mariana; Urbanova, Lucie; Lackova, Zuzana; Strmiska, Vladislav; Necas, Alois; Heger, Zbynek; Adam, Vojtech

2018-03-21

The hypothesis that dogs can detect malignant tumours through the identification of specific molecules is nearly 30 years old. To date, several reports have described the successful detection of distinct types of cancer. However, is still a lack of data regarding the specific molecules that can be recognized by a dog's olfactory apparatus. Hence, we performed a study with artificially prepared, well-characterized urinary specimens that were enriched with sarcosine, a widely reported urinary biomarker for prostate cancer (PCa). For the purposes of the study, a German shepherd dog was utilized for analyses of 60 positive and 120 negative samples. Our study provides the first evidence that a sniffer dog specially trained for the olfactory detection of PCa can recognize sarcosine in artificial urine with a performance [sensitivity of 90%, specificity of 95%, and precision of 90% for the highest amount of sarcosine (10 µmol/L)] that is comparable to the identification of PCa-diagnosed subjects (sensitivity of 93.5% and specificity of 91.6%). This study casts light on the unrevealed phenomenon of PCa olfactory detection and opens the door for further studies with canine olfactory detection and cancer diagnostics.

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 active sources inside cavities using the equivalent source method-based free-field recovery technique

NASA Astrophysics Data System (ADS)

Bi, Chuan-Xing; Hu, Ding-Yu; Zhang, Yong-Bin; Jing, Wen-Qian

2015-06-01

In previous studies, an equivalent source method (ESM)-based technique for recovering the free sound field in a noisy environment has been successfully applied to exterior problems. In order to evaluate its performance when applied to a more general noisy environment, that technique is used to identify active sources inside cavities where the sound field is composed of the field radiated by active sources and that reflected by walls. A patch approach with two semi-closed surfaces covering the target active sources is presented to perform the measurements, and the field that would be radiated by these target active sources into free space is extracted from the mixed field by using the proposed technique, which will be further used as the input of nearfield acoustic holography for source identification. Simulation and experimental results validate the effectiveness of the proposed technique for source identification in cavities, and show the feasibility of performing the measurements with a double layer planar array.

In situ identification of nocardioform actinomycetes in activated sludge using fluorescent rRNA-targeted oligonucleotide probes.

PubMed

Schuppler, M; Wagner, M; Schön, G; Göbel, U B

1998-01-01

Hitherto, few environmental samples have been investigated by a 'full cycle rRNA analysis'. Here the results of in situ hybridization experiments with specific rRNA-targeted oligonucleotide probes developed on the basis of new sequences derived from a previously described comparative 16S rRNA analysis of nocardioform actinomycetes in activated sludge are reported. Application of the specific probes enabled identification and discrimination of the distinct populations of nocardioform actinomycetes in activated sludge. One of the specific probes (DLP) detected rod-shaped bacteria which were found in 13 of the 16 investigated sludge samples from various wastewater treatment plants, suggesting their importance in the wastewater treatment process. Another probe (GLP2) hybridized with typically branched filaments of nocardioforms mainly found in samples from enhanced biological phosphorus removal plants, suggesting that these bacteria are involved in sludge foaming. The combination of in situ hybridization with fluorescently labelled rRNA-targeted oligonucleotide probes and confocal laser scanning microscopy improved the detection of nocardioform actinomycetes, which often showed only weak signals inside the activated-sludge flocs.

Novel drug target identification for the treatment of dementia using multi-relational association mining.

PubMed

Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

2015-07-08

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia.

Novel drug target identification for the treatment of dementia using multi-relational association mining

PubMed Central

Nguyen, Thanh-Phuong; Priami, Corrado; Caberlotto, Laura

2015-01-01

Dementia is a neurodegenerative condition of the brain in which there is a progressive and permanent loss of cognitive and mental performance. Despite the fact that the number of people with dementia worldwide is steadily increasing and regardless of the advances in the molecular characterization of the disease, current medical treatments for dementia are purely symptomatic and hardly effective. We present a novel multi-relational association mining method that integrates the huge amount of scientific data accumulated in recent years to predict potential novel targets for innovative therapeutic treatment of dementia. Owing to the ability of processing large volumes of heterogeneous data, our method achieves a high performance and predicts numerous drug targets including several serine threonine kinase and a G-protein coupled receptor. The predicted drug targets are mainly functionally related to metabolism, cell surface receptor signaling pathways, immune response, apoptosis, and long-term memory. Among the highly represented kinase family and among the G-protein coupled receptors, DLG4 (PSD-95), and the bradikynin receptor 2 are highlighted also for their proposed role in memory and cognition, as described in previous studies. These novel putative targets hold promises for the development of novel therapeutic approaches for the treatment of dementia. PMID:26154857

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

Visual search performance among persons with schizophrenia as a function of target eccentricity.

PubMed

Elahipanah, Ava; Christensen, Bruce K; Reingold, Eyal M

2010-03-01

The current study investigated one possible mechanism of impaired visual attention among patients with schizophrenia: a reduced visual span. Visual span is the region of the visual field from which one can extract information during a single eye fixation. This study hypothesized that schizophrenia-related visual search impairment is mediated, in part, by a smaller visual span. To test this hypothesis, 23 patients with schizophrenia and 22 healthy controls completed a visual search task where the target was pseudorandomly presented at different distances from the center of the display. Response times were analyzed as a function of search condition (feature vs. conjunctive), display size, and target eccentricity. Consistent with previous reports, patient search times were more adversely affected as the number of search items increased in the conjunctive search condition. It was important however, that patients' conjunctive search times were also impacted to a greater degree by target eccentricity. Moreover, a significant impairment in patients' visual search performance was only evident when targets were more eccentric and their performance was more similar to healthy controls when the target was located closer to the center of the search display. These results support the hypothesis that a narrower visual span may underlie impaired visual search performance among patients with schizophrenia. Copyright 2010 APA, all rights reserved

Tools for in silico target fishing.

PubMed

Cereto-Massagué, Adrià; Ojeda, María José; Valls, Cristina; Mulero, Miquel; Pujadas, Gerard; Garcia-Vallve, Santiago

2015-01-01

Computational target fishing methods are designed to identify the most probable target of a query molecule. This process may allow the prediction of the bioactivity of a compound, the identification of the mode of action of known drugs, the detection of drug polypharmacology, drug repositioning or the prediction of the adverse effects of a compound. The large amount of information regarding the bioactivity of thousands of small molecules now allows the development of these types of methods. In recent years, we have witnessed the emergence of many methods for in silico target fishing. Most of these methods are based on the similarity principle, i.e., that similar molecules might bind to the same targets and have similar bioactivities. However, the difficult validation of target fishing methods hinders comparisons of the performance of each method. In this review, we describe the different methods developed for target prediction, the bioactivity databases most frequently used by these methods, and the publicly available programs and servers that enable non-specialist users to obtain these types of predictions. It is expected that target prediction will have a large impact on drug development and on the functional food industry. Copyright © 2014 Elsevier Inc. All rights reserved.

Identification-While-Scanning of a Multi-Aircraft Formation Based on Sparse Recovery for Narrowband Radar.

PubMed

Jiang, Yuan; Xu, Jia; Peng, Shi-Bao; Mao, Er-Ke; Long, Teng; Peng, Ying-Ning

2016-11-23

It is known that the identification performance of a multi-aircraft formation (MAF) of narrowband radar mainly depends on the time on target (TOT). To realize the identification task in one rotated scan with limited TOT, the paper proposes a novel identification-while-scanning (IWS) method based on sparse recovery to maintain high rotating speed and super-resolution for MAF identification, simultaneously. First, a multiple chirp signal model is established for MAF in a single scan, where different aircraft may have different Doppler centers and Doppler rates. Second, based on the sparsity of MAF in the Doppler parameter space, a novel hierarchical basis pursuit (HBP) method is proposed to obtain satisfactory sparse recovery performance as well as high computational efficiency. Furthermore, the parameter estimation performance of the proposed IWS identification method is analyzed with respect to recovery condition, signal-to-noise ratio and TOT. It is shown that an MAF can be effectively identified via HBP with a TOT of only about one hundred microseconds for IWS applications. Finally, some numerical experiment results are provided to demonstrate the effectiveness of the proposed method based on both simulated and real measured data.

Signal detection theory applied to three visual search tasks--identification, yes/no detection and localization.

PubMed

Cameron, E Leslie; Tai, Joanna C; Eckstein, Miguel P; Carrasco, Marisa

2004-01-01

Adding distracters to a display impairs performance on visual tasks (i.e. the set-size effect). While keeping the display characteristics constant, we investigated this effect in three tasks: 2 target identification, yes-no detection with 2 targets, and 8-alternative localization. A Signal Detection Theory (SDT) model, tailored for each task, accounts for the set-size effects observed in identification and localization tasks, and slightly under-predicts the set-size effect in a detection task. Given that sensitivity varies as a function of spatial frequency (SF), we measured performance in each of these three tasks in neutral and peripheral precue conditions for each of six spatial frequencies (0.5-12 cpd). For all spatial frequencies tested, performance on the three tasks decreased as set size increased in the neutral precue condition, and the peripheral precue reduced the effect. Larger set-size effects were observed at low SFs in the identification and localization tasks. This effect can be described using the SDT model, but was not predicted by it. For each of these tasks we also established the extent to which covert attention modulates performance across a range of set sizes. A peripheral precue substantially diminished the set-size effect and improved performance, even at set size 1. These results provide support for distracter exclusion, and suggest that signal enhancement may also be a mechanism by which covert attention can impose its effect.

Measuring target detection performance in paradigms with high event rates.

PubMed

Bendixen, Alexandra; Andersen, Søren K

2013-05-01

Combining behavioral and neurophysiological measurements inevitably implies mutual constraints, such as when the neurophysiological measurement requires fast-paced stimulus presentation and hence the attribution of a behavioral response to a particular preceding stimulus becomes ambiguous. We develop and test a method for validly assessing behavioral detection performance in spite of this ambiguity. We examine four approaches taken in the literature to treat such situations. We analytically derive a new variant of computing the classical parameters of signal detection theory, hit and false alarm rates, adapted to fast-paced paradigms. Each of the previous approaches shows specific shortcomings (susceptibility towards response window choice, biased estimates of behavioral detection performance). Superior performance of our new approach is demonstrated for both simulated and empirical behavioral data. Further evidence is provided by reliable correspondence between behavioral performance and the N2b component as an electrophysiological indicator of target detection. The appropriateness of our approach is substantiated by both theoretical and empirical arguments. We demonstrate an easy-to-implement solution for measuring target detection performance independent of the rate of event presentation. Thus overcoming the measurement bias of previous approaches, our method will help to clarify the behavioral relevance of different measures of cortical activation. Copyright © 2012 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

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.

A RICH detector for hadron identification at Jlab

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

Mammoliti, Francesco; Cisbani, Evaristo; Cusanno, Francesco

2011-08-01

The “standard” Hall A apparatus at Jefferson Lab (TOF and aerogel threshold Cherenkov detectors) does not provide complete identification for proton, kaon and pion. To this aim, a proximity focusing C6F14/CsI RICH (Ring Image Cherenkov) detector has been designed, built, tested and operated to separate kaons from pions with a pion contamination of a few percent up to 2.4 GeV/c. Two quite different experimental investigations have benefitted of the RICH identification: on one side, the high-resolution hypernuclear spectroscopy series of experiments on carbon, beryllium and oxygen, devoted to the study of the lambda-nucleon potential. On the other side, the measurementsmore » of the single spin asymmetries of pion and kaon on a transversely polarized 3He target are of utmost interest in understanding QCD dynamics in the nucleon. We present the technical features of such a RICH detector and comment on the presently achieved performance in hadron identification.« less

The identification of cellular targets of 17β estradiol using a lytic (T7) cDNA phage display approach.

PubMed

Van Dorst, Bieke; Mehta, Jaytry; Rouah-Martin, Elsa; De Coen, Wim; Blust, Ronny; Robbens, Johan

2011-02-01

To unravel the mechanism of action of chemical compounds, it is crucial to know their cellular targets. A novel in vitro tool that can be used as a fast, simple and cost effective alternative is cDNA phage display. This tool is used in our study to select cellular targets of 17β estradiol (E2). It was possible to select two potential cellular targets of E2 out of the T7 Select™ Human Breast cDNA phage library. The selected cellular targets, autophagy/beclin-1 regulator 1 (beclin 1) and ATP synthase F(0) subunit 6 (ATP6) have so far been unknown as binding proteins of E2. To confirm the E2 binding properties of these selected proteins, surface plasmon resonance (SPR) was used. With SPR the K(d) values were determined to be 0.178±0.031 and 0.401±0.142 nM for the ATP6 phage and beclin 1 phage, respectively. These K(d) values in the low nM range verify that the selected cellular proteins are indeed binding proteins for E2. The selection and identification of these two potential cellular targets of E2, can enhance our current understanding of its mechanism of action. This illustrates the potential of lytic (T7) cDNA phage display in toxicology, to provide important information about cellular targets of chemical compounds. Copyright © 2010 Elsevier Ltd. All rights reserved.

Identification of Five Novel Variants in Chinese Oculocutaneous Albinism by Targeted Next-Generation Sequencing.

PubMed

Qiu, Biyuan; Ma, Tao; Peng, Chunyan; Zheng, Xiaoqin; Yang, Jiyun

2018-04-01

The diagnosis of oculocutaneous albinism (OCA) is established using clinical signs and symptoms. OCA is, however, a highly genetically heterogeneous disease with mutations identified in at least nineteen unique genes, many of which produce overlapping phenotypic traits. Thus, differentiating genetic OCA subtypes for diagnoses and genetic counseling is challenging, based on clinical presentation alone, and would benefit from a comprehensive molecular diagnostic. To develop and validate a more comprehensive, targeted, next-generation-sequencing-based diagnostic for the identification of OCA-causing variants. The genomic DNA samples from 28 OCA probands were analyzed by targeted next-generation sequencing (NGS), and the candidate variants were confirmed through Sanger sequencing. We observed mutations in the TYR, OCA2, and SLC45A2 genes in 25/28 (89%) patients with OCA. We identified 38 pathogenic variants among these three genes, including 5 novel variants: c.1970G>T (p.Gly657Val), c.1669A>C (p.Thr557Pro), c.2339-2A>C, and c.1349C>G (p.Thr450Arg) in OCA2; c.459_470delTTTTGCTGCCGA (p.Ala155_Phe158del) in SLC45A2. Our findings expand the mutational spectrum of OCA in the Chinese population, and the assay we developed should be broadly useful as a molecular diagnostic, and as an aid for genetic counseling for OCA patients.

Charged Particle Identification for Prefragmentation Studies

NASA Astrophysics Data System (ADS)

Hu, Jonathan; MoNA Collaboration

2017-09-01

Projectile fragmentation refers to high energy (>50 MeV/u) heavy ion beams on production targets to generate intermediate mass and target fragments at facilities like the NSCL, FRIB, GSI, GANIL and RIKEN. The resulting secondary beams can then be isolated by fragment separators like the NCSL's A1900 and that secondary beam then used on reaction targets for a variety of experiments. Predictions of beam intensities for experiment planning depend on models and data. The MoNA Collaboration performed an experiment at the NSCL in which a 48Ca primary beam was used with a 9Be target to produce a 32Mg secondary beam with energy 86 MeV/u that was incident on a second target of 9Be. By characterizing the energy distributions of final fragments of neon, sodium, and fluorine in coincidence with neutrons created both by prefragmentation processes and reaction mechanisms, we are able to extract information about prefragmentation dynamics. The identification of charged fragments is a multi-step process crucial to this analysis. This work is supported by the National Science Foundation under Grant No. PHY-1613429.

Making gender matter: the role of gender-based expectancies and gender identification on women's and men's math performance in Sweden.

PubMed

Eriksson, Kimmo; Lindholm, Torun

2007-08-01

It is well established that an emphasis on gender differences may have a negative effect on women's math performance in USA, Germany and the Netherlands. It has further been found that an individual's identification with the stereotyped group may moderate effects of negative stereotypes. The present study investigated how gender-based expectancies affected the math performance of women and men in Sweden, a nation with a smaller gender gap than in other countries, and a strong cultural emphasis on gender equality. Participants, 112 female and 74 male undergraduate math students from Swedish universities, completed a difficult math test in which their gender was either linked to their test performance or not. Men performed better than women when gender was made relevant among participants who did not see their gender as an important aspect of their identity, while participants high in gender identification were unaffected by gender identity relevance. Moreover, the gender relevance manipulation affected men's performance more than women's. The results deviate from findings on US samples, indicating that the role of group identification as a moderator of stereotype-based expectancy effects is complex, and that factors in the cultural context may interact with individual differences in identification to determine the impact of negative stereotypes.

Development and validation of a multiplex real-time PCR method to simultaneously detect 47 targets for the identification of genetically modified organisms.

PubMed

Cottenet, Geoffrey; Blancpain, Carine; Sonnard, Véronique; Chuah, Poh Fong

2013-08-01

Considering the increase of the total cultivated land area dedicated to genetically modified organisms (GMO), the consumers' perception toward GMO and the need to comply with various local GMO legislations, efficient and accurate analytical methods are needed for their detection and identification. Considered as the gold standard for GMO analysis, the real-time polymerase chain reaction (RTi-PCR) technology was optimised to produce a high-throughput GMO screening method. Based on simultaneous 24 multiplex RTi-PCR running on a ready-to-use 384-well plate, this new procedure allows the detection and identification of 47 targets on seven samples in duplicate. To comply with GMO analytical quality requirements, a negative and a positive control were analysed in parallel. In addition, an internal positive control was also included in each reaction well for the detection of potential PCR inhibition. Tested on non-GM materials, on different GM events and on proficiency test samples, the method offered high specificity and sensitivity with an absolute limit of detection between 1 and 16 copies depending on the target. Easy to use, fast and cost efficient, this multiplex approach fits the purpose of GMO testing laboratories.

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

Electro-Optic Identification (EOID) Research Program

DTIC Science & Technology

2002-09-30

The goal of this research is to provide computer-assisted identification of underwater mines in electro - optic imagery. Identification algorithms will...greatly reduce the time and risk to reacquire mine-like-objects for positive classification and identification. The objectives are to collect electro ... optic data under a wide range of operating and environmental conditions and develop precise algorithms that can provide accurate target recognition on this data for all possible conditions.

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).

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

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

Hayakawa, Kazuo; Department of Cell Growth and Differentiation, Center for iPS Cell Research and Application, Kyoto University, Kyoto; Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Nagoya City University, Nagoya

2013-03-22

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

Blind sequential lineup administration reduces both false identifications and confidence in those false identifications.

PubMed

Charman, Steve D; Quiroz, Vanessa

2016-10-01

One of the most recommended procedures proposed by eyewitness experts is the use of double-blind lineups, in which the administrator does not know the identity of the suspect in the lineup. But despite the near universality of this recommendation, there is surprisingly little empirical research to support the claim that nonblind administration inflates false identifications. What little research has been conducted has shown conflicting findings with regard to the conditions under which nonblind administration affects false identifications, as well as its effects on witness confidence. The current study attempts to elucidate this effect. Student-participants (n = 312) were randomly assigned to play the role of either a lineup administrator (who were either told the identity of the suspect in the lineup or not) or a mock crime witness. Following unbiased instructions, administrators presented either a target-present or target-absent sequential lineup to the witness while being surreptitiously videorecorded. Nonblind administration significantly inflated false, but not correct, identifications, and significantly inflated witness confidence in those false identifications. Video recordings indicated that nonblind administrators were significantly more likely than blind administrators to smile (a) while the witness was viewing a photograph of the suspect, and (b) after a suspect identification. Results provide stronger support for the use of blind lineup administration by broadening the conditions under which nonblind administration is shown to inflate false identifications. Possible reconciliations for conflicting findings in the literature are discussed. (PsycINFO Database Record (c) 2016 APA, all rights reserved).

Computer-aided identification of novel protein targets of bisphenol A.

PubMed

Montes-Grajales, Diana; Olivero-Verbel, Jesus

2013-10-09

The xenoestrogen bisphenol A (2,2-bis-(p-hydroxyphenyl)-2-propane, BPA) is a known endocrine-disrupting chemical used in the fabrication of plastics, resins and flame retardants, that can be found throughout the environment and in numerous every day products. Human exposure to this chemical is extensive and generally occurs via oral route because it leaches from the food and beverage containers that contain it. Although most of the effects related to BPA exposure have been linked to the activation of the estrogen receptor (ER), the mechanisms of the interaction of BPA with protein targets different from ER are still unknown. Therefore, the objective of this work was to use a bioinformatics approach to identify possible new targets for BPA. Docking studies were performed between the optimized structure of BPA and 271 proteins related to different biochemical processes, as selected by text-mining. Refinement docking experiments and conformational analyses were carried out using LigandScout 3.0 for the proteins selected through the affinity ranking (lower than -8.0kcal/mol). Several proteins including ERR gamma (-9.9kcal/mol), and dual specificity protein kinases CLK-4 (-9.5kcal/mol), CLK-1 (-9.1kcal/mol) and CLK-2 (-9.0kcal/mol) presented great in silico binding affinities for BPA. The interactions between those proteins and BPA were mostly hydrophobic with the presence of some hydrogen bonds formed by leucine and asparagine residues. Therefore, this study suggests that this endocrine disruptor may have other targets different from the ER. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

The Link between Basing Self-Worth on Academics and Student Performance Depends on Domain Identification and Academic Setting

ERIC Educational Resources Information Center

Lawrence, Jason S.; Charbonneau, Joseph

2009-01-01

Two studies showed that the link between how much students base their self-worth on academics and their math performance depends on whether their identification with math was statistically controlled and whether the task measured ability or not. Study 1 showed that, when math identification was uncontrolled and the task was ability-diagnostic,…

Neutronics performance and activation calculation of dense tungsten granular target for China-ADS

NASA Astrophysics Data System (ADS)

Zhang, Yaling; Li, Jianyang; Zhang, Xunchao; Cai, Hanjie; Yan, Xuesong; Yu, Lin; Fu, Fen; Lin, Ping; Gao, Xiaofei; Zhang, Zhilei; Zhang, Yanshi; Yang, Lei

2017-11-01

Spallation target, which constitutes the physical and functional interface between the high power accelerator and the subcritical core, is one of the most important components in Accelerator Driven Subcritical System (ADS). In this paper, we investigated the neutronics performance, the radiation damage and the activation of dense tungsten granular flow spallation target by using the Monte Carlo programs GMT and FLUKA at the proton energy of 250 MeV with a beam current of 10 mA . First, the leaking neutron yield, leaking neutron energy spectrum and laterally leaking neutron distribution at several time nodes and with different target parameters are explored. After that, the displacement per atom (DPA) and the helium/hydrogen production for tungsten grains and structural materials with stainless steel 316L are estimated. Finally, the radioactivity, residual dose rate and afterheat of granular target are presented. Results indicate that granule diameter below 1 cm and the beam profile diameter have negligible impact on neutronics performance, while the target diameter and volume fraction of grain have notable influence. The maximum DPA for target vessel (beam tube) is about 1.0 (1.6) DPA/year in bare target, and increased to 2.6 (2.8) DPA/year in fission environment. Average DPA for tungsten grains is relatively low. The decline rate of radioactivity and afterheat with cooling time grows with the decrease of the irradiation time.

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification

PubMed Central

Ballester, Pedro J.; Mangold, Martina; Howard, Nigel I.; Robinson, Richard L. Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B. O.

2012-01-01

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated Ki ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification. PMID:22933186

Hierarchical virtual screening for the discovery of new molecular scaffolds in antibacterial hit identification.

PubMed

Ballester, Pedro J; Mangold, Martina; Howard, Nigel I; Robinson, Richard L Marchese; Abell, Chris; Blumberger, Jochen; Mitchell, John B O

2012-12-07

One of the initial steps of modern drug discovery is the identification of small organic molecules able to inhibit a target macromolecule of therapeutic interest. A small proportion of these hits are further developed into lead compounds, which in turn may ultimately lead to a marketed drug. A commonly used screening protocol used for this task is high-throughput screening (HTS). However, the performance of HTS against antibacterial targets has generally been unsatisfactory, with high costs and low rates of hit identification. Here, we present a novel computational methodology that is able to identify a high proportion of structurally diverse inhibitors by searching unusually large molecular databases in a time-, cost- and resource-efficient manner. This virtual screening methodology was tested prospectively on two versions of an antibacterial target (type II dehydroquinase from Mycobacterium tuberculosis and Streptomyces coelicolor), for which HTS has not provided satisfactory results and consequently practically all known inhibitors are derivatives of the same core scaffold. Overall, our protocols identified 100 new inhibitors, with calculated K(i) ranging from 4 to 250 μM (confirmed hit rates are 60% and 62% against each version of the target). Most importantly, over 50 new active molecular scaffolds were discovered that underscore the benefits that a wide application of prospectively validated in silico screening tools is likely to bring to antibacterial hit identification.

[Thalidomide teratogenicity and its direct target identification].

PubMed

Ito, Takumi; Ando, Hideki; Handa, Hiroshi

2015-01-01

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

Identifying MicroRNAs and Transcript Targets in Jatropha Seeds

PubMed Central

Galli, Vanessa; Guzman, Frank; de Oliveira, Luiz F. V.; Loss-Morais, Guilherme; Körbes, Ana P.; Silva, Sérgio D. A.; Margis-Pinheiro, Márcia M. A. N.; Margis, Rogério

2014-01-01

MicroRNAs, or miRNAs, are endogenously encoded small RNAs that play a key role in diverse plant biological processes. Jatropha curcas L. has received significant attention as a potential oilseed crop for the production of renewable oil. Here, a sRNA library of mature seeds and three mRNA libraries from three different seed development stages were generated by deep sequencing to identify and characterize the miRNAs and pre-miRNAs of J. curcas. Computational analysis was used for the identification of 180 conserved miRNAs and 41 precursors (pre-miRNAs) as well as 16 novel pre-miRNAs. The predicted miRNA target genes are involved in a broad range of physiological functions, including cellular structure, nuclear function, translation, transport, hormone synthesis, defense, and lipid metabolism. Some pre-miRNA and miRNA targets vary in abundance between the three stages of seed development. A search for sequences that produce siRNA was performed, and the results indicated that J. curcas siRNAs play a role in nuclear functions, transport, catalytic processes and disease resistance. This study presents the first large scale identification of J. curcas miRNAs and their targets in mature seeds based on deep sequencing, and it contributes to a functional understanding of these miRNAs. PMID:24551031

Photoaffinity labeling in target- and binding-site identification

PubMed Central

Smith, Ewan; Collins, Ian

2015-01-01

Photoaffinity labeling (PAL) using a chemical probe to covalently bind its target in response to activation by light has become a frequently used tool in drug discovery for identifying new drug targets and molecular interactions, and for probing the location and structure of binding sites. Methods to identify the specific target proteins of hit molecules from phenotypic screens are highly valuable in early drug discovery. In this review, we summarize the principles of PAL including probe design and experimental techniques for in vitro and live cell investigations. We emphasize the need to optimize and validate probes and highlight examples of the successful application of PAL across multiple disease areas. PMID:25686004

Mistaken identity of a PCR target proposed for identification of Mycoplasma bovis and the effect of sequence variation on assay performance

USDA-ARS?s Scientific Manuscript database

Background. Mycoplasma bovis is an important cause of disease in cattle and has recently emerged as a primary disease agent in bison. Because the bacterium requires specialized growth conditions many diagnostic laboratories use PCR to replace or complement traditional isolation and identification ...

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.

Identification of "insoluble" red dyewoods by high performance liquid chromatography-photodiode array detection (HPLC-PDA) fingerprinting.

PubMed

Surowiec, Izabella; Nowik, Witold; Trojanowicz, Marek

2004-02-01

The paper describes a high performance liquid chromatography-UV/Vis spectrometry detection analytical approach to the identification of some redwood species of historical importance in textile dyeing. The group of extracted dyestuffs considered as "insoluble" because of their non-aqueous or alkaline extraction conditions is present in the wood of the Pterocarpus family and Baphia nitida species. First, the crude extracts of tinctorial and related species and their chromatographic fingerprints were studied. This part of work shows that some species not yet mentioned in the literature have potential dyeing properties. Subsequent experiments performed on the redwood cargo of a 200-year-old archaeological shipwreck allowed identification of the water-logged wood species. Furthermore, the different methods of dyestuff extraction used for dyeing according to traditional recipes and their impact on analytical results were studied. They show that standard recovery obtained by acid hydrolysis of dyestuff from dyed yarns is inadequate. Hence, alternative solvent-based procedures were proposed. The identification of species in textile threads then becomes possible. The applied approach was validated by analysis of dyed reference yarns with some indications of crude material extraction mode. The employed method of analysis seems to be useful for "insoluble" wood species identification in cultural heritage artifacts as well as for phytochemical purposes, despite the fact that very few detected color compounds were chemically identified.

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

Memory for found targets interferes with subsequent performance in multiple-target visual search.

PubMed

Cain, Matthew S; Mitroff, Stephen R

2013-10-01

Multiple-target visual searches--when more than 1 target can appear in a given search display--are commonplace in radiology, airport security screening, and the military. Whereas 1 target is often found accurately, additional targets are more likely to be missed in multiple-target searches. To better understand this decrement in 2nd-target detection, here we examined 2 potential forms of interference that can arise from finding a 1st target: interference from the perceptual salience of the 1st target (a now highly relevant distractor in a known location) and interference from a newly created memory representation for the 1st target. Here, we found that removing found targets from the display or making them salient and easily segregated color singletons improved subsequent search accuracy. However, replacing found targets with random distractor items did not improve subsequent search accuracy. Removing and highlighting found targets likely reduced both a target's visual salience and its memory load, whereas replacing a target removed its visual salience but not its representation in memory. Collectively, the current experiments suggest that the working memory load of a found target has a larger effect on subsequent search accuracy than does its perceptual salience. PsycINFO Database Record (c) 2013 APA, all rights reserved.

Signal-Noise Identification of Magnetotelluric Signals Using Fractal-Entropy and Clustering Algorithm for Targeted De-Noising

NASA Astrophysics Data System (ADS)

Li, Jin; Zhang, Xian; Gong, Jinzhe; Tang, Jingtian; Ren, Zhengyong; Li, Guang; Deng, Yanli; Cai, Jin

A new technique is proposed for signal-noise identification and targeted de-noising of Magnetotelluric (MT) signals. This method is based on fractal-entropy and clustering algorithm, which automatically identifies signal sections corrupted by common interference (square, triangle and pulse waves), enabling targeted de-noising and preventing the loss of useful information in filtering. To implement the technique, four characteristic parameters — fractal box dimension (FBD), higuchi fractal dimension (HFD), fuzzy entropy (FuEn) and approximate entropy (ApEn) — are extracted from MT time-series. The fuzzy c-means (FCM) clustering technique is used to analyze the characteristic parameters and automatically distinguish signals with strong interference from the rest. The wavelet threshold (WT) de-noising method is used only to suppress the identified strong interference in selected signal sections. The technique is validated through signal samples with known interference, before being applied to a set of field measured MT/Audio Magnetotelluric (AMT) data. Compared with the conventional de-noising strategy that blindly applies the filter to the overall dataset, the proposed method can automatically identify and purposefully suppress the intermittent interference in the MT/AMT signal. The resulted apparent resistivity-phase curve is more continuous and smooth, and the slow-change trend in the low-frequency range is more precisely reserved. Moreover, the characteristic of the target-filtered MT/AMT signal is close to the essential characteristic of the natural field, and the result more accurately reflects the inherent electrical structure information of the measured site.

Performance analysis of robust road sign identification

NASA Astrophysics Data System (ADS)

Ali, Nursabillilah M.; Mustafah, Y. M.; Rashid, N. K. A. M.

2013-12-01

This study describes performance analysis of a robust system for road sign identification that incorporated two stages of different algorithms. The proposed algorithms consist of HSV color filtering and PCA techniques respectively in detection and recognition stages. The proposed algorithms are able to detect the three standard types of colored images namely Red, Yellow and Blue. The hypothesis of the study is that road sign images can be used to detect and identify signs that are involved with the existence of occlusions and rotational changes. PCA is known as feature extraction technique that reduces dimensional size. The sign image can be easily recognized and identified by the PCA method as is has been used in many application areas. Based on the experimental result, it shows that the HSV is robust in road sign detection with minimum of 88% and 77% successful rate for non-partial and partial occlusions images. For successful recognition rates using PCA can be achieved in the range of 94-98%. The occurrences of all classes are recognized successfully is between 5% and 10% level of occlusions.

Optimization of a chemical identification algorithm

NASA Astrophysics Data System (ADS)

Chyba, Thomas H.; Fisk, Brian; Gunning, Christin; Farley, Kevin; Polizzi, Amber; Baughman, David; Simpson, Steven; Slamani, Mohamed-Adel; Almassy, Robert; Da Re, Ryan; Li, Eunice; MacDonald, Steve; Slamani, Ahmed; Mitchell, Scott A.; Pendell-Jones, Jay; Reed, Timothy L.; Emge, Darren

2010-04-01

A procedure to evaluate and optimize the performance of a chemical identification algorithm is presented. The Joint Contaminated Surface Detector (JCSD) employs Raman spectroscopy to detect and identify surface chemical contamination. JCSD measurements of chemical warfare agents, simulants, toxic industrial chemicals, interferents and bare surface backgrounds were made in the laboratory and under realistic field conditions. A test data suite, developed from these measurements, is used to benchmark algorithm performance throughout the improvement process. In any one measurement, one of many possible targets can be present along with interferents and surfaces. The detection results are expressed as a 2-category classification problem so that Receiver Operating Characteristic (ROC) techniques can be applied. The limitations of applying this framework to chemical detection problems are discussed along with means to mitigate them. Algorithmic performance is optimized globally using robust Design of Experiments and Taguchi techniques. These methods require figures of merit to trade off between false alarms and detection probability. Several figures of merit, including the Matthews Correlation Coefficient and the Taguchi Signal-to-Noise Ratio are compared. Following the optimization of global parameters which govern the algorithm behavior across all target chemicals, ROC techniques are employed to optimize chemical-specific parameters to further improve performance.

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.

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.

Identification of multi-targeted anti-migraine potential of nystatin and development of its brain targeted chitosan nanoformulation.

PubMed

Girotra, Priti; Thakur, Aman; Kumar, Ajay; Singh, Shailendra Kumar

2017-03-01

The complex pathophysiology involved in migraine necessitates the drug treatment to act on several receptors simultaneously. The present investigation was an attempt to discover the unidentified anti-migraine activity of the already marketed drugs. Shared featured pharmacophore modeling was employed for this purpose on six target receptors (β 2 adrenoceptor, Dopamine D 3 , 5HT 1B , TRPV1, iGluR5 kainate and CGRP), resulting in the generation of five shared featured pharmacophores, which were further subjected to virtual screening of the ligands obtained from Drugbank database. Molecular docking, performed on the obtained hit compounds from virtual screening, indicated nystatin to be the only active lead against the receptors iGluR5 kainate receptor (1VSO), CGRP (3N7R), β 2 adrenoceptor (3NYA) and Dopamine D 3 (3PBL) with a high binding energy of -11.1, -10.9, -10.2 and -12kcal/mole respectively. The anti-migraine activity of nystatin was then adjudged by fabricating its brain targeted chitosan nanoparticles. Its brain targeting efficacy, analyzed qualitatively by confocal laser scanning microscopy, demonstrated a significant amount of drug reaching the brain. The pharmacodynamic models on Swiss male albino mice revealed significant anti-migraine activity of the nanoformulation. The present study reports for the first time the therapeutic potential of nystatin in migraine management, hence opening avenues for its future exploration. Copyright © 2016 Elsevier B.V. All rights reserved.

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.

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

NASA Astrophysics Data System (ADS)

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

2017-01-01

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

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

PubMed Central

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

2017-01-01

Intrinsically disordered proteins (IDPs) are prevalent in eukaryotes, performing signaling and regulatory functions. Often associated with human diseases, they constitute drug-development targets. NUPR1 is a multifunctional IDP, over-expressed and involved in pancreatic ductal adenocarcinoma (PDAC) development. By screening 1120 FDA-approved compounds, fifteen candidates were selected, and their interactions with NUPR1 were characterized by experimental and simulation techniques. The protein remained disordered upon binding to all fifteen candidates. These compounds were tested in PDAC-derived cell-based assays, and all induced cell-growth arrest and senescence, reduced cell migration, and decreased chemoresistance, mimicking NUPR1-deficiency. The most effective compound completely arrested tumor development in vivo on xenografted PDAC-derived cells in mice. Besides reporting the discovery of a compound targeting an intact IDP and specifically active against PDAC, our study proves the possibility to target the ‘fuzzy’ interface of a protein that remains disordered upon binding to its natural biological partners or to selected drugs. PMID:28054562

Backloading in the sequential lineup prevents within-lineup criterion shifts that undermine eyewitness identification performance.

PubMed

Horry, Ruth; Palmer, Matthew A; Brewer, Neil

2012-12-01

Although the sequential lineup has been proposed as a means of protecting innocent suspects from mistaken identification, little is known about the importance of various aspects of the procedure. One potentially important detail is that witnesses should not know how many people are in the lineup. This is sometimes achieved by backloading the lineup so that witnesses believe that the lineup includes more photographs than it actually does. This study aimed to investigate the effect of backloading on witness decision making. A large sample (N = 833) of community-dwelling adults viewed a live "culprit" and then saw a target-present or target-absent sequential lineup. All lineups included 6 individuals, but the participants were told that the lineup included 6 photographs (nonbackloaded condition) or that the lineup included 12 or 30 photographs (backloaded conditions). The suspect either appeared early (Position 2) or late (Position 6) in the lineup. Innocent suspects placed in Position 6 were chosen more frequently by participants in the nonbackloaded condition than in either backloaded condition. Additionally, when the lineup was not backloaded, foil identification rates increased from Positions 3 to 5, suggesting a gradually shifting response criterion. The results suggest that backloading encourages participants to adopt a more conservative response criterion, and it reduces or eliminates the tendency for the criterion to become more lenient over the course of the lineup. The results underscore the absolute importance of ensuring that witnesses who view sequential lineups are unaware of the number of individuals to be seen.

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.

Identification of Five Novel Salmonella Typhi-Specific Genes as Markers for Diagnosis of Typhoid Fever Using Single-Gene Target PCR Assays.

PubMed

Goay, Yuan Xin; Chin, Kai Ling; Tan, Clarissa Ling Ling; Yeoh, Chiann Ying; Ja'afar, Ja'afar Nuhu; Zaidah, Abdul Rahman; Chinni, Suresh Venkata; Phua, Kia Kien

2016-01-01

Salmonella Typhi ( S . Typhi) causes typhoid fever which is a disease characterised by high mortality and morbidity worldwide. In order to curtail the transmission of this highly infectious disease, identification of new markers that can detect the pathogen is needed for development of sensitive and specific diagnostic tests. In this study, genomic comparison of S . Typhi with other enteric pathogens was performed, and 6 S . Typhi genes, that is, STY0201, STY0307, STY0322, STY0326, STY2020, and STY2021, were found to be specific in silico . Six PCR assays each targeting a unique gene were developed to test the specificity of these genes in vitro . The diagnostic sensitivities and specificities of each assay were determined using 39 S . Typhi, 62 non-Typhi Salmonella , and 10 non- Salmonella clinical isolates. The results showed that 5 of these genes, that is, STY0307, STY0322, STY0326, STY2020, and STY2021, demonstrated 100% sensitivity (39/39) and 100% specificity (0/72). The detection limit of the 5 PCR assays was 32 pg for STY0322, 6.4 pg for STY0326, STY2020, and STY2021, and 1.28 pg for STY0307. In conclusion, 5 PCR assays using STY0307, STY0322, STY0326, STY2020, and STY2021 were developed and found to be highly specific at single-gene target resolution for diagnosis of typhoid fever.

Identification and verification of critical performance dimensions. Phase 1 of the systematic process redesign of drug distribution.

PubMed

Colen, Hadewig B; Neef, Cees; Schuring, Roel W

2003-06-01

Worldwide patient safety has become a major social policy problem for healthcare organisations. As in other organisations, the patients in our hospital also suffer from an inadequate distribution process, as becomes clear from incident reports involving medication errors. Medisch Spectrum Twente is a top primary-care, clinical, teaching hospital. The hospital pharmacy takes care of 1070 internal beds and 1120 beds in an affiliated psychiatric hospital and nursing homes. In the beginning of 1999, our pharmacy group started a large interdisciplinary research project to develop a safe, effective and efficient drug distribution system by using systematic process redesign. The process redesign includes both organisational and technological components. This article describes the identification and verification of critical performance dimensions for the design of drug distribution processes in hospitals (phase 1 of the systematic process redesign of drug distribution). Based on reported errors and related causes, we suggested six generic performance domains. To assess the role of the performance dimensions, we used three approaches: flowcharts, interviews with stakeholders and review of the existing performance using time studies and medication error studies. We were able to set targets for costs, quality of information, responsiveness, employee satisfaction, and degree of innovation. We still have to establish what drug distribution system, in respect of quality and cost-effectiveness, represents the best and most cost-effective way of preventing medication errors. We intend to develop an evaluation model, using the critical performance dimensions as a starting point. This model can be used as a simulation template to compare different drug distribution concepts in order to define the differences in quality and cost-effectiveness.

The development of high-performance alkali-hybrid polarized He 3 targets for electron scattering

DOE PAGES

Singh, Jaideep T.; Dolph, Peter A.M.; Tobias, William Al; ...

2015-05-01

We present the development of high-performance polarized ³He targets for use in electron scattering experiments that utilize the technique of alkali-hybrid spin-exchange optical pumping. We include data obtained during the characterization of 24 separate target cells, each of which was constructed while preparing for one of four experiments at Jefferson Laboratory in Newport News, Virginia. The results presented here document dramatic improvement in the performance of polarized ³He targets, as well as the target properties and operating parameters that made those improvements possible. Included in our measurements were determinations of the so-called X-factors that quantify a temperature-dependent and as-yet poorly understood spin-relaxation mechanism that limits the maximum achievable ³He polarization to well under 100%. The presence of this spin-relaxation mechanism was clearly evident in our data. We also present results from a simulation of the alkali-hydrid spin-exchange optical pumping process that was developed to provide guidance in the design of these targets. Good agreement with actual performance was obtained by including details such as off-resonant optical pumping. Now benchmarked against experimental data, the simulation is useful for the design of future targets. Included in our results is a measurement of the K- ³He spin-exchange rate coefficientmore » $$k^\\mathrm{K}_\\mathrm{se} = \\left ( 7.46 \\pm 0.62 \\right )\\!\\times\\!10^{-20}\\ \\mathrm{cm^3/s}$$ over the temperature range 503 K to 563 K.« less

Performance of target detection algorithm in compressive sensing miniature ultraspectral imaging compressed sensing system

NASA Astrophysics Data System (ADS)

Gedalin, Daniel; Oiknine, Yaniv; August, Isaac; Blumberg, Dan G.; Rotman, Stanley R.; Stern, Adrian

2017-04-01

Compressive sensing theory was proposed to deal with the high quantity of measurements demanded by traditional hyperspectral systems. Recently, a compressive spectral imaging technique dubbed compressive sensing miniature ultraspectral imaging (CS-MUSI) was presented. This system uses a voltage controlled liquid crystal device to create multiplexed hyperspectral cubes. We evaluate the utility of the data captured using the CS-MUSI system for the task of target detection. Specifically, we compare the performance of the matched filter target detection algorithm in traditional hyperspectral systems and in CS-MUSI multiplexed hyperspectral cubes. We found that the target detection algorithm performs similarly in both cases, despite the fact that the CS-MUSI data is up to an order of magnitude less than that in conventional hyperspectral cubes. Moreover, the target detection is approximately an order of magnitude faster in CS-MUSI data.

SuperTarget goes quantitative: update on drug–target interactions

PubMed Central

Hecker, Nikolai; Ahmed, Jessica; von Eichborn, Joachim; Dunkel, Mathias; Macha, Karel; Eckert, Andreas; Gilson, Michael K.; Bourne, Philip E.; Preissner, Robert

2012-01-01

There are at least two good reasons for the on-going interest in drug–target interactions: first, drug-effects can only be fully understood by considering a complex network of interactions to multiple targets (so-called off-target effects) including metabolic and signaling pathways; second, it is crucial to consider drug-target-pathway relations for the identification of novel targets for drug development. To address this on-going need, we have developed a web-based data warehouse named SuperTarget, which integrates drug-related information associated with medical indications, adverse drug effects, drug metabolism, pathways and Gene Ontology (GO) terms for target proteins. At present, the updated database contains >6000 target proteins, which are annotated with >330 000 relations to 196 000 compounds (including approved drugs); the vast majority of interactions include binding affinities and pointers to the respective literature sources. The user interface provides tools for drug screening and target similarity inclusion. A query interface enables the user to pose complex queries, for example, to find drugs that target a certain pathway, interacting drugs that are metabolized by the same cytochrome P450 or drugs that target proteins within a certain affinity range. SuperTarget is available at http://bioinformatics.charite.de/supertarget. PMID:22067455

Using the QCM Biosensor-Based T7 Phage Display Combined with Bioinformatics Analysis for Target Identification of Bioactive Small Molecule.

PubMed

Takakusagi, Yoichi; Takakusagi, Kaori; Sugawara, Fumio; Sakaguchi, Kengo

2018-01-01

Identification of target proteins that directly bind to bioactive small molecule is of great interest in terms of clarifying the mode of action of the small molecule as well as elucidating the biological phenomena at the molecular level. Of the experimental technologies available, T7 phage display allows comprehensive screening of small molecule-recognizing amino acid sequence from the peptide libraries displayed on the T7 phage capsid. Here, we describe the T7 phage display strategy that is combined with quartz-crystal microbalance (QCM) biosensor for affinity selection platform and bioinformatics analysis for small molecule-recognizing short peptides. This method dramatically enhances efficacy and throughput of the screening for small molecule-recognizing amino acid sequences without repeated rounds of selection. Subsequent execution of bioinformatics programs allows combinatorial and comprehensive target protein discovery of small molecules with its binding site, regardless of protein sample insolubility, instability, or inaccessibility of the fixed small molecules to internally located binding site on larger target proteins when conventional proteomics approaches are used.

Impact of 'stretch' targets for cardiovascular disease management within a local pay-for-performance programme.

PubMed

Pape, Utz J; Huckvale, Kit; Car, Josip; Majeed, Azeem; Millett, Christopher

2015-01-01

Pay-for-performance programs are often aimed to improve the management of chronic diseases. We evaluate the impact of a local pay for performance programme (QOF+), which rewarded financially more ambitious quality targets ('stretch targets') than those used nationally in the Quality and Outcomes Framework (QOF). We focus on targets for intermediate outcomes in patients with cardiovascular disease and diabetes. A difference-in-difference approach is used to compare practice level achievements before and after the introduction of the local pay for performance program. In addition, we analysed patient-level data on exception reporting and intermediate outcomes utilizing an interrupted time series analysis. The local pay for performance program led to significantly higher target achievements (hypertension: p-value <0.001, coronary heart disease: p-values <0.001, diabetes: p-values <0.061, stroke: p-values <0.003). However, the increase was driven by higher rates of exception reporting (hypertension: p-value <0.001, coronary heart disease: p-values <0.03, diabetes: p-values <0.05) in patients with all conditions except for stroke. Exception reporting allows practitioners to exclude patients from target calculations if certain criteria are met, e.g. informed dissent of the patient for treatment. There were no statistically significant improvements in mean blood pressure, cholesterol or HbA1c levels. Thus, achievement of higher payment thresholds in the local pay for performance scheme was mainly attributed to increased exception reporting by practices with no discernable improvements in overall clinical quality. Hence, active monitoring of exception reporting should be considered when setting more ambitious quality targets. More generally, the study suggests a trade-off between additional incentive for better care and monitoring costs.

Cancer Transcriptome Dataset Analysis: Comparing Methods of Pathway and Gene Regulatory Network-Based Cluster Identification.

PubMed

Nam, Seungyoon

2017-04-01

Cancer transcriptome analysis is one of the leading areas of Big Data science, biomarker, and pharmaceutical discovery, not to forget personalized medicine. Yet, cancer transcriptomics and postgenomic medicine require innovation in bioinformatics as well as comparison of the performance of available algorithms. In this data analytics context, the value of network generation and algorithms has been widely underscored for addressing the salient questions in cancer pathogenesis. Analysis of cancer trancriptome often results in complicated networks where identification of network modularity remains critical, for example, in delineating the "druggable" molecular targets. Network clustering is useful, but depends on the network topology in and of itself. Notably, the performance of different network-generating tools for network cluster (NC) identification has been little investigated to date. Hence, using gastric cancer (GC) transcriptomic datasets, we compared two algorithms for generating pathway versus gene regulatory network-based NCs, showing that the pathway-based approach better agrees with a reference set of cancer-functional contexts. Finally, by applying pathway-based NC identification to GC transcriptome datasets, we describe cancer NCs that associate with candidate therapeutic targets and biomarkers in GC. These observations collectively inform future research on cancer transcriptomics, drug discovery, and rational development of new analysis tools for optimal harnessing of omics data.

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

Identification of Mucorales From Clinical Specimens: A 4-Year Experience in a Single Institution

PubMed Central

Yang, Mina; Lee, Jang Ho; Kim, Young-Kwon; Ki, Chang-Seok

2016-01-01

Mucormycosis, a fatal opportunistic infection in immunocompromised hosts, is caused by fungi belonging to the order Mucorales. Early diagnosis based on exact identification and multidisciplinary treatments is critical. However, identification of Mucorales fungi is difficult and often delayed, resulting in poor prognosis. This study aimed to compare the results of phenotypic and molecular identification of 12 Mucorales isolates collected from 4-yr-accumulated data. All isolates were identified on the basis of phenotypic characteristics such as growth rate, colony morphology, and reproductive structures. PCR and direct sequencing were performed to target internal transcribed spacer (ITS) and/or D1/D2 regions. Target DNA sequencing identified five Lichtheimia isolates, two Rhizopus microsporus isolates, two Rhizomucor pusillus isolates, one Cunninghamella bertholletiae isolate, one Mucor fragilis isolate, and one Syncephalastrum racemosum isolate. Five of the 12 (41.7%) isolates were incorrectly identified on the basis of phenotypic identification. DNA sequencing showed that of these five isolates, two were Lichtheimia isolates, one was Mucor isolate, one was Rhizomucor isolate, and one was Rhizopus microspores. All the isolates were identified at the species level by ITS and/or D1/D2 analyses. Phenotypic differentiation and identification of Mucorales is difficult because different Mucorales share similar morphology. Our results indicate that the molecular methods employed in this study are valuable for identifying Mucorales. PMID:26522761

Identification of mucorales from clinical specimens: a 4-year experience in a single institution.

PubMed

Yang, Mina; Lee, Jang Ho; Kim, Young Kwon; Ki, Chang Seok; Huh, Hee Jae; Lee, Nam Yong

2016-01-01

Mucormycosis, a fatal opportunistic infection in immunocompromised hosts, is caused by fungi belonging to the order Mucorales. Early diagnosis based on exact identification and multidisciplinary treatments is critical. However, identification of Mucorales fungi is difficult and often delayed, resulting in poor prognosis. This study aimed to compare the results of phenotypic and molecular identification of 12 Mucorales isolates collected from 4-yr-accumulated data. All isolates were identified on the basis of phenotypic characteristics such as growth rate, colony morphology, and reproductive structures. PCR and direct sequencing were performed to target internal transcribed spacer (ITS) and/or D1/D2 regions. Target DNA sequencing identified five Lichtheimia isolates, two Rhizopus microsporus isolates, two Rhizomucor pusillus isolates, one Cunninghamella bertholletiae isolate, one Mucor fragilis isolate, and one Syncephalastrum racemosum isolate. Five of the 12 (41.7%) isolates were incorrectly identified on the basis of phenotypic identification. DNA sequencing showed that of these five isolates, two were Lichtheimia isolates, one was Mucor isolate, one was Rhizomucor isolate, and one was Rhizopus microspores. All the isolates were identified at the species level by ITS and/or D1/D2 analyses. Phenotypic differentiation and identification of Mucorales is difficult because different Mucorales share similar morphology. Our results indicate that the molecular methods employed in this study are valuable for identifying Mucorales.

Comparative genomics identification of a novel set of temporally regulated hedgehog target genes in the retina.

PubMed

McNeill, Brian; Perez-Iratxeta, Carol; Mazerolle, Chantal; Furimsky, Marosh; Mishina, Yuji; Andrade-Navarro, Miguel A; Wallace, Valerie A

2012-03-01

The hedgehog (Hh) signaling pathway is involved in numerous developmental and adult processes with many links to cancer. In vertebrates, the activity of the Hh pathway is mediated primarily through three Gli transcription factors (Gli1, 2 and 3) that can serve as transcriptional activators or repressors. The identification of Gli target genes is essential for the understanding of the Hh-mediated processes. We used a comparative genomics approach using the mouse and human genomes to identify 390 genes that contained conserved Gli binding sites. RT-qPCR validation of 46 target genes in E14.5 and P0.5 retinal explants revealed that Hh pathway activation resulted in the modulation of 30 of these targets, 25 of which demonstrated a temporal regulation. Further validation revealed that the expression of Bok, FoxA1, Sox8 and Wnt7a was dependent upon Sonic Hh (Shh) signaling in the retina and their regulation is under positive and negative controls by Gli2 and Gli3, respectively. We also show using chromatin immunoprecipitation that Gli2 binds to the Sox8 promoter, suggesting that Sox8 is an Hh-dependent direct target of Gli2. Finally, we demonstrate that the Hh pathway also modulates the expression of Sox9 and Sox10, which together with Sox8 make up the SoxE group. Previously, it has been shown that Hh and SoxE group genes promote Müller glial cell development in the retina. Our data are consistent with the possibility for a role of SoxE group genes downstream of Hh signaling on Müller cell development. Crown Copyright © 2012. Published by Elsevier Inc. All rights reserved.

Simultaneous identification and DNA barcoding of six Eimeria species infecting turkeys using PCR primers targeting the mitochondrial cytochrome c oxidase subunit I (mtCOI) locus.

PubMed

Hafeez, Mian A; Shivaramaiah, Srichaitanya; Dorsey, Kristi Moore; Ogedengbe, Mosun E; El-Sherry, Shiem; Whale, Julia; Cobean, Julie; Barta, John R

2015-05-01

Species-specific PCR primers targeting the mitochondrial cytochrome c oxidase subunit I (mtCOI) locus were generated that allow for the specific identification of the most common Eimeria species infecting turkeys (i.e., Eimeria adenoeides, Eimeria meleagrimitis, Eimeria gallopavonis, Eimeria meleagridis, Eimeria dispersa, and Eimeria innocua). PCR reaction chemistries were optimized with respect to divalent cation (MgCl2) and dNTP concentrations, as well as PCR cycling conditions (particularly anneal temperature for primers). Genomic DNA samples from single oocyst-derived lines of six Eimeria species were tested to establish specificity and sensitivity of these newly designed primer pairs. A mixed 60-ng total DNA sample containing 10 ng of each of the six Eimeria species was used as DNA template to demonstrate specific amplification of the correct product using each of the species-specific primer pairs. Ten nanograms of each of the five non-target Eimeria species was pooled to provide a non-target, control DNA sample suitable to test the specificity of each primer pair. The amplifications of the COI region with species-specific primer pairs from pooled samples yielded products of expected sizes (209 to 1,012 bp) and no amplification of non-target Eimeria sp. DNA was detected using the non-target, control DNA samples. These primer pairs specific for Eimeria spp. of turkeys did not amplify any of the seven Eimeria species infecting chickens. The newly developed PCR primers can be used as a diagnostic tool capable of specifically identifying six turkey Eimeria species; additionally, sequencing of the PCR amplification products yields sequence-based genotyping data suitable for identification and molecular phylogenetics.

Performance of optimized McRAPD in identification of 9 yeast species frequently isolated from patient samples: potential for automation.

PubMed

Trtkova, Jitka; Pavlicek, Petr; Ruskova, Lenka; Hamal, Petr; Koukalova, Dagmar; Raclavsky, Vladislav

2009-11-10

Rapid, easy, economical and accurate species identification of yeasts isolated from clinical samples remains an important challenge for routine microbiological laboratories, because susceptibility to antifungal agents, probability to develop resistance and ability to cause disease vary in different species. To overcome the drawbacks of the currently available techniques we have recently proposed an innovative approach to yeast species identification based on RAPD genotyping and termed McRAPD (Melting curve of RAPD). Here we have evaluated its performance on a broader spectrum of clinically relevant yeast species and also examined the potential of automated and semi-automated interpretation of McRAPD data for yeast species identification. A simple fully automated algorithm based on normalized melting data identified 80% of the isolates correctly. When this algorithm was supplemented by semi-automated matching of decisive peaks in first derivative plots, 87% of the isolates were identified correctly. However, a computer-aided visual matching of derivative plots showed the best performance with average 98.3% of the accurately identified isolates, almost matching the 99.4% performance of traditional RAPD fingerprinting. Since McRAPD technique omits gel electrophoresis and can be performed in a rapid, economical and convenient way, we believe that it can find its place in routine identification of medically important yeasts in advanced diagnostic laboratories that are able to adopt this technique. It can also serve as a broad-range high-throughput technique for epidemiological surveillance.

Automatic identification approach for high-performance liquid chromatography-multiple reaction monitoring fatty acid global profiling.

PubMed

Tie, Cai; Hu, Ting; Jia, Zhi-Xin; Zhang, Jin-Lan

2015-08-18

Fatty acids (FAs) are a group of lipid molecules that are essential to organisms. As potential biomarkers for different diseases, FAs have attracted increasing attention from both biological researchers and the pharmaceutical industry. A sensitive and accurate method for globally profiling and identifying FAs is required for biomarker discovery. The high selectivity and sensitivity of high-performance liquid chromatography-multiple reaction monitoring (HPLC-MRM) gives it great potential to fulfill the need to identify FAs from complicated matrices. This paper developed a new approach for global FA profiling and identification for HPLC-MRM FA data mining. Mathematical models for identifying FAs were simulated using the isotope-induced retention time (RT) shift (IRS) and peak area ratios between parallel isotope peaks for a series of FA standards. The FA structures were predicated using another model based on the RT and molecular weight. Fully automated FA identification software was coded using the Qt platform based on these mathematical models. Different samples were used to verify the software. A high identification efficiency (greater than 75%) was observed when 96 FA species were identified in plasma. This FAs identification strategy promises to accelerate FA research and applications.

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.

The High Momentum Particle IDentification (HMPID) detector PID performance and its contribution to the ALICE physics program

NASA Astrophysics Data System (ADS)

Volpe, Giacomo; ALICE Collaboration

2017-12-01

The ALICE apparatus is dedicated to study the properties of strongly interacting matter under extremely high temperature and energy density conditions. For this, enhanced particle identification (PID) capabilities are required. Among the PID ALICE detectors, the ALICE-HMPID (High Momentum Particle IDentification) detector is devoted to the identification of charged hadrons, exploiting the Cherenkov effect. It consists of seven identical RICH modules, with liquid C6F14 as Cherenkov radiator (n ≈1.298 at λ=175 nm). Photon and charged particle detection is performed by a MWPC, coupled with a pad segmented CsI coated photo-cathode. The total CsI active area is 10.3 m2. The HMPID provides 3 sigma separation for pions and kaons up to pT = 3 GeV / c and for kaons and (anti-)protons up to pT = 5 GeV / c . A review of the HMPID PID performance, in particular in the challenging central Pb-Pb collisions, and its contribution to the ALICE physics program, using the LHC RUN1 (2010-2013) and RUN2 (2015) data, are presented.

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.

Parallel Reaction Monitoring: A Targeted Experiment Performed Using High Resolution and High Mass Accuracy Mass Spectrometry

PubMed Central

Rauniyar, Navin

2015-01-01

The parallel reaction monitoring (PRM) assay has emerged as an alternative method of targeted quantification. The PRM assay is performed in a high resolution and high mass accuracy mode on a mass spectrometer. This review presents the features that make PRM a highly specific and selective method for targeted quantification using quadrupole-Orbitrap hybrid instruments. In addition, this review discusses the label-based and label-free methods of quantification that can be performed with the targeted approach. PMID:26633379

Flexible Fusion Structure-Based Performance Optimization Learning for Multisensor Target Tracking

PubMed Central

Ge, Quanbo; Wei, Zhongliang; Cheng, Tianfa; Chen, Shaodong; Wang, Xiangfeng

2017-01-01

Compared with the fixed fusion structure, the flexible fusion structure with mixed fusion methods has better adjustment performance for the complex air task network systems, and it can effectively help the system to achieve the goal under the given constraints. Because of the time-varying situation of the task network system induced by moving nodes and non-cooperative target, and limitations such as communication bandwidth and measurement distance, it is necessary to dynamically adjust the system fusion structure including sensors and fusion methods in a given adjustment period. Aiming at this, this paper studies the design of a flexible fusion algorithm by using an optimization learning technology. The purpose is to dynamically determine the sensors’ numbers and the associated sensors to take part in the centralized and distributed fusion processes, respectively, herein termed sensor subsets selection. Firstly, two system performance indexes are introduced. Especially, the survivability index is presented and defined. Secondly, based on the two indexes and considering other conditions such as communication bandwidth and measurement distance, optimization models for both single target tracking and multi-target tracking are established. Correspondingly, solution steps are given for the two optimization models in detail. Simulation examples are demonstrated to validate the proposed algorithms. PMID:28481243

Light Video Game Play is Associated with Enhanced Visual Processing of Rapid Serial Visual Presentation Targets.

PubMed

Howard, Christina J; Wilding, Robert; Guest, Duncan

2017-02-01

There is mixed evidence that video game players (VGPs) may demonstrate better performance in perceptual and attentional tasks than non-VGPs (NVGPs). The rapid serial visual presentation task is one such case, where observers respond to two successive targets embedded within a stream of serially presented items. We tested light VGPs (LVGPs) and NVGPs on this task. LVGPs were better at correct identification of second targets whether they were also attempting to respond to the first target. This performance benefit seen for LVGPs suggests enhanced visual processing for briefly presented stimuli even with only very moderate game play. Observers were less accurate at discriminating the orientation of a second target within the stream if it occurred shortly after presentation of the first target, that is to say, they were subject to the attentional blink (AB). We find no evidence for any reduction in AB in LVGPs compared with NVGPs.

Blended shared control utilizing online identification : Regulating grasping forces of a surrogate surgical grasper.

PubMed

Stephens, Trevor K; Kong, Nathan J; Dockter, Rodney L; O'Neill, John J; Sweet, Robert M; Kowalewski, Timothy M

2018-06-01

Surgical robots are increasingly common, yet routine tasks such as tissue grasping remain potentially harmful with high occurrences of tissue crush injury due to the lack of force feedback from the grasper. This work aims to investigate whether a blended shared control framework which utilizes real-time identification of the object being grasped as part of the feedback may help address the prevalence of tissue crush injury in robotic surgeries. This work tests the proposed shared control framework and tissue identification algorithm on a custom surrogate surgical robotic grasping setup. This scheme utilizes identification of the object being grasped as part of the feedback to regulate to a desired force. The blended shared control is arbitrated between human and an implicit force controller based on a computed confidence in the identification of the grasped object. The online identification is performed using least squares based on a nonlinear tissue model. Testing was performed on five silicone tissue surrogates. Twenty grasps were conducted, with half of the grasps performed under manual control and half of the grasps performed with the proposed blended shared control, to test the efficacy of the control scheme. The identification method resulted in an average of 95% accuracy across all time samples of all tissue grasps using a full leave-grasp-out cross-validation. There was an average convergence time of [Formula: see text] ms across all training grasps for all tissue surrogates. Additionally, there was a reduction in peak forces induced during grasping for all tissue surrogates when applying blended shared control online. The blended shared control using online identification more successfully regulated grasping forces to the desired target force when compared with manual control. The preliminary work on this surrogate setup for surgical grasping merits further investigation on real surgical tools and with real human tissues.

GAMUT: GPU accelerated microRNA analysis to uncover target genes through CUDA-miRanda

PubMed Central

2014-01-01

Background Non-coding sequences such as microRNAs have important roles in disease processes. Computational microRNA target identification (CMTI) is becoming increasingly important since traditional experimental methods for target identification pose many difficulties. These methods are time-consuming, costly, and often need guidance from computational methods to narrow down candidate genes anyway. However, most CMTI methods are computationally demanding, since they need to handle not only several million query microRNA and reference RNA pairs, but also several million nucleotide comparisons within each given pair. Thus, the need to perform microRNA identification at such large scale has increased the demand for parallel computing. Methods Although most CMTI programs (e.g., the miRanda algorithm) are based on a modified Smith-Waterman (SW) algorithm, the existing parallel SW implementations (e.g., CUDASW++ 2.0/3.0, SWIPE) are unable to meet this demand in CMTI tasks. We present CUDA-miRanda, a fast microRNA target identification algorithm that takes advantage of massively parallel computing on Graphics Processing Units (GPU) using NVIDIA's Compute Unified Device Architecture (CUDA). CUDA-miRanda specifically focuses on the local alignment of short (i.e., ≤ 32 nucleotides) sequences against longer reference sequences (e.g., 20K nucleotides). Moreover, the proposed algorithm is able to report multiple alignments (up to 191 top scores) and the corresponding traceback sequences for any given (query sequence, reference sequence) pair. Results Speeds over 5.36 Giga Cell Updates Per Second (GCUPs) are achieved on a server with 4 NVIDIA Tesla M2090 GPUs. Compared to the original miRanda algorithm, which is evaluated on an Intel Xeon E5620@2.4 GHz CPU, the experimental results show up to 166 times performance gains in terms of execution time. In addition, we have verified that the exact same targets were predicted in both CUDA-miRanda and the original mi

Construction Project Performance Improvement through Radio Frequency Identification Technology Application on a Project Supply Chain

ERIC Educational Resources Information Center

Wang, Heng

2017-01-01

Construction project productivity typically lags other industries and it has been the focus of numerous studies in order to improve the project performance. This research investigated the application of Radio Frequency Identification (RFID) technology on construction projects' supply chain and determined that RFID technology can improve the…

Identification of the feedforward component in manual control with predictable target signals.

PubMed

Drop, Frank M; Pool, Daan M; Damveld, Herman J; van Paassen, Marinus M; Mulder, Max

2013-12-01

In the manual control of a dynamic system, the human controller (HC) often follows a visible and predictable reference path. Compared with a purely feedback control strategy, performance can be improved by making use of this knowledge of the reference. The operator could effectively introduce feedforward control in conjunction with a feedback path to compensate for errors, as hypothesized in literature. However, feedforward behavior has never been identified from experimental data, nor have the hypothesized models been validated. This paper investigates human control behavior in pursuit tracking of a predictable reference signal while being perturbed by a quasi-random multisine disturbance signal. An experiment was done in which the relative strength of the target and disturbance signals were systematically varied. The anticipated changes in control behavior were studied by means of an ARX model analysis and by fitting three parametric HC models: two different feedback models and a combined feedforward and feedback model. The ARX analysis shows that the experiment participants employed control action on both the error and the target signal. The control action on the target was similar to the inverse of the system dynamics. Model fits show that this behavior can be modeled best by the combined feedforward and feedback model.

Species-specific identification of Dekkera/Brettanomyces yeasts by fluorescently labeled DNA probes targeting the 26S rRNA.

PubMed

Röder, Christoph; König, Helmut; Fröhlich, Jürgen

2007-09-01

Sequencing of the complete 26S rRNA genes of all Dekkera/Brettanomyces species colonizing different beverages revealed the potential for a specific primer and probe design to support diagnostic PCR approaches and FISH. By analysis of the complete 26S rRNA genes of all five currently known Dekkera/Brettanomyces species (Dekkera bruxellensis, D. anomala, Brettanomyces custersianus, B. nanus and B. naardenensis), several regions with high nucleotide sequence variability yet distinct from the D1/D2 domains were identified. FISH species-specific probes targeting the 26S rRNA gene's most variable regions were designed. Accessibility of probe targets for hybridization was facilitated by the construction of partially complementary 'side'-labeled probes, based on secondary structure models of the rRNA sequences. The specificity and routine applicability of the FISH-based method for yeast identification were tested by analyzing different wine isolates. Investigation of the prevalence of Dekkera/Brettanomyces yeasts in the German viticultural regions Wonnegau, Nierstein and Bingen (Rhinehesse, Rhineland-Palatinate) resulted in the isolation of 37 D. bruxellensis strains from 291 wine samples.

Developing Performance Cost Index Targets for ASHRAE Standard 90.1 Appendix G – Performance Rating Method

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

Rosenberg, Michael I.; Hart, Philip R.

2016-02-16

Appendix G, the Performance Rating Method in ASHRAE Standard 90.1 has been updated to make two significant changes for the 2016 edition, to be published in October of 2016. First, it allows Appendix G to be used as a third path for compliance with the standard in addition to rating beyond code building performance. This prevents modelers from having to develop separate building models for code compliance and beyond code programs. Using this new version of Appendix G to show compliance with the 2016 edition of the standard, the proposed building design needs to have a performance cost index (PCI)more » less than targets shown in a new table based on building type and climate zone. The second change is that the baseline design is now fixed at a stable level of performance set approximately equal to the 2004 code. Rather than changing the stringency of the baseline with each subsequent edition of the standard, compliance with new editions will simply require a reduced PCI (a PCI of zero is a net-zero building). Using this approach, buildings of any era can be rated using the same method. The intent is that any building energy code or beyond code program can use this methodology and merely set the appropriate PCI target for their needs. This report discusses the process used to set performance criteria for compliance with ASHRAE Standard 90.1-2016 and suggests a method for demonstrating compliance with other codes and beyond code programs.« less

Quantitative performance targets by using balanced scorecard system: application to waste management and public administration.

PubMed

Mendes, Paula; Nunes, Luis Miguel; Teixeira, Margarida Ribau

2014-09-01

This article demonstrates how decision-makers can be guided in the process of defining performance target values in the balanced scorecard system. We apply a method based on sensitivity analysis with Monte Carlo simulation to the municipal solid waste management system in Loulé Municipality (Portugal). The method includes two steps: sensitivity analysis of performance indicators to identify those performance indicators with the highest impact on the balanced scorecard model outcomes; and sensitivity analysis of the target values for the previously identified performance indicators. Sensitivity analysis shows that four strategic objectives (IPP1: Comply with the national waste strategy; IPP4: Reduce nonrenewable resources and greenhouse gases; IPP5: Optimize the life-cycle of waste; and FP1: Meet and optimize the budget) alone contribute 99.7% of the variability in overall balanced scorecard value. Thus, these strategic objectives had a much stronger impact on the estimated balanced scorecard outcome than did others, with the IPP1 and the IPP4 accounting for over 55% and 22% of the variance in overall balanced scorecard value, respectively. The remaining performance indicators contribute only marginally. In addition, a change in the value of a single indicator's target value made the overall balanced scorecard value change by as much as 18%. This may lead to involuntarily biased decisions by organizations regarding performance target-setting, if not prevented with the help of methods such as that proposed and applied in this study. © The Author(s) 2014.

Benchmark data sets for structure-based computational target prediction.

PubMed

Schomburg, Karen T; Rarey, Matthias

2014-08-25

Structure-based computational target prediction methods identify potential targets for a bioactive compound. Methods based on protein-ligand docking so far face many challenges, where the greatest probably is the ranking of true targets in a large data set of protein structures. Currently, no standard data sets for evaluation exist, rendering comparison and demonstration of improvements of methods cumbersome. Therefore, we propose two data sets and evaluation strategies for a meaningful evaluation of new target prediction methods, i.e., a small data set consisting of three target classes for detailed proof-of-concept and selectivity studies and a large data set consisting of 7992 protein structures and 72 drug-like ligands allowing statistical evaluation with performance metrics on a drug-like chemical space. Both data sets are built from openly available resources, and any information needed to perform the described experiments is reported. We describe the composition of the data sets, the setup of screening experiments, and the evaluation strategy. Performance metrics capable to measure the early recognition of enrichments like AUC, BEDROC, and NSLR are proposed. We apply a sequence-based target prediction method to the large data set to analyze its content of nontrivial evaluation cases. The proposed data sets are used for method evaluation of our new inverse screening method iRAISE. The small data set reveals the method's capability and limitations to selectively distinguish between rather similar protein structures. The large data set simulates real target identification scenarios. iRAISE achieves in 55% excellent or good enrichment a median AUC of 0.67 and RMSDs below 2.0 Å for 74% and was able to predict the first true target in 59 out of 72 cases in the top 2% of the protein data set of about 8000 structures.

Characterizing the effects of droplines on target acquisition performance on a 3-D perspective display

NASA Technical Reports Server (NTRS)

Liao, Min-Ju; Johnson, Walter W.

2004-01-01

The present study investigated the effects of droplines on target acquisition performance on a 3-D perspective display in which participants were required to move a cursor into a target cube as quickly as possible. Participants' performance and coordination strategies were characterized using both Fitts' law and acquisition patterns of the 3 viewer-centered target display dimensions (azimuth, elevation, and range). Participants' movement trajectories were recorded and used to determine movement times for acquisitions of the entire target and of each of its display dimensions. The goodness of fit of the data to a modified Fitts function varied widely among participants, and the presence of droplines did not have observable impacts on the goodness of fit. However, droplines helped participants navigate via straighter paths and particularly benefited range dimension acquisition. A general preference for visually overlapping the target with the cursor prior to capturing the target was found. Potential applications of this research include the design of interactive 3-D perspective displays in which fast and accurate selection and manipulation of content residing at multiple ranges may be a challenge.

The role of driver age in performance and attention allocation effects of roadway sign count, format and familiarity.

PubMed

Zahabi, Maryam; Machado, Patricia; Pankok, Carl; Lau, Mei Ying; Liao, Yi-Fan; Hummer, Joseph; Rasdorf, William; Kaber, David B

2017-09-01

White-on-blue logo signs are used to inform drivers of food, gas, lodging, and attraction businesses at highway interchanges. In this study, 60 drivers were asked to look for food and attraction targets on logo signs while driving in a realistic freeway simulation. The objective of the study was to quantify effects of the number of sign panels (six vs. nine), logo familiarity (familiar vs. unfamiliar), logo format (text vs. pictorial), and driver age (young, middle, and elderly) on performance, attention allocation and target identification accuracy. Results revealed elderly drivers to exhibit worse performance in comparison to middle-age and young groups even though they adopted a more conservative driving strategy. There was no significant effect of the number of panels, logo familiarity, and logo format on driver performance or attention allocation. In target identification, drivers were more accurate with familiar or text-based panels appearing in six-panel signs. Copyright © 2017 Elsevier Ltd. All rights reserved.

Targeting of PHOX2B expression allows the identification of drugs effective in counteracting neuroblastoma cell growth

PubMed Central

Zanni, Eleonora Di; Bianchi, Giovanna; Ravazzolo, Roberto; Raffaghello, Lizzia; Ceccherini, Isabella; Bachetti, Tiziana

2017-01-01

The pathogenic role of the PHOX2B gene in neuroblastoma is indicated by heterozygous mutations in neuroblastoma patients and by gene overexpression in both neuroblastoma cell lines and tumor samples. PHOX2B encodes a transcription factor which is crucial for the correct development and differentiation of sympathetic neurons. PHOX2B overexpression is considered a prognostic marker for neuroblastoma and it is also used by clinicians to monitor minimal residual disease. Furthermore, it has been observed that neuronal differentiation in neuroblastoma is dependent on down-regulation of PHOX2B expression, which confirms that PHOX2B expression may be considered a target in neuroblastoma. Here, PHOX2B promoter or 3′ untranslated region were used as molecular targets in an in vitro high-throughput approach that led to the identification of molecules able to decrease PHOX2B expression at transcriptional and likely even at post-transcriptional levels. Further functional investigations carried out on PHOX2B mRNA levels and biological consequences, such as neuroblastoma cell apoptosis and growth, showed that chloroquine and mycophenolate mofetil are most promising agents for neuroblastoma therapy based on down-regulation of PHOX2B expression. Finally, a strong correlation between the effect of drugs in terms of down-regulation of PHOX2B expression and of biological consequences in neuroblastoma cells confirms the role of PHOX2B as a potential molecular target in neuroblastoma. PMID:29069774

Action-specific judgment, not perception: Fitts' law performance is related to estimates of target width only when participants are given a performance score.

PubMed

Zelaznik, Howard N; Forney, Laura A

2016-08-01

Proponents of the action-specific account of perception and action posit that participants perceive their environment relative to their capabilities. For example, softball players who batted well judge the ball as being larger compared to players who did not hit as well. In the present study, we examined this issue in the context of a well-known speed-accuracy movement task that can be examined in the laboratory, repetitive Fitts aiming. In the Fitts task, a performer moved as quickly and as accurately as possible between two targets, D units of distance apart (between 2.5 and 20.0 cm) and of W width (1.0 cm or less). In the Fitts task, we posited that individuals do not have access to performance quality. Thus, we asked whether individual differences in Fitts task performance was related to perception of target width. If Fitts task performance is related to perception of target width, then the action-specific effect on perception does not require explicit knowledge of performance and, furthermore, these effects reside during on-line visual control of the task. We show that only when subjects were provided with a performance score was there a relation between Fitts task performance and target width judgment error. We interpret this result to mean that action-specific effects do not occur during perceptual processing of the task, but action-specific effects are the result of postperformance evaluation processes.

Genomic identification of direct target genes of LEAFY

PubMed Central

William, Dilusha A.; Su, Yanhui; Smith, Michael R.; Lu, Meina; Baldwin, Don A.; Wagner, Doris

2004-01-01

The switch from vegetative to reproductive development in plants necessitates a switch in the developmental program of the descendents of the stem cells in the shoot apical meristem. Genetic and molecular investigations have demonstrated that the plant-specific transcription factor and meristem identity regulator LEAFY (LFY) controls this developmental transition by inducing expression of a second transcription factor, APETALA1, and by regulating the expression of additional, as yet unknown, genes. Here we show that the additional LFY targets include the APETALA1-related factor, CAULI-FLOWER, as well as three transcription factors and two putative signal transduction pathway components. These genes are up-regulated by LFY even when protein synthesis is inhibited and, hence, appear to be direct targets of LFY. Supporting this conclusion, cis-regulatory regions upstream of these genes are bound by LFY in vivo. The newly identified LFY targets likely initiate the transcriptional changes that are required for the switch from vegetative to reproductive development in Arabidopsis. PMID:14736918

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2010 CFR

2010-04-01

... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

21 CFR 886.1880 - Fusion and stereoscopic target.

Code of Federal Regulations, 2011 CFR

2011-04-01

... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Fusion and stereoscopic target. 886.1880 Section... (CONTINUED) MEDICAL DEVICES OPHTHALMIC DEVICES Diagnostic Devices § 886.1880 Fusion and stereoscopic target. (a) Identification. A fusion and stereoscopic target is a device intended for use as a viewing object...

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.

Influence of transactive memory on perceived performance, job satisfaction and identification in anaesthesia teams.

PubMed

Michinov, E; Olivier-Chiron, E; Rusch, E; Chiron, B

2008-03-01

There is an increasing awareness in the medical community that human factors are involved in effectiveness of anaesthesia teams. Communication and coordination between physicians and nurses seems to play a crucial role in maintaining a good level of performance under time pressure, particularly for anaesthesia teams, who are confronted with uncertainty, rapid changes in the environment, and multi-tasking. The aim of this study was to examine the relationship between a specific form of implicit coordination--the transactive memory system--and perceptions of team effectiveness and work attitudes such as job satisfaction and team identification. A cross-sectional study was conducted among 193 nurse and physician anaesthetists from eight French public hospitals. The questionnaire included some measures of transactive memory system (coordination, specialization, and credibility components), perception of team effectiveness, and work attitudes (Minnesota Job Satisfaction Questionnaire, team identification scale). The questionnaire was designed to be filled anonymously, asking only biographical data relating to sex, age, status, and tenure. Hierarchical multiple regression analyses revealed as predicted that transactive memory system predicted members' perceptions of team effectiveness, and also affective outcomes such as job satisfaction and team identification. Moreover, the results demonstrated that transactive memory processes, and especially the coordination component, were a better predictor of teamwork perceptions than socio-demographic (i.e. gender or status) or contextual variables (i.e. tenure and size of team). These findings provided empirical evidence of the existence of a transactive memory system among real anaesthesia teams, and highlight the need to investigate whether transactive memory is actually linked with objective measures of performance.

Multiple independent identification decisions: a method of calibrating eyewitness identifications.

PubMed

Pryke, Sean; Lindsay, R C L; Dysart, Jennifer E; Dupuis, Paul

2004-02-01

Two experiments (N = 147 and N = 90) explored the use of multiple independent lineups to identify a target seen live. In Experiment 1, simultaneous face, body, and sequential voice lineups were used. In Experiment 2, sequential face, body, voice, and clothing lineups were used. Both studies demonstrated that multiple identifications (by the same witness) from independent lineups of different features are highly diagnostic of suspect guilt (G. L. Wells & R. C. L. Lindsay, 1980). The number of suspect and foil selections from multiple independent lineups provides a powerful method of calibrating the accuracy of eyewitness identification. Implications for use of current methods are discussed. ((c) 2004 APA, all rights reserved)

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.

Anthropometric and performance measures for the development of a talent detection and identification model in youth handball.

PubMed

Mohamed, Hasan; Vaeyens, Roel; Matthys, Stijn; Multael, Marc; Lefevre, Johan; Lenoir, Matthieu; Philppaerts, Renaat

2009-02-01

The first part of this study examined in which basic morphological and fitness measures Under-14 (n=34) and Under-16 (n=47) male youth handball players differ from reference samples of the same age (n=430 and n=570, respectively). To help develop a talent identification model, the second part of the study investigated which specific morphological and performance measures describe differences between elite (n=18) and non-elite (n=29) Under-16 youth handball players. The results showed that Under-16 handball players were significantly taller than the reference group; this was not the case in the Under-14 age group. Physical fitness in handball players was significantly better than in the reference groups. Multivariate analysis of covariance (maturation and chronological age as covariates) showed that the Under-16 elite players were heavier and had greater muscle circumferences than their non-elite peers. Elite players scored significantly better on strength, speed and agility, and cardiorespiratory endurance but not on balance, upper limb speed, flexibility or upper body muscular endurance. Maturation was a significant covariate in anthropometric measures but not in physical performance. Discriminant analysis between elite and non-elite players revealed that height, running speed, and agility are important parameters for talent identification. Specific anthropometric measures, in addition to some performance measures, are useful for talent identification in youth handball.

Reduced Performance of Prey Targeting in Pit Vipers with Contralaterally Occluded Infrared and Visual Senses

PubMed Central

Chen, Qin; Deng, Huanhuan; Brauth, Steven E.; Ding, Li; Tang, Yezhong

2012-01-01

Both visual and infrared (IR) senses are utilized in prey targeting by pit vipers. Visual and IR inputs project to the contralateral optic tectum where they activate both multimodal and bimodal neurons. A series of ocular and pit organ occlusion experiments using the short-tailed pit viper (Gloydius brevicaudus) were conducted to investigate the role of visual and IR information during prey targeting. Compared with unoccluded controls, snakes with either both eyes or pit organs occluded performed more poorly in hunting prey although such subjects still captured prey on 75% of trials. Subjects with one eye and one pit occluded on the same side of the face performed as well as those with bilateral occlusion although these subjects showed a significant targeting angle bias toward the unoccluded side. Performance was significantly poorer when only a single eye or pit was available. Interestingly, when one eye and one pit organ were occluded on opposite sides of the face, performance was poorest, the snakes striking prey on no more than half the trials. These results indicate that, visual and infrared information are both effective in prey targeting in this species, although interference between the two modalities occurs if visual and IR information is restricted to opposite sides of the brain. PMID:22606229

P41IDENTIFICATION OF GLIOMA SPECIFIC APTAMER TARGETS

PubMed Central

Arora, Mohit; Alder, Jane; Lawrence, Clare; Davis, Charles; Dawson, Tim; Hall, Greg; Shaw, Lisa

2014-01-01

INTRODUCTION: Aptamers are in vitro generated DNA and RNA sequences which are randomly created as a library, with multiple permutations and combinations. These are then exposed to the target structure against which we want an aptamer ‘selected’ using Sequential Enumeration of Ligands by Exponential enrichment (SELEX). METHOD: Commercially available glioma and glial cell lines and in-house generated primary glioma cultures were used. Modified aptamers based on published sequences against glioma cell lines and newly generated sequences were used in the project to identify their binding targets. Cy3 or biotin- conjugated aptamers were incubated with live glioma cell cultures and imaged using confocal or light microscopy.To determine the target ligand, aptamers were then reacted with glial cell lysate and subjected to precipitation using streptavidin agarose beads and SDS polyacrylamide electrophoresis. Proteins were analysed by mass spectroscopy. RESULTS: Known and unknown aptamer protein ligands were co-precipitated. Ku70, Ku80 were precipitated along with nucleolin and related proteins. CONCLUSION: The aptamer has shown preferential binding to glioma cells and could act as a delivery system for therapeutic payloads. The aptamer targets Ku70 and Ku80, which are known to be over expressed in other forms of cancer but their role in gliomagenesis has not been fully elucidated. Other novel proteins have also been identified. Thus the aptamer co-precipitation technique has identified potential glioma biomarkers that may be of clinical significance.

In Vitro Evaluation of Molecular Tumor Targets in Nuclear Medicine: Immunohistochemistry Is One Option, but Under Which Conditions?

PubMed

Reubi, Jean Claude

2017-12-01

The identification of new molecular targets for diagnostic and therapeutic applications using in vitro methods is an important challenge in nuclear medicine. One such method is immunohistochemistry, increasingly popular because it is easy to perform. This review presents the case for conducting receptor immunohistochemistry to evaluate potential molecular targets in human tumor tissue sections. The focus is on the immunohistochemistry of G-protein-coupled receptors, one of the largest families of cell surface proteins, representing a major class of drug targets and thus playing an important role in nuclear medicine. This review identifies common pitfalls and challenges and provides guidelines on performing such immunohistochemical studies. An appropriate validation of the target is a prerequisite for developing robust and informative new molecular probes. © 2017 by the Society of Nuclear Medicine and Molecular Imaging.

Rapid and accurate identification of Mycobacterium tuberculosis complex and common non-tuberculous mycobacteria by multiplex real-time PCR targeting different housekeeping genes.

PubMed

Nasr Esfahani, Bahram; Rezaei Yazdi, Hadi; Moghim, Sharareh; Ghasemian Safaei, Hajieh; Zarkesh Esfahani, Hamid

2012-11-01

Rapid and accurate identification of mycobacteria isolates from primary culture is important due to timely and appropriate antibiotic therapy. Conventional methods for identification of Mycobacterium species based on biochemical tests needs several weeks and may remain inconclusive. In this study, a novel multiplex real-time PCR was developed for rapid identification of Mycobacterium genus, Mycobacterium tuberculosis complex (MTC) and the most common non-tuberculosis mycobacteria species including M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and the M. gordonae in three reaction tubes but under same PCR condition. Genetic targets for primer designing included the 16S rDNA gene, the dnaJ gene, the gyrB gene and internal transcribed spacer (ITS). Multiplex real-time PCR was setup with reference Mycobacterium strains and was subsequently tested with 66 clinical isolates. Results of multiplex real-time PCR were analyzed with melting curves and melting temperature (T (m)) of Mycobacterium genus, MTC, and each of non-tuberculosis Mycobacterium species were determined. Multiplex real-time PCR results were compared with amplification and sequencing of 16S-23S rDNA ITS for identification of Mycobacterium species. Sensitivity and specificity of designed primers were each 100 % for MTC, M. abscessus, M. fortuitum, M. avium complex, M. kansasii, and M. gordonae. Sensitivity and specificity of designed primer for genus Mycobacterium was 96 and 100 %, respectively. According to the obtained results, we conclude that this multiplex real-time PCR with melting curve analysis and these novel primers can be used for rapid and accurate identification of genus Mycobacterium, MTC, and the most common non-tuberculosis Mycobacterium species.

Cue combination in a combined feature contrast detection and figure identification task.

PubMed

Meinhardt, Günter; Persike, Malte; Mesenholl, Björn; Hagemann, Cordula

2006-11-01

Target figures defined by feature contrast in spatial frequency, orientation or both cues had to be detected in Gabor random fields and their shape had to be identified in a dual task paradigm. Performance improved with increasing feature contrast and was strongly correlated among both tasks. Subjects performed significantly better with combined cues than with single cues. The improvement due to cue summation was stronger than predicted by the assumption of independent feature specific mechanisms, and increased with the performance level achieved with single cues until it was limited by ceiling effects. Further, cue summation was also strongly correlated among tasks: when there was benefit due to the additional cue in feature contrast detection, there was also benefit in figure identification. For the same performance level achieved with single cues, cue summation was generally larger in figure identification than in feature contrast detection, indicating more benefit when processes of shape and surface formation are involved. Our results suggest that cue combination improves spatial form completion and figure-ground segregation in noisy environments, and therefore leads to more stable object vision.

Performance Evaluation of the Verigene Gram-Positive and Gram-Negative Blood Culture Test for Direct Identification of Bacteria and Their Resistance Determinants from Positive Blood Cultures in Hong Kong

PubMed Central

Siu, Gilman K. H.; Chen, Jonathan H. K.; Ng, T. K.; Lee, Rodney A.; Fung, Kitty S. C.; To, Sabrina W. C.; Wong, Barry K. C.; Cheung, Sherman; Wong, Ivan W. F.; Tam, Marble M. P.; Lee, Swing S. W.; Yam, W. C.

2015-01-01

Background A multicenter study was conducted to evaluate the diagnostic performance and the time to identifcation of the Verigene Blood Culture Test, the BC-GP and BC-GN assays, to identify both Gram-positive and Gram-negative bacteria and their drug resistance determinants directly from positive blood cultures collected in Hong Kong. Methods and Results A total of 364 blood cultures were prospectively collected from four public hospitals, in which 114 and 250 cultures yielded Gram-positive and Gram-negative bacteria, and were tested with the BC-GP and BC-GN assay respectively. The overall identification agreement for Gram-positive and Gram-negative bacteria were 89.6% and 90.5% in monomicrobial cultures and 62.5% and 53.6% in polymicrobial cultures, respectively. The sensitivities for most genus/species achieved at least 80% except Enterococcus spp. (60%), K.oxytoca (0%), K.pneumoniae (69.2%), whereas the specificities for all targets ranged from 98.9% to 100%. Of note, 50% (7/14) cultures containing K.pneumoniae that were missed by the BC-GN assay were subsequently identified as K.variicola. Approximately 5.5% (20/364) cultures contained non-target organisms, of which Aeromonas spp. accounted for 25% and are of particular concern. For drug resistance determination, the Verigene test showed 100% sensitivity for identification of MRSA, VRE and carbapenem resistant Acinetobacter, and 84.4% for ESBL-producing Enterobacteriaceae based on the positive detection of mecA, vanA, bla OXA and bla CTXM respectively. Conclusion Overall, the Verigene test provided acceptable accuracy for identification of bacteria and resistance markers with a range of turnaround time 40.5 to 99.2 h faster than conventional methods in our region. PMID:26431434