Sample records for target recognition domain

  1. Interactive object recognition assistance: an approach to recognition starting from target objects

    NASA Astrophysics Data System (ADS)

    Geisler, Juergen; Littfass, Michael

    1999-07-01

    Recognition of target objects in remotely sensed imagery required detailed knowledge about the target object domain as well as about mapping properties of the sensing system. The art of object recognition is to combine both worlds appropriately and to provide models of target appearance with respect to sensor characteristics. Common approaches to support interactive object recognition are either driven from the sensor point of view and address the problem of displaying images in a manner adequate to the sensing system. Or they focus on target objects and provide exhaustive encyclopedic information about this domain. Our paper discusses an approach to assist interactive object recognition based on knowledge about target objects and taking into account the significance of object features with respect to characteristics of the sensed imagery, e.g. spatial and spectral resolution. An `interactive recognition assistant' takes the image analyst through the interpretation process by indicating step-by-step the respectively most significant features of objects in an actual set of candidates. The significance of object features is expressed by pregenerated trees of significance, and by the dynamic computation of decision relevance for every feature at each step of the recognition process. In the context of this approach we discuss the question of modeling and storing the multisensorial/multispectral appearances of target objects and object classes as well as the problem of an adequate dynamic human-machine-interface that takes into account various mental models of human image interpretation.

  2. Phosphotyrosine recognition domains: the typical, the atypical and the versatile

    PubMed Central

    2012-01-01

    SH2 domains are long known prominent players in the field of phosphotyrosine recognition within signaling protein networks. However, over the years they have been joined by an increasing number of other protein domain families that can, at least with some of their members, also recognise pTyr residues in a sequence-specific context. This superfamily of pTyr recognition modules, which includes substantial fractions of the PTB domains, as well as much smaller, or even single member fractions like the HYB domain, the PKCδ and PKCθ C2 domains and RKIP, represents a fascinating, medically relevant and hence intensely studied part of the cellular signaling architecture of metazoans. Protein tyrosine phosphorylation clearly serves a plethora of functions and pTyr recognition domains are used in a similarly wide range of interaction modes, which encompass, for example, partner protein switching, tandem recognition functionalities and the interaction with catalytically active protein domains. If looked upon closely enough, virtually no pTyr recognition and regulation event is an exact mirror image of another one in the same cell. Thus, the more we learn about the biology and ultrastructural details of pTyr recognition domains, the more does it become apparent that nature cleverly combines and varies a few basic principles to generate a sheer endless number of sophisticated and highly effective recognition/regulation events that are, under normal conditions, elegantly orchestrated in time and space. This knowledge is also valuable when exploring pTyr reader domains as diagnostic tools, drug targets or therapeutic reagents to combat human diseases. PMID:23134684

  3. Specific and Modular Binding Code for Cytosine Recognition in Pumilio/FBF (PUF) RNA-binding Domains

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

    Dong, Shuyun; Wang, Yang; Cassidy-Amstutz, Caleb

    2011-10-28

    Pumilio/fem-3 mRNA-binding factor (PUF) proteins possess a recognition code for bases A, U, and G, allowing designed RNA sequence specificity of their modular Pumilio (PUM) repeats. However, recognition side chains in a PUM repeat for cytosine are unknown. Here we report identification of a cytosine-recognition code by screening random amino acid combinations at conserved RNA recognition positions using a yeast three-hybrid system. This C-recognition code is specific and modular as specificity can be transferred to different positions in the RNA recognition sequence. A crystal structure of a modified PUF domain reveals specific contacts between an arginine side chain and themore » cytosine base. We applied the C-recognition code to design PUF domains that recognize targets with multiple cytosines and to generate engineered splicing factors that modulate alternative splicing. Finally, we identified a divergent yeast PUF protein, Nop9p, that may recognize natural target RNAs with cytosine. This work deepens our understanding of natural PUF protein target recognition and expands the ability to engineer PUF domains to recognize any RNA sequence.« less

  4. Domain repertoires as a tool to derive protein recognition rules.

    PubMed

    Zucconi, A; Panni, S; Paoluzi, S; Castagnoli, L; Dente, L; Cesareni, G

    2000-08-25

    Several approaches, some of which are described in this issue, have been proposed to assemble a complete protein interaction map. These are often based on high throughput methods that explore the ability of each gene product to bind any other element of the proteome of the organism. Here we propose that a large number of interactions can be inferred by revealing the rules underlying recognition specificity of a small number (a few hundreds) of families of protein recognition modules. This can be achieved through the construction and characterization of domain repertoires. A domain repertoire is assembled in a combinatorial fashion by allowing each amino acid position in the binding site of a given protein recognition domain to vary to include all the residues allowed at that position in the domain family. The repertoire is then searched by phage display techniques with any target of interest and from the primary structure of the binding site of the selected domains one derives rules that are used to infer the formation of complexes between natural proteins in the cell.

  5. An Exemplar-Based Multi-View Domain Generalization Framework for Visual Recognition.

    PubMed

    Niu, Li; Li, Wen; Xu, Dong; Cai, Jianfei

    2018-02-01

    In this paper, we propose a new exemplar-based multi-view domain generalization (EMVDG) framework for visual recognition by learning robust classifier that are able to generalize well to arbitrary target domain based on the training samples with multiple types of features (i.e., multi-view features). In this framework, we aim to address two issues simultaneously. First, the distribution of training samples (i.e., the source domain) is often considerably different from that of testing samples (i.e., the target domain), so the performance of the classifiers learnt on the source domain may drop significantly on the target domain. Moreover, the testing data are often unseen during the training procedure. Second, when the training data are associated with multi-view features, the recognition performance can be further improved by exploiting the relation among multiple types of features. To address the first issue, considering that it has been shown that fusing multiple SVM classifiers can enhance the domain generalization ability, we build our EMVDG framework upon exemplar SVMs (ESVMs), in which a set of ESVM classifiers are learnt with each one trained based on one positive training sample and all the negative training samples. When the source domain contains multiple latent domains, the learnt ESVM classifiers are expected to be grouped into multiple clusters. To address the second issue, we propose two approaches under the EMVDG framework based on the consensus principle and the complementary principle, respectively. Specifically, we propose an EMVDG_CO method by adding a co-regularizer to enforce the cluster structures of ESVM classifiers on different views to be consistent based on the consensus principle. Inspired by multiple kernel learning, we also propose another EMVDG_MK method by fusing the ESVM classifiers from different views based on the complementary principle. In addition, we further extend our EMVDG framework to exemplar-based multi-view domain

  6. A Fast, Efficient Domain Adaptation Technique for Cross-Domain Electroencephalography(EEG)-Based Emotion Recognition.

    PubMed

    Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou

    2017-05-03

    Electroencephalography (EEG)-based emotion recognition is an important element in psychiatric health diagnosis for patients. However, the underlying EEG sensor signals are always non-stationary if they are sampled from different experimental sessions or subjects. This results in the deterioration of the classification performance. Domain adaptation methods offer an effective way to reduce the discrepancy of marginal distribution. However, for EEG sensor signals, both marginal and conditional distributions may be mismatched. In addition, the existing domain adaptation strategies always require a high level of additional computation. To address this problem, a novel strategy named adaptive subspace feature matching (ASFM) is proposed in this paper in order to integrate both the marginal and conditional distributions within a unified framework (without any labeled samples from target subjects). Specifically, we develop a linear transformation function which matches the marginal distributions of the source and target subspaces without a regularization term. This significantly decreases the time complexity of our domain adaptation procedure. As a result, both marginal and conditional distribution discrepancies between the source domain and unlabeled target domain can be reduced, and logistic regression (LR) can be applied to the new source domain in order to train a classifier for use in the target domain, since the aligned source domain follows a distribution which is similar to that of the target domain. We compare our ASFM method with six typical approaches using a public EEG dataset with three affective states: positive, neutral, and negative. Both offline and online evaluations were performed. The subject-to-subject offline experimental results demonstrate that our component achieves a mean accuracy and standard deviation of 80.46% and 6.84%, respectively, as compared with a state-of-the-art method, the subspace alignment auto-encoder (SAAE), which achieves values

  7. A Fast, Efficient Domain Adaptation Technique for Cross-Domain Electroencephalography(EEG)-Based Emotion Recognition

    PubMed Central

    Chai, Xin; Wang, Qisong; Zhao, Yongping; Li, Yongqiang; Liu, Dan; Liu, Xin; Bai, Ou

    2017-01-01

    Electroencephalography (EEG)-based emotion recognition is an important element in psychiatric health diagnosis for patients. However, the underlying EEG sensor signals are always non-stationary if they are sampled from different experimental sessions or subjects. This results in the deterioration of the classification performance. Domain adaptation methods offer an effective way to reduce the discrepancy of marginal distribution. However, for EEG sensor signals, both marginal and conditional distributions may be mismatched. In addition, the existing domain adaptation strategies always require a high level of additional computation. To address this problem, a novel strategy named adaptive subspace feature matching (ASFM) is proposed in this paper in order to integrate both the marginal and conditional distributions within a unified framework (without any labeled samples from target subjects). Specifically, we develop a linear transformation function which matches the marginal distributions of the source and target subspaces without a regularization term. This significantly decreases the time complexity of our domain adaptation procedure. As a result, both marginal and conditional distribution discrepancies between the source domain and unlabeled target domain can be reduced, and logistic regression (LR) can be applied to the new source domain in order to train a classifier for use in the target domain, since the aligned source domain follows a distribution which is similar to that of the target domain. We compare our ASFM method with six typical approaches using a public EEG dataset with three affective states: positive, neutral, and negative. Both offline and online evaluations were performed. The subject-to-subject offline experimental results demonstrate that our component achieves a mean accuracy and standard deviation of 80.46% and 6.84%, respectively, as compared with a state-of-the-art method, the subspace alignment auto-encoder (SAAE), which achieves values

  8. Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute.

    PubMed

    Miyoshi, Tomohiro; Ito, Kosuke; Murakami, Ryo; Uchiumi, Toshio

    2016-06-21

    Argonaute proteins are key players in the gene silencing mechanisms mediated by small nucleic acids in all domains of life from bacteria to eukaryotes. However, little is known about the Argonaute protein that recognizes guide RNA/target DNA. Here, we determine the 2 Å crystal structure of Rhodobacter sphaeroides Argonaute (RsAgo) in a complex with 18-nucleotide guide RNA and its complementary target DNA. The heteroduplex maintains Watson-Crick base-pairing even in the 3'-region of the guide RNA between the N-terminal and PIWI domains, suggesting a recognition mode by RsAgo for stable interaction with the target strand. In addition, the MID/PIWI interface of RsAgo has a system that specifically recognizes the 5' base-U of the guide RNA, and the duplex-recognition loop of the PAZ domain is important for the DNA silencing activity. Furthermore, we show that Argonaute discriminates the nucleic acid type (RNA/DNA) by recognition of the duplex structure of the seed region.

  9. Structural basis for the recognition of guide RNA and target DNA heteroduplex by Argonaute

    PubMed Central

    Miyoshi, Tomohiro; Ito, Kosuke; Murakami, Ryo; Uchiumi, Toshio

    2016-01-01

    Argonaute proteins are key players in the gene silencing mechanisms mediated by small nucleic acids in all domains of life from bacteria to eukaryotes. However, little is known about the Argonaute protein that recognizes guide RNA/target DNA. Here, we determine the 2 Å crystal structure of Rhodobacter sphaeroides Argonaute (RsAgo) in a complex with 18-nucleotide guide RNA and its complementary target DNA. The heteroduplex maintains Watson–Crick base-pairing even in the 3′-region of the guide RNA between the N-terminal and PIWI domains, suggesting a recognition mode by RsAgo for stable interaction with the target strand. In addition, the MID/PIWI interface of RsAgo has a system that specifically recognizes the 5′ base-U of the guide RNA, and the duplex-recognition loop of the PAZ domain is important for the DNA silencing activity. Furthermore, we show that Argonaute discriminates the nucleic acid type (RNA/DNA) by recognition of the duplex structure of the seed region. PMID:27325485

  10. Use of the recognition heuristic depends on the domain's recognition validity, not on the recognition validity of selected sets of objects.

    PubMed

    Pohl, Rüdiger F; Michalkiewicz, Martha; Erdfelder, Edgar; Hilbig, Benjamin E

    2017-07-01

    According to the recognition-heuristic theory, decision makers solve paired comparisons in which one object is recognized and the other not by recognition alone, inferring that recognized objects have higher criterion values than unrecognized ones. However, success-and thus usefulness-of this heuristic depends on the validity of recognition as a cue, and adaptive decision making, in turn, requires that decision makers are sensitive to it. To this end, decision makers could base their evaluation of the recognition validity either on the selected set of objects (the set's recognition validity), or on the underlying domain from which the objects were drawn (the domain's recognition validity). In two experiments, we manipulated the recognition validity both in the selected set of objects and between domains from which the sets were drawn. The results clearly show that use of the recognition heuristic depends on the domain's recognition validity, not on the set's recognition validity. In other words, participants treat all sets as roughly representative of the underlying domain and adjust their decision strategy adaptively (only) with respect to the more general environment rather than the specific items they are faced with.

  11. The Vanderbilt Expertise Test Reveals Domain-General and Domain-Specific Sex Effects in Object Recognition

    PubMed Central

    McGugin, Rankin W.; Richler, Jennifer J.; Herzmann, Grit; Speegle, Magen; Gauthier, Isabel

    2012-01-01

    Individual differences in face recognition are often contrasted with differences in object recognition using a single object category. Likewise, individual differences in perceptual expertise for a given object domain have typically been measured relative to only a single category baseline. In Experiment 1, we present a new test of object recognition, the Vanderbilt Expertise Test (VET), which is comparable in methods to the Cambridge Face Memory Task (CFMT) but uses eight different object categories. Principal component analysis reveals that the underlying structure of the VET can be largely explained by two independent factors, which demonstrate good reliability and capture interesting sex differences inherent in the VET structure. In Experiment 2, we show how the VET can be used to separate domain-specific from domain-general contributions to a standard measure of perceptual expertise. While domain-specific contributions are found for car matching for both men and women and for plane matching in men, women in this sample appear to use more domain-general strategies to match planes. In Experiment 3, we use the VET to demonstrate that holistic processing of faces predicts face recognition independently of general object recognition ability, which has a sex-specific contribution to face recognition. Overall, the results suggest that the VET is a reliable and valid measure of object recognition abilities and can measure both domain-general skills and domain-specific expertise, which were both found to depend on the sex of observers. PMID:22877929

  12. Adapting Word Embeddings from Multiple Domains to Symptom Recognition from Psychiatric Notes

    PubMed Central

    Zhang, Yaoyun; Li, Hee-Jin; Wang, Jingqi; Cohen, Trevor; Roberts, Kirk; Xu, Hua

    2018-01-01

    Mental health is increasingly recognized an important topic in healthcare. Information concerning psychiatric symptoms is critical for the timely diagnosis of mental disorders, as well as for the personalization of interventions. However, the diversity and sparsity of psychiatric symptoms make it challenging for conventional natural language processing techniques to automatically extract such information from clinical text. To address this problem, this study takes the initiative to use and adapt word embeddings from four source domains – intensive care, biomedical literature, Wikipedia and Psychiatric Forum – to recognize symptoms in the target domain of psychiatry. We investigated four different approaches including 1) only using word embeddings of the source domain, 2) directly combining data of the source and target to generate word embeddings, 3) assigning different weights to word embeddings, and 4) retraining the word embedding model of the source domain using a corpus of the target domain. To the best of our knowledge, this is the first work of adapting multiple word embeddings of external domains to improve psychiatric symptom recognition in clinical text. Experimental results showed that the last two approaches outperformed the baseline methods, indicating the effectiveness of our new strategies to leverage embeddings from other domains. PMID:29888086

  13. Image-algebraic design of multispectral target recognition algorithms

    NASA Astrophysics Data System (ADS)

    Schmalz, Mark S.; Ritter, Gerhard X.

    1994-06-01

    In this paper, we discuss methods for multispectral ATR (Automated Target Recognition) of small targets that are sensed under suboptimal conditions, such as haze, smoke, and low light levels. In particular, we discuss our ongoing development of algorithms and software that effect intelligent object recognition by selecting ATR filter parameters according to ambient conditions. Our algorithms are expressed in terms of IA (image algebra), a concise, rigorous notation that unifies linear and nonlinear mathematics in the image processing domain. IA has been implemented on a variety of parallel computers, with preprocessors available for the Ada and FORTRAN languages. An image algebra C++ class library has recently been made available. Thus, our algorithms are both feasible implementationally and portable to numerous machines. Analyses emphasize the aspects of image algebra that aid the design of multispectral vision algorithms, such as parameterized templates that facilitate the flexible specification of ATR filters.

  14. Face recognition in the thermal infrared domain

    NASA Astrophysics Data System (ADS)

    Kowalski, M.; Grudzień, A.; Palka, N.; Szustakowski, M.

    2017-10-01

    Biometrics refers to unique human characteristics. Each unique characteristic may be used to label and describe individuals and for automatic recognition of a person based on physiological or behavioural properties. One of the most natural and the most popular biometric trait is a face. The most common research methods on face recognition are based on visible light. State-of-the-art face recognition systems operating in the visible light spectrum achieve very high level of recognition accuracy under controlled environmental conditions. Thermal infrared imagery seems to be a promising alternative or complement to visible range imaging due to its relatively high resistance to illumination changes. A thermal infrared image of the human face presents its unique heat-signature and can be used for recognition. The characteristics of thermal images maintain advantages over visible light images, and can be used to improve algorithms of human face recognition in several aspects. Mid-wavelength or far-wavelength infrared also referred to as thermal infrared seems to be promising alternatives. We present the study on 1:1 recognition in thermal infrared domain. The two approaches we are considering are stand-off face verification of non-moving person as well as stop-less face verification on-the-move. The paper presents methodology of our studies and challenges for face recognition systems in the thermal infrared domain.

  15. Protein-targeted corona phase molecular recognition

    PubMed Central

    Bisker, Gili; Dong, Juyao; Park, Hoyoung D.; Iverson, Nicole M.; Ahn, Jiyoung; Nelson, Justin T.; Landry, Markita P.; Kruss, Sebastian; Strano, Michael S.

    2016-01-01

    Corona phase molecular recognition (CoPhMoRe) uses a heteropolymer adsorbed onto and templated by a nanoparticle surface to recognize a specific target analyte. This method has not yet been extended to macromolecular analytes, including proteins. Herein we develop a variant of a CoPhMoRe screening procedure of single-walled carbon nanotubes (SWCNT) and use it against a panel of human blood proteins, revealing a specific corona phase that recognizes fibrinogen with high selectivity. In response to fibrinogen binding, SWCNT fluorescence decreases by >80% at saturation. Sequential binding of the three fibrinogen nodules is suggested by selective fluorescence quenching by isolated sub-domains and validated by the quenching kinetics. The fibrinogen recognition also occurs in serum environment, at the clinically relevant fibrinogen concentrations in the human blood. These results open new avenues for synthetic, non-biological antibody analogues that recognize biological macromolecules, and hold great promise for medical and clinical applications. PMID:26742890

  16. 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

  17. Combining high-speed SVM learning with CNN feature encoding for real-time target recognition in high-definition video for ISR missions

    NASA Astrophysics Data System (ADS)

    Kroll, Christine; von der Werth, Monika; Leuck, Holger; Stahl, Christoph; Schertler, Klaus

    2017-05-01

    For Intelligence, Surveillance, Reconnaissance (ISR) missions of manned and unmanned air systems typical electrooptical payloads provide high-definition video data which has to be exploited with respect to relevant ground targets in real-time by automatic/assisted target recognition software. Airbus Defence and Space is developing required technologies for real-time sensor exploitation since years and has combined the latest advances of Deep Convolutional Neural Networks (CNN) with a proprietary high-speed Support Vector Machine (SVM) learning method into a powerful object recognition system with impressive results on relevant high-definition video scenes compared to conventional target recognition approaches. This paper describes the principal requirements for real-time target recognition in high-definition video for ISR missions and the Airbus approach of combining an invariant feature extraction using pre-trained CNNs and the high-speed training and classification ability of a novel frequency-domain SVM training method. The frequency-domain approach allows for a highly optimized implementation for General Purpose Computation on a Graphics Processing Unit (GPGPU) and also an efficient training of large training samples. The selected CNN which is pre-trained only once on domain-extrinsic data reveals a highly invariant feature extraction. This allows for a significantly reduced adaptation and training of the target recognition method for new target classes and mission scenarios. A comprehensive training and test dataset was defined and prepared using relevant high-definition airborne video sequences. The assessment concept is explained and performance results are given using the established precision-recall diagrams, average precision and runtime figures on representative test data. A comparison to legacy target recognition approaches shows the impressive performance increase by the proposed CNN+SVM machine-learning approach and the capability of real-time high

  18. 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.

  19. Decoding the patterns of ubiquitin recognition by ubiquitin-associated domains from free energy simulations.

    PubMed

    Bouvier, Benjamin

    2014-01-07

    Ubiquitin is a highly conserved, highly represented protein acting as a regulating signal in numerous cellular processes. It leverages a single hydrophobic binding patch to recognize and bind a large variety of protein domains with remarkable specificity, but can also self-assemble into chains of poly-diubiquitin units in which these interfaces are sequestered, profoundly altering the individual monomers' recognition characteristics. Despite numerous studies, the origins of this varied specificity and the competition between substrates for the binding of the ubiquitin interface patch remain under heated debate. This study uses enhanced sampling all-atom molecular dynamics to simulate the unbinding of complexes of mono- or K48-linked diubiquitin bound to several ubiquitin-associated domains, providing insights into the mechanism and free energetics of ubiquitin recognition and binding. The implications for the subtle tradeoff between the stability of the polyubiquitin signal and its easy recognition by target protein assemblies are discussed, as is the enhanced affinity of the latter for long polyubiquitin chains compared to isolated mono- or diubiquitin.

  20. Domain Regeneration for Cross-Database Micro-Expression Recognition

    NASA Astrophysics Data System (ADS)

    Zong, Yuan; Zheng, Wenming; Huang, Xiaohua; Shi, Jingang; Cui, Zhen; Zhao, Guoying

    2018-05-01

    In this paper, we investigate the cross-database micro-expression recognition problem, where the training and testing samples are from two different micro-expression databases. Under this setting, the training and testing samples would have different feature distributions and hence the performance of most existing micro-expression recognition methods may decrease greatly. To solve this problem, we propose a simple yet effective method called Target Sample Re-Generator (TSRG) in this paper. By using TSRG, we are able to re-generate the samples from target micro-expression database and the re-generated target samples would share same or similar feature distributions with the original source samples. For this reason, we can then use the classifier learned based on the labeled source samples to accurately predict the micro-expression categories of the unlabeled target samples. To evaluate the performance of the proposed TSRG method, extensive cross-database micro-expression recognition experiments designed based on SMIC and CASME II databases are conducted. Compared with recent state-of-the-art cross-database emotion recognition methods, the proposed TSRG achieves more promising results.

  1. Adaptive optics to enhance target recognition

    NASA Astrophysics Data System (ADS)

    McAulay, Alastair D.

    2012-06-01

    Target recognition can be enhanced by reducing image degradation due to atmospheric turbulence. This is accomplished by an adaptive optic system. We discuss the forms of degradation when a target is viewed through the atmosphere1: scintillation from ground targets on a hot day in visible or infrared light; beam spreading and wavering around in time; atmospheric turbulence caused by motion of the target or by weather. In the case of targets we can use a beacon laser that reflects back from the target into a wavefront detector to measure the effects of turbulence on propagation to and from the target before imaging.1 A deformable mirror then corrects the wavefront shape of the transmitted, reflected or scattered data for enhanced imaging. Further, recognition of targets is enhanced by performing accurate distance measurements to localized parts of the target using lidar. Distance is obtained by sending a short pulse to the target and measuring the time for the pulse to return. There is inadequate time to scan the complete field of view so that the beam must be steered to regions of interest such as extremities of the image during image recognition. Distance is particularly valuable to recognize fine features in range along the target or when segmentation is required to separate a target from background or from other targets. We discuss the issues involved.

  2. The research of multi-frame target recognition based on laser active imaging

    NASA Astrophysics Data System (ADS)

    Wang, Can-jin; Sun, Tao; Wang, Tin-feng; Chen, Juan

    2013-09-01

    Laser active imaging is fit to conditions such as no difference in temperature between target and background, pitch-black night, bad visibility. Also it can be used to detect a faint target in long range or small target in deep space, which has advantage of high definition and good contrast. In one word, it is immune to environment. However, due to the affect of long distance, limited laser energy and atmospheric backscatter, it is impossible to illuminate the whole scene at the same time. It means that the target in every single frame is unevenly or partly illuminated, which make the recognition more difficult. At the same time the speckle noise which is common in laser active imaging blurs the images . In this paper we do some research on laser active imaging and propose a new target recognition method based on multi-frame images . Firstly, multi pulses of laser is used to obtain sub-images for different parts of scene. A denoising method combined homomorphic filter with wavelet domain SURE is used to suppress speckle noise. And blind deconvolution is introduced to obtain low-noise and clear sub-images. Then these sub-images are registered and stitched to combine a completely and uniformly illuminated scene image. After that, a new target recognition method based on contour moments is proposed. Firstly, canny operator is used to obtain contours. For each contour, seven invariant Hu moments are calculated to generate the feature vectors. At last the feature vectors are input into double hidden layers BP neural network for classification . Experiments results indicate that the proposed algorithm could achieve a high recognition rate and satisfactory real-time performance for laser active imaging.

  3. Cross domains Arabic named entity recognition system

    NASA Astrophysics Data System (ADS)

    Al-Ahmari, S. Saad; Abdullatif Al-Johar, B.

    2016-07-01

    Named Entity Recognition (NER) plays an important role in many Natural Language Processing (NLP) applications such as; Information Extraction (IE), Question Answering (QA), Text Clustering, Text Summarization and Word Sense Disambiguation. This paper presents the development and implementation of domain independent system to recognize three types of Arabic named entities. The system works based on a set of domain independent grammar-rules along with Arabic part of speech tagger in addition to gazetteers and lists of trigger words. The experimental results shown, that the system performed as good as other systems with better results in some cases of cross-domains corpora.

  4. Elucidation of the binding preferences of peptide recognition modules: SH3 and PDZ domains.

    PubMed

    Teyra, Joan; Sidhu, Sachdev S; Kim, Philip M

    2012-08-14

    Peptide-binding domains play a critical role in regulation of cellular processes by mediating protein interactions involved in signalling. In recent years, the development of large-scale technologies has enabled exhaustive studies on the peptide recognition preferences for a number of peptide-binding domain families. These efforts have provided significant insights into the binding specificities of these modular domains. Many research groups have taken advantage of this unprecedented volume of specificity data and have developed a variety of new algorithms for the prediction of binding specificities of peptide-binding domains and for the prediction of their natural binding targets. This knowledge has also been applied to the design of synthetic peptide-binding domains in order to rewire protein-protein interaction networks. Here, we describe how these experimental technologies have impacted on our understanding of peptide-binding domain specificities and on the elucidation of their natural ligands. We discuss SH3 and PDZ domains as well characterized examples, and we explore the feasibility of expanding high-throughput experiments to other peptide-binding domains. Copyright © 2012. Published by Elsevier B.V.

  5. A novel paired domain DNA recognition motif can mediate Pax2 repression of gene transcription.

    PubMed

    Håvik, B; Ragnhildstveit, E; Lorens, J B; Saelemyr, K; Fauske, O; Knudsen, L K; Fjose, A

    1999-12-20

    The paired domain (PD) is an evolutionarily conserved DNA-binding domain encoded by the Pax gene family of developmental regulators. The Pax proteins are transcription factors and are involved in a variety of processes such as brain development, patterning of the central nervous system (CNS), and B-cell development. In this report we demonstrate that the zebrafish Pax2 PD can interact with a novel type of DNA sequences in vitro, the triple-A motif, consisting of a heptameric nucleotide sequence G/CAAACA/TC with an invariant core of three adjacent adenosines. This recognition sequence was found to be conserved in known natural Pax5 repressor elements involved in controlling the expression of the p53 and J-chain genes. By identifying similar high affinity binding sites in potential target genes of the Pax2 protein, including the pax2 gene itself, we obtained further evidence that the triple-A sites are biologically significant. The putative natural target sites also provide a basis for defining an extended consensus recognition sequence. In addition, we observed in transformation assays a direct correlation between Pax2 repressor activity and the presence of triple-A sites. The results suggest that a transcriptional regulatory function of Pax proteins can be modulated by PD binding to different categories of target sequences. Copyright 1999 Academic Press.

  6. Public domain optical character recognition

    NASA Astrophysics Data System (ADS)

    Garris, Michael D.; Blue, James L.; Candela, Gerald T.; Dimmick, Darrin L.; Geist, Jon C.; Grother, Patrick J.; Janet, Stanley A.; Wilson, Charles L.

    1995-03-01

    A public domain document processing system has been developed by the National Institute of Standards and Technology (NIST). The system is a standard reference form-based handprint recognition system for evaluating optical character recognition (OCR), and it is intended to provide a baseline of performance on an open application. The system's source code, training data, performance assessment tools, and type of forms processed are all publicly available. The system recognizes the handprint entered on handwriting sample forms like the ones distributed with NIST Special Database 1. From these forms, the system reads hand-printed numeric fields, upper and lowercase alphabetic fields, and unconstrained text paragraphs comprised of words from a limited-size dictionary. The modular design of the system makes it useful for component evaluation and comparison, training and testing set validation, and multiple system voting schemes. The system contains a number of significant contributions to OCR technology, including an optimized probabilistic neural network (PNN) classifier that operates a factor of 20 times faster than traditional software implementations of the algorithm. The source code for the recognition system is written in C and is organized into 11 libraries. In all, there are approximately 19,000 lines of code supporting more than 550 subroutines. Source code is provided for form registration, form removal, field isolation, field segmentation, character normalization, feature extraction, character classification, and dictionary-based postprocessing. The recognition system has been successfully compiled and tested on a host of UNIX workstations. This paper gives an overview of the recognition system's software architecture, including descriptions of the various system components along with timing and accuracy statistics.

  7. Mechanism of intermediate filament recognition by plakin repeat domains revealed by envoplakin targeting of vimentin

    NASA Astrophysics Data System (ADS)

    Fogl, Claudia; Mohammed, Fiyaz; Al-Jassar, Caezar; Jeeves, Mark; Knowles, Timothy J.; Rodriguez-Zamora, Penelope; White, Scott A.; Odintsova, Elena; Overduin, Michael; Chidgey, Martyn

    2016-03-01

    Plakin proteins form critical connections between cell junctions and the cytoskeleton; their disruption within epithelial and cardiac muscle cells cause skin-blistering diseases and cardiomyopathies. Envoplakin has a single plakin repeat domain (PRD) which recognizes intermediate filaments through an unresolved mechanism. Herein we report the crystal structure of envoplakin's complete PRD fold, revealing binding determinants within its electropositive binding groove. Four of its five internal repeats recognize negatively charged patches within vimentin via five basic determinants that are identified by nuclear magnetic resonance spectroscopy. Mutations of the Lys1901 or Arg1914 binding determinants delocalize heterodimeric envoplakin from intracellular vimentin and keratin filaments in cultured cells. Recognition of vimentin is abolished when its residues Asp112 or Asp119 are mutated. The latter slot intermediate filament rods into basic PRD domain grooves through electrosteric complementarity in a widely applicable mechanism. Together this reveals how plakin family members form dynamic linkages with cytoskeletal frameworks.

  8. Unification of automatic target tracking and automatic target recognition

    NASA Astrophysics Data System (ADS)

    Schachter, Bruce J.

    2014-06-01

    The subject being addressed is how an automatic target tracker (ATT) and an automatic target recognizer (ATR) can be fused together so tightly and so well that their distinctiveness becomes lost in the merger. This has historically not been the case outside of biology and a few academic papers. The biological model of ATT∪ATR arises from dynamic patterns of activity distributed across many neural circuits and structures (including retina). The information that the brain receives from the eyes is "old news" at the time that it receives it. The eyes and brain forecast a tracked object's future position, rather than relying on received retinal position. Anticipation of the next moment - building up a consistent perception - is accomplished under difficult conditions: motion (eyes, head, body, scene background, target) and processing limitations (neural noise, delays, eye jitter, distractions). Not only does the human vision system surmount these problems, but it has innate mechanisms to exploit motion in support of target detection and classification. Biological vision doesn't normally operate on snapshots. Feature extraction, detection and recognition are spatiotemporal. When vision is viewed as a spatiotemporal process, target detection, recognition, tracking, event detection and activity recognition, do not seem as distinct as they are in current ATT and ATR designs. They appear as similar mechanism taking place at varying time scales. A framework is provided for unifying ATT and ATR.

  9. Metal cofactor modulated folding and target recognition of HIV-1 NCp7.

    PubMed

    Ren, Weitong; Ji, Dongqing; Xu, Xiulian

    2018-01-01

    The HIV-1 nucleocapsid 7 (NCp7) plays crucial roles in multiple stages of HIV-1 life cycle, and its biological functions rely on the binding of zinc ions. Understanding the molecular mechanism of how the zinc ions modulate the conformational dynamics and functions of the NCp7 is essential for the drug development and HIV-1 treatment. In this work, using a structure-based coarse-grained model, we studied the effects of zinc cofactors on the folding and target RNA(SL3) recognition of the NCp7 by molecular dynamics simulations. After reproducing some key properties of the zinc binding and folding of the NCp7 observed in previous experiments, our simulations revealed several interesting features in the metal ion modulated folding and target recognition. Firstly, we showed that the zinc binding makes the folding transition states of the two zinc fingers less structured, which is in line with the Hammond effect observed typically in mutation, temperature or denaturant induced perturbations to protein structure and stability. Secondly, We showed that there exists mutual interplay between the zinc ion binding and NCp7-target recognition. Binding of zinc ions enhances the affinity between the NCp7 and the target RNA, whereas the formation of the NCp7-RNA complex reshapes the intrinsic energy landscape of the NCp7 and increases the stability and zinc affinity of the two zinc fingers. Thirdly, by characterizing the effects of salt concentrations on the target RNA recognition, we showed that the NCp7 achieves optimal balance between the affinity and binding kinetics near the physiologically relevant salt concentrations. In addition, the effects of zinc binding on the inter-domain conformational flexibility and folding cooperativity of the NCp7 were also discussed.

  10. Deep kernel learning method for SAR image target recognition

    NASA Astrophysics Data System (ADS)

    Chen, Xiuyuan; Peng, Xiyuan; Duan, Ran; Li, Junbao

    2017-10-01

    With the development of deep learning, research on image target recognition has made great progress in recent years. Remote sensing detection urgently requires target recognition for military, geographic, and other scientific research. This paper aims to solve the synthetic aperture radar image target recognition problem by combining deep and kernel learning. The model, which has a multilayer multiple kernel structure, is optimized layer by layer with the parameters of Support Vector Machine and a gradient descent algorithm. This new deep kernel learning method improves accuracy and achieves competitive recognition results compared with other learning methods.

  11. Directing an artificial zinc finger protein to new targets by fusion to a non-DNA-binding domain.

    PubMed

    Lim, Wooi F; Burdach, Jon; Funnell, Alister P W; Pearson, Richard C M; Quinlan, Kate G R; Crossley, Merlin

    2016-04-20

    Transcription factors are often regarded as having two separable components: a DNA-binding domain (DBD) and a functional domain (FD), with the DBD thought to determine target gene recognition. While this holds true for DNA bindingin vitro, it appears thatin vivoFDs can also influence genomic targeting. We fused the FD from the well-characterized transcription factor Krüppel-like Factor 3 (KLF3) to an artificial zinc finger (AZF) protein originally designed to target the Vascular Endothelial Growth Factor-A (VEGF-A) gene promoter. We compared genome-wide occupancy of the KLF3FD-AZF fusion to that observed with AZF. AZF bound to theVEGF-Apromoter as predicted, but was also found to occupy approximately 25,000 other sites, a large number of which contained the expected AZF recognition sequence, GCTGGGGGC. Interestingly, addition of the KLF3 FD re-distributes the fusion protein to new sites, with total DNA occupancy detected at around 50,000 sites. A portion of these sites correspond to known KLF3-bound regions, while others contained sequences similar but not identical to the expected AZF recognition sequence. These results show that FDs can influence and may be useful in directing AZF DNA-binding proteins to specific targets and provide insights into how natural transcription factors operate. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  12. Active Multimodal Sensor System for Target Recognition and Tracking

    PubMed Central

    Zhang, Guirong; Zou, Zhaofan; Liu, Ziyue; Mao, Jiansen

    2017-01-01

    High accuracy target recognition and tracking systems using a single sensor or a passive multisensor set are susceptible to external interferences and exhibit environmental dependencies. These difficulties stem mainly from limitations to the available imaging frequency bands, and a general lack of coherent diversity of the available target-related data. This paper proposes an active multimodal sensor system for target recognition and tracking, consisting of a visible, an infrared, and a hyperspectral sensor. The system makes full use of its multisensor information collection abilities; furthermore, it can actively control different sensors to collect additional data, according to the needs of the real-time target recognition and tracking processes. This level of integration between hardware collection control and data processing is experimentally shown to effectively improve the accuracy and robustness of the target recognition and tracking system. PMID:28657609

  13. Fast cat-eye effect target recognition based on saliency extraction

    NASA Astrophysics Data System (ADS)

    Li, Li; Ren, Jianlin; Wang, Xingbin

    2015-09-01

    Background complexity is a main reason that results in false detection in cat-eye target recognition. Human vision has selective attention property which can help search the salient target from complex unknown scenes quickly and precisely. In the paper, we propose a novel cat-eye effect target recognition method named Multi-channel Saliency Processing before Fusion (MSPF). This method combines traditional cat-eye target recognition with the selective characters of visual attention. Furthermore, parallel processing enables it to achieve fast recognition. Experimental results show that the proposed method performs better in accuracy, robustness and speed compared to other methods.

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

    NASA Astrophysics Data System (ADS)

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

    2016-08-01

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

  15. A universal entropy-driven mechanism for thioredoxin–target recognition

    PubMed Central

    Palde, Prakash B.; Carroll, Kate S.

    2015-01-01

    Cysteine residues in cytosolic proteins are maintained in their reduced state, but can undergo oxidation owing to posttranslational modification during redox signaling or under conditions of oxidative stress. In large part, the reduction of oxidized protein cysteines is mediated by a small 12-kDa thiol oxidoreductase, thioredoxin (Trx). Trx provides reducing equivalents for central metabolic enzymes and is implicated in redox regulation of a wide number of target proteins, including transcription factors. Despite its importance in cellular redox homeostasis, the precise mechanism by which Trx recognizes target proteins, especially in the absence of any apparent signature binding sequence or motif, remains unknown. Knowledge of the forces associated with the molecular recognition that governs Trx–protein interactions is fundamental to our understanding of target specificity. To gain insight into Trx–target recognition, we have thermodynamically characterized the noncovalent interactions between Trx and target proteins before S-S reduction using isothermal titration calorimetry (ITC). Our findings indicate that Trx recognizes the oxidized form of its target proteins with exquisite selectivity, compared with their reduced counterparts. Furthermore, we show that recognition is dependent on the conformational restriction inherent to oxidized targets. Significantly, the thermodynamic signatures for multiple Trx targets reveal favorable entropic contributions as the major recognition force dictating these protein–protein interactions. Taken together, our data afford significant new insight into the molecular forces responsible for Trx–target recognition and should aid the design of new strategies for thiol oxidoreductase inhibition. PMID:26080424

  16. Non-Cooperative Target Recognition by Means of Singular Value Decomposition Applied to Radar High Resolution Range Profiles †

    PubMed Central

    López-Rodríguez, Patricia; Escot-Bocanegra, David; Fernández-Recio, Raúl; Bravo, Ignacio

    2015-01-01

    Radar high resolution range profiles are widely used among the target recognition community for the detection and identification of flying targets. In this paper, singular value decomposition is applied to extract the relevant information and to model each aircraft as a subspace. The identification algorithm is based on angle between subspaces and takes place in a transformed domain. In order to have a wide database of radar signatures and evaluate the performance, simulated range profiles are used as the recognition database while the test samples comprise data of actual range profiles collected in a measurement campaign. Thanks to the modeling of aircraft as subspaces only the valuable information of each target is used in the recognition process. Thus, one of the main advantages of using singular value decomposition, is that it helps to overcome the notable dissimilarities found in the shape and signal-to-noise ratio between actual and simulated profiles due to their difference in nature. Despite these differences, the recognition rates obtained with the algorithm are quite promising. PMID:25551484

  17. 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.

  18. Fine tuning cellular recognition: The function of the leucine rich repeat (LRR) trans-membrane protein, LRT, in muscle targeting to tendon cells.

    PubMed

    Gilsohn, Eli; Volk, Talila

    2010-01-01

    The formation of complex tissues during embryonic development is often accompanied by directed cellular migration towards a target tissue. Specific mutual recognition between the migrating cell and its target tissue leads to the arrest of the cell migratory behavior and subsequent contact formation between the two interacting cell types. Recent studies implicated a novel family of surface proteins containing a trans-membrane domain and single leucine-rich repeat (LRR) domain in inter-cellular recognition and the arrest of cell migration. Here, we describe the involvement of a novel LRR surface protein, LRT, in targeting migrating muscles towards their corresponding tendon cells in the Drosophila embryo. LRT is specifically expressed by the target tendon cells and is essential for arresting the migratory behavior of the muscle cells. Additional studies in Drosophila S2 cultured cells suggest that LRT forms a protein complex with the Roundabout (Robo) receptor, essential for guiding muscles towards their tendon partners. Genetic analysis supports a model in which LRT performs its activity non-autonomously through its interaction with the Robo receptors expressed on the muscle surfaces. These results suggest a novel mechanism of intercellular recognition through interactions between LRR family members and Robo receptors.

  19. Shape and texture fused recognition of flying targets

    NASA Astrophysics Data System (ADS)

    Kovács, Levente; Utasi, Ákos; Kovács, Andrea; Szirányi, Tamás

    2011-06-01

    This paper presents visual detection and recognition of flying targets (e.g. planes, missiles) based on automatically extracted shape and object texture information, for application areas like alerting, recognition and tracking. Targets are extracted based on robust background modeling and a novel contour extraction approach, and object recognition is done by comparisons to shape and texture based query results on a previously gathered real life object dataset. Application areas involve passive defense scenarios, including automatic object detection and tracking with cheap commodity hardware components (CPU, camera and GPS).

  20. Target recognition of beta2-glycoprotein I (beta2GPI)-dependent anticardiolipin antibodies: evidence for involvement of the fourth domain of beta2GPI in antibody binding.

    PubMed

    George, J; Gilburd, B; Hojnik, M; Levy, Y; Langevitz, P; Matsuura, E; Koike, T; Shoenfeld, Y

    1998-04-15

    Beta2-glycoprotein I (beta2GPI) is an absolute requirement for the binding of autoimmune anticardiolipin Abs (aCL) to cardiolipin (CL). We evaluated the target recognition of human beta2GPI by IgG derived from two patients with primary and two with secondary antiphospholipid syndrome. The total IgG serum fractions and beta2GPI affinity-purified IgGs were assessed by using various domain-deleted mutants (DM) of human beta2GPI (DMs: I-III, I-IV, II-V, III-V, IV-V, and V) and mouse mAbs against individual beta2GPI domains. The four IgGs bound slightly to CL in the absence of beta2GPI and showed increased binding in the beta2GPI presence. Following affinity purification of the IgGs on a beta2GPI column, reactivity toward CL was absent. DMs containing domain V inhibited the binding of biotinylated beta2GPI to CL. The addition to CL-coated plates of DM V, but not the other DMs, reduced the binding of all four IgGs. The anti-beta2GPI IgGs bound only to complete beta2GPI and DM I-IV coated on the plates. The binding to plate-adsorbed beta2GPI could be inhibited by complete beta2GPI and DM I-IV, the latter being a more efficient inhibitor. Further, the human anti-beta2GPI IgGs could compete with the binding to beta2GPI of Cof-21 mouse mAb (directed at domain IV), but not with the two other mouse mAbs. The results suggest that some "autoimmune:" beta2GPI-dependent anticardiolipin Abs recognize a beta2GPI target that is distinct from the CL-binding site in domain V. The target site for some antiphospholipid syndrome IgGs appear to reside in domain IV of beta2GPI.

  1. Component-based target recognition inspired by human vision

    NASA Astrophysics Data System (ADS)

    Zheng, Yufeng; Agyepong, Kwabena

    2009-05-01

    In contrast with machine vision, human can recognize an object from complex background with great flexibility. For example, given the task of finding and circling all cars (no further information) in a picture, you may build a virtual image in mind from the task (or target) description before looking at the picture. Specifically, the virtual car image may be composed of the key components such as driver cabin and wheels. In this paper, we propose a component-based target recognition method by simulating the human recognition process. The component templates (equivalent to the virtual image in mind) of the target (car) are manually decomposed from the target feature image. Meanwhile, the edges of the testing image can be extracted by using a difference of Gaussian (DOG) model that simulates the spatiotemporal response in visual process. A phase correlation matching algorithm is then applied to match the templates with the testing edge image. If all key component templates are matched with the examining object, then this object is recognized as the target. Besides the recognition accuracy, we will also investigate if this method works with part targets (half cars). In our experiments, several natural pictures taken on streets were used to test the proposed method. The preliminary results show that the component-based recognition method is very promising.

  2. Logo recognition using alpha-rooted phase correlation in the radon transform domain

    NASA Astrophysics Data System (ADS)

    DelMarco, Stephen

    2009-08-01

    Alpha-rooted phase correlation (ARPC) is a recently-developed variant of classical phase correlation that includes a Fourier domain image enhancement operation. ARPC combines classical phase correlation with alpha-rooting to provide tunable image enhancement. The alpha-rooting parameters may be adjusted to provide a tradeoff between height and width of the ARPC main lobe. A high narrow main lobe peak provides high matching accuracy for aligned images, but reduced matching performance for misaligned logos. A lower, wider peak trades matching accuracy on aligned logos, for improved matching performance on misaligned imagery. Previously, we developed ARPC and used it in the spatial domain for logo recognition as part of an overall automated document analysis problem. However, spatial domain ARPC performance can be sensitive to logo misalignments, including rotational misalignment. In this paper we use ARPC as a match metric in the radon transform domain for logo recognition. In the radon transform domain, rotational misalignments correspond to translations in the radon transform angle parameter. These translations are captured by ARPC, thereby producing rotation-invariant logo matching. In the paper, we first present an overview of ARPC, and then describe the logo matching algorithm. We present numerical performance results demonstrating matching tolerance to rotational misalignments. We demonstrate robustness of the radon transform domain rotation estimation to noise. We present logo verification and recognition performance results using the proposed approach on a public domain logo database. We compare performance results to performance obtained using spatial domain ARPC, and state-of-the-art SURF features, for logos in salt-and-pepper noise.

  3. Exploring the functional architecture of person recognition system with event-related potentials in a within- and cross-domain self-priming of faces.

    PubMed

    Jemel, Boutheina; Pisani, Michèle; Rousselle, Laurence; Crommelinck, Marc; Bruyer, Raymond

    2005-01-01

    In this paper, we explored the functional properties of person recognition system by investigating the onset, magnitude, and scalp distribution of within- and cross-domain self-priming effects on event-related potentials (ERPs). Recognition of degraded pictures of famous people was enhanced by a prior exposure to the same person's face (within-domain self-priming) or name (cross-domain self-priming) as compared to those preceded by neutral or unrelated primes. The ERP results showed first that the amplitude of the N170 component to famous face targets was modulated by within- and cross-domain self-priming, suggesting not only that the N170 component can be affected by top-down influences but also that this top-down effect crosses domains. Second, similar to our behavioral data, later ERPs to famous faces showed larger ERP self-priming effects in the within-domain than in the cross-domain condition. In addition, the present data dissociated between two topographically and temporally overlapping priming-sensitive ERP components: the first one, with a strongly posterior distribution arising at an early onset, was modulated more by within-domain priming irrespective whether the repeated face was familiar or not. The second component, with a relatively uniform scalp distribution, was modulated by within- and cross-domain priming of familiar faces. Moreover, there was no evidence for ERP-induced modulations for unfamiliar face targets in the cross-domain condition. Together, our findings suggest that multiple neurocognitive events that are possibly mediated by distinct brain loci contribute to face priming effects.

  4. Extracting sets of chemical substructures and protein domains governing drug-target interactions.

    PubMed

    Yamanishi, Yoshihiro; Pauwels, Edouard; Saigo, Hiroto; Stoven, Véronique

    2011-05-23

    The identification of rules governing molecular recognition between drug chemical substructures and protein functional sites is a challenging issue at many stages of the drug development process. In this paper we develop a novel method to extract sets of drug chemical substructures and protein domains that govern drug-target interactions on a genome-wide scale. This is made possible using sparse canonical correspondence analysis (SCCA) for analyzing drug substructure profiles and protein domain profiles simultaneously. The method does not depend on the availability of protein 3D structures. From a data set of known drug-target interactions including enzymes, ion channels, G protein-coupled receptors, and nuclear receptors, we extract a set of chemical substructures shared by drugs able to bind to a set of protein domains. These two sets of extracted chemical substructures and protein domains form components that can be further exploited in a drug discovery process. This approach successfully clusters protein domains that may be evolutionary unrelated but that bind a common set of chemical substructures. As shown in several examples, it can also be very helpful for predicting new protein-ligand interactions and addressing the problem of ligand specificity. The proposed method constitutes a contribution to the recent field of chemogenomics that aims to connect the chemical space with the biological space.

  5. Automated target recognition and tracking using an optical pattern recognition neural network

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin

    1991-01-01

    The on-going development of an automatic target recognition and tracking system at the Jet Propulsion Laboratory is presented. This system is an optical pattern recognition neural network (OPRNN) that is an integration of an innovative optical parallel processor and a feature extraction based neural net training algorithm. The parallel optical processor provides high speed and vast parallelism as well as full shift invariance. The neural network algorithm enables simultaneous discrimination of multiple noisy targets in spite of their scales, rotations, perspectives, and various deformations. This fully developed OPRNN system can be effectively utilized for the automated spacecraft recognition and tracking that will lead to success in the Automated Rendezvous and Capture (AR&C) of the unmanned Cargo Transfer Vehicle (CTV). One of the most powerful optical parallel processors for automatic target recognition is the multichannel correlator. With the inherent advantages of parallel processing capability and shift invariance, multiple objects can be simultaneously recognized and tracked using this multichannel correlator. This target tracking capability can be greatly enhanced by utilizing a powerful feature extraction based neural network training algorithm such as the neocognitron. The OPRNN, currently under investigation at JPL, is constructed with an optical multichannel correlator where holographic filters have been prepared using the neocognitron training algorithm. The computation speed of the neocognitron-type OPRNN is up to 10(exp 14) analog connections/sec that enabling the OPRNN to outperform its state-of-the-art electronics counterpart by at least two orders of magnitude.

  6. Structural insight into the role of VAL1 B3 domain for targeting to FLC locus in Arabidopsis thaliana.

    PubMed

    Wu, Baixing; Zhang, Mengmeng; Su, Shichen; Liu, Hehua; Gan, Jianhua; Ma, Jinbiao

    2018-06-22

    Vernalization is a pivotal stage for some plants involving many epigenetic changes during cold exposure. In Arabidopsis, an essential step in vernalization for further flowering is successful silence the potent floral repressor Flowering Locus C (FLC) by repressing histone mark. AtVal1 is a multi-function protein containing five domains that participate into many recognition processes and is validated to recruit the repress histone modifier PHD-PRC2 complex and interact with components of the ASAP complex target to the FLC nucleation region through recognizing a cis element known as CME (cold memory element) by its plant-specific B3 domain. Here, we determine the crystal structure of the B3 domain in complex with Sph/RY motif in CME. Our structural analysis reveals the specific DNA recognition by B3 domain, combined with our in vitro experiments, we provide the structural insight into the important implication of AtVAL1-B3 domain in flowering process. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. [A new mechanism of ubiquitin-dependent proteolytic pathway--polyubiquitin chain recognition and proteasomal targeting].

    PubMed

    Kawahara, Hiroyuki; Yokosawa, Hideyoshi

    2008-01-01

    The RPN10 subunit of 26S proteasome and several UBA domain proteins can bind to the polyubiquitin chain and play a role as ubiquitin receptors of the 26S proteasome. Although it was thought that substrate recognition is an essential step in the proteasome-mediated protein degradation, deletion of rpn10 genes in yeast does not influence the viability of cells but instead causes only a mild phenotype, suggesting that the above ubiquitin receptors are redundantly involved in substrate delivery to the proteasome. However, their functional difference is still enigmatic. In this review, we summarize recent advances in polyubiquitin chain recognition/delivery system and provide potential applications to modulate this system as a probable target for drug development.

  8. Composite Wavelet Filters for Enhanced Automated Target Recognition

    NASA Technical Reports Server (NTRS)

    Chiang, Jeffrey N.; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

    2012-01-01

    Automated Target Recognition (ATR) systems aim to automate target detection, recognition, and tracking. The current project applies a JPL ATR system to low-resolution sonar and camera videos taken from unmanned vehicles. These sonar images are inherently noisy and difficult to interpret, and pictures taken underwater are unreliable due to murkiness and inconsistent lighting. The ATR system breaks target recognition into three stages: 1) Videos of both sonar and camera footage are broken into frames and preprocessed to enhance images and detect Regions of Interest (ROIs). 2) Features are extracted from these ROIs in preparation for classification. 3) ROIs are classified as true or false positives using a standard Neural Network based on the extracted features. Several preprocessing, feature extraction, and training methods are tested and discussed in this paper.

  9. Detection and recognition of targets by using signal polarization properties

    NASA Astrophysics Data System (ADS)

    Ponomaryov, Volodymyr I.; Peralta-Fabi, Ricardo; Popov, Anatoly V.; Babakov, Mikhail F.

    1999-08-01

    The quality of radar target recognition can be enhanced by exploiting its polarization signatures. A specialized X-band polarimetric radar was used for target recognition in experimental investigations. The following polarization characteristics connected to the object geometrical properties were investigated: the amplitudes of the polarization matrix elements; an anisotropy coefficient; depolarization coefficient; asymmetry coefficient; the energy of a backscattering signal; object shape factor. A large quantity of polarimetric radar data was measured and processed to form a database of different object and different weather conditions. The histograms of polarization signatures were approximated by a Nakagami distribution, then used for real- time target recognition. The Neyman-Pearson criterion was used for the target detection, and the criterion of the maximum of a posterior probability was used for recognition problem. Some results of experimental verification of pattern recognition and detection of objects with different electrophysical and geometrical characteristics urban in clutter are presented in this paper.

  10. Assembly and analysis of eukaryotic Argonaute–RNA complexes in microRNA-target recognition

    PubMed Central

    Gan, Hin Hark; Gunsalus, Kristin C.

    2015-01-01

    Experimental studies have uncovered a variety of microRNA (miRNA)–target duplex structures that include perfect, imperfect and seedless duplexes. However, non-canonical binding modes from imperfect/seedless duplexes are not well predicted by computational approaches, which rely primarily on sequence and secondary structural features, nor have their tertiary structures been characterized because solved structures to date are limited to near perfect, straight duplexes in Argonautes (Agos). Here, we use structural modeling to examine the role of Ago dynamics in assembling viable eukaryotic miRNA-induced silencing complexes (miRISCs). We show that combinations of low-frequency, global modes of motion of Ago domains are required to accommodate RNA duplexes in model human and C. elegans Ago structures. Models of viable miRISCs imply that Ago adopts variable conformations at distinct target sites that generate distorted, imperfect miRNA-target duplexes. Ago's ability to accommodate a duplex is dependent on the region where structural distortions occur: distortions in solvent-exposed seed and 3′-end regions are less likely to produce steric clashes than those in the central duplex region. Energetic analyses of assembled miRISCs indicate that target recognition is also driven by favorable Ago-duplex interactions. Such structural insights into Ago loading and target recognition mechanisms may provide a more accurate assessment of miRNA function. PMID:26432829

  11. Structural analysis of poly-SUMO chain recognition by the RNF4-SIMs domain.

    PubMed

    Kung, Camy C-H; Naik, Mandar T; Wang, Szu-Huan; Shih, Hsiu-Ming; Chang, Che-Chang; Lin, Li-Ying; Chen, Chia-Lin; Ma, Che; Chang, Chi-Fon; Huang, Tai-Huang

    2014-08-15

    The E3 ubiquitin ligase RNF4 (RING finger protein 4) contains four tandem SIM [SUMO (small ubiquitin-like modifier)-interaction motif] repeats for selective interaction with poly-SUMO-modified proteins, which it targets for degradation. We employed a multi-faceted approach to characterize the structure of the RNF4-SIMs domain and the tetra-SUMO2 chain to elucidate the interaction between them. In solution, the SIM domain was intrinsically disordered and the linkers of the tetra-SUMO2 were highly flexible. Individual SIMs of the RNF4-SIMs domains bind to SUMO2 in the groove between the β2-strand and the α1-helix parallel to the β2-strand. SIM2 and SIM3 bound to SUMO with a high affinity and together constituted the recognition module necessary for SUMO binding. SIM4 alone bound to SUMO with low affinity; however, its contribution to tetra-SUMO2 binding avidity is comparable with that of SIM3 when in the RNF4-SIMs domain. The SAXS data of the tetra-SUMO2-RNF4-SIMs domain complex indicate that it exists as an ordered structure. The HADDOCK model showed that the tandem RNF4-SIMs domain bound antiparallel to the tetra-SUMO2 chain orientation and wrapped around the SUMO protamers in a superhelical turn without imposing steric hindrance on either molecule.

  12. Extended target recognition in cognitive radar networks.

    PubMed

    Wei, Yimin; Meng, Huadong; Liu, Yimin; Wang, Xiqin

    2010-01-01

    We address the problem of adaptive waveform design for extended target recognition in cognitive radar networks. A closed-loop active target recognition radar system is extended to the case of a centralized cognitive radar network, in which a generalized likelihood ratio (GLR) based sequential hypothesis testing (SHT) framework is employed. Using Doppler velocities measured by multiple radars, the target aspect angle for each radar is calculated. The joint probability of each target hypothesis is then updated using observations from different radar line of sights (LOS). Based on these probabilities, a minimum correlation algorithm is proposed to adaptively design the transmit waveform for each radar in an amplitude fluctuation situation. Simulation results demonstrate performance improvements due to the cognitive radar network and adaptive waveform design. Our minimum correlation algorithm outperforms the eigen-waveform solution and other non-cognitive waveform design approaches.

  13. Target recognition based on convolutional neural network

    NASA Astrophysics Data System (ADS)

    Wang, Liqiang; Wang, Xin; Xi, Fubiao; Dong, Jian

    2017-11-01

    One of the important part of object target recognition is the feature extraction, which can be classified into feature extraction and automatic feature extraction. The traditional neural network is one of the automatic feature extraction methods, while it causes high possibility of over-fitting due to the global connection. The deep learning algorithm used in this paper is a hierarchical automatic feature extraction method, trained with the layer-by-layer convolutional neural network (CNN), which can extract the features from lower layers to higher layers. The features are more discriminative and it is beneficial to the object target recognition.

  14. Pornographic image recognition and filtering using incremental learning in compressed domain

    NASA Astrophysics Data System (ADS)

    Zhang, Jing; Wang, Chao; Zhuo, Li; Geng, Wenhao

    2015-11-01

    With the rapid development and popularity of the network, the openness, anonymity, and interactivity of networks have led to the spread and proliferation of pornographic images on the Internet, which have done great harm to adolescents' physical and mental health. With the establishment of image compression standards, pornographic images are mainly stored with compressed formats. Therefore, how to efficiently filter pornographic images is one of the challenging issues for information security. A pornographic image recognition and filtering method in the compressed domain is proposed by using incremental learning, which includes the following steps: (1) low-resolution (LR) images are first reconstructed from the compressed stream of pornographic images, (2) visual words are created from the LR image to represent the pornographic image, and (3) incremental learning is adopted to continuously adjust the classification rules to recognize the new pornographic image samples after the covering algorithm is utilized to train and recognize the visual words in order to build the initial classification model of pornographic images. The experimental results show that the proposed pornographic image recognition method using incremental learning has a higher recognition rate as well as costing less recognition time in the compressed domain.

  15. Laser range profiling for small target recognition

    NASA Astrophysics Data System (ADS)

    Steinvall, Ove; Tulldahl, Michael

    2016-05-01

    The detection and classification of small surface and airborne targets at long ranges is a growing need for naval security. Long range ID or ID at closer range of small targets has its limitations in imaging due to the demand on very high transverse sensor resolution. It is therefore motivated to look for 1D laser techniques for target ID. These include vibrometry, and laser range profiling. Vibrometry can give good results but is also sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angular resolved. The present paper will show both experimental and simulated results for laser range profiling of small boats out to 6-7 km range and a UAV mockup at close range (1.3 km). We obtained good results with the profiling system both for target detection and recognition. Comparison of experimental and simulated range waveforms based on CAD models of the target support the idea of having a profiling system as a first recognition sensor and thus narrowing the search space for the automatic target recognition based on imaging at close ranges. The naval experiments took place in the Baltic Sea with many other active and passive EO sensors beside the profiling system. Discussion of data fusion between laser profiling and imaging systems will be given. The UAV experiments were made from the rooftop laboratory at FOI.

  16. Evolutionary plasticity of the NHL domain underlies distinct solutions to RNA recognition.

    PubMed

    Kumari, Pooja; Aeschimann, Florian; Gaidatzis, Dimos; Keusch, Jeremy J; Ghosh, Pritha; Neagu, Anca; Pachulska-Wieczorek, Katarzyna; Bujnicki, Janusz M; Gut, Heinz; Großhans, Helge; Ciosk, Rafal

    2018-04-19

    RNA-binding proteins regulate all aspects of RNA metabolism. Their association with RNA is mediated by RNA-binding domains, of which many remain uncharacterized. A recently reported example is the NHL domain, found in prominent regulators of cellular plasticity like the C. elegans LIN-41. Here we employ an integrative approach to dissect the RNA specificity of LIN-41. Using computational analysis, structural biology, and in vivo studies in worms and human cells, we find that a positively charged pocket, specific to the NHL domain of LIN-41 and its homologs (collectively LIN41), recognizes a stem-loop RNA element, whose shape determines the binding specificity. Surprisingly, the mechanism of RNA recognition by LIN41 is drastically different from that of its more distant relative, the fly Brat. Our phylogenetic analysis suggests that this reflects a rapid evolution of the domain, presenting an interesting example of a conserved protein fold that acquired completely different solutions to RNA recognition.

  17. Space moving target detection using time domain feature

    NASA Astrophysics Data System (ADS)

    Wang, Min; Chen, Jin-yong; Gao, Feng; Zhao, Jin-yu

    2018-01-01

    The traditional space target detection methods mainly use the spatial characteristics of the star map to detect the targets, which can not make full use of the time domain information. This paper presents a new space moving target detection method based on time domain features. We firstly construct the time spectral data of star map, then analyze the time domain features of the main objects (target, stars and the background) in star maps, finally detect the moving targets using single pulse feature of the time domain signal. The real star map target detection experimental results show that the proposed method can effectively detect the trajectory of moving targets in the star map sequence, and the detection probability achieves 99% when the false alarm rate is about 8×10-5, which outperforms those of compared algorithms.

  18. Structure of the PSD-95/MAP1A complex reveals a unique target recognition mode of the MAGUK GK domain.

    PubMed

    Xia, Yitian; Shang, Yuan; Zhang, Rongguang; Zhu, Jinwei

    2017-08-10

    The PSD-95 family of membrane-associated guanylate kinases (MAGUKs) are major synaptic scaffold proteins and play crucial roles in the dynamic regulation of dendritic remodelling, which is understood to be the foundation of synaptogenesis and synaptic plasticity. The guanylate kinase (GK) domain of MAGUK family proteins functions as a phosphor-peptide binding module. However, the GK domain of PSD-95 has been found to directly bind to a peptide sequence within the C-terminal region of neuronal-specific microtubule-associated protein 1A (MAP1A), although the detailed molecular mechanism governing this phosphorylation-independent interaction at the atomic level is missing. In the present study, we determine the crystal structure of PSD-95 GK in complex with the MAP1A peptide at 2.6-Å resolution. The complex structure reveals that, unlike a linear and elongated conformation in the phosphor-peptide/GK complexes, the MAP1A peptide adopts a unique conformation with a stretch of hydrophobic residues far from each other in the primary sequence clustering and interacting with the 'hydrophobic site' of PSD-95 GK and a highly conserved aspartic acid of MAP1A (D2117) mimicking the phosphor-serine/threonine in binding to the 'phosphor-site' of PSD-95 GK. We demonstrate that the MAP1A peptide may undergo a conformational transition upon binding to PSD-95 GK. Further structural comparison of known DLG GK-mediated complexes reveals the target recognition specificity and versatility of DLG GKs. © 2017 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.

  19. 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.

  20. Novel aspects of sialoglycan recognition by the Siglec-like domains of streptococcal SRR glycoproteins.

    PubMed

    Bensing, Barbara A; Khedri, Zahra; Deng, Lingquan; Yu, Hai; Prakobphol, Akraporn; Fisher, Susan J; Chen, Xi; Iverson, Tina M; Varki, Ajit; Sullam, Paul M

    2016-11-01

    Serine-rich repeat glycoproteins are adhesins expressed by commensal and pathogenic Gram-positive bacteria. A subset of these adhesins, expressed by oral streptococci, binds sialylated glycans decorating human salivary mucin MG2/MUC7, and platelet glycoprotein GPIb. Specific sialoglycan targets were previously identified for the ligand-binding regions (BRs) of GspB and Hsa, two serine-rich repeat glycoproteins expressed by Streptococcus gordonii While GspB selectively binds sialyl-T antigen, Hsa displays broader specificity. Here we examine the binding properties of four additional BRs from Streptococcus sanguinis or Streptococcus mitis and characterize the molecular determinants of ligand selectivity and affinity. Each BR has two domains that are essential for sialoglycan binding by GspB. One domain is structurally similar to the glycan-binding module of mammalian Siglecs (sialic acid-binding immunoglobulin-like lectins), including an arginine residue that is critical for glycan recognition, and that resides within a novel, conserved YTRY motif. Despite low sequence similarity to GspB, one of the BRs selectively binds sialyl-T antigen. Although the other three BRs are highly similar to Hsa, each displayed a unique ligand repertoire, including differential recognition of sialyl Lewis antigens and sulfated glycans. These differences in glycan selectivity were closely associated with differential binding to salivary and platelet glycoproteins. Specificity of sialoglycan adherence is likely an evolving trait that may influence the propensity of streptococci expressing Siglec-like adhesins to cause infective endocarditis. Published by Oxford University Press 2016. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  1. Target recognitions in multiple-camera closed-circuit television using color constancy

    NASA Astrophysics Data System (ADS)

    Soori, Umair; Yuen, Peter; Han, Ji Wen; Ibrahim, Izzati; Chen, Wentao; Hong, Kan; Merfort, Christian; James, David; Richardson, Mark

    2013-04-01

    People tracking in crowded scenes from closed-circuit television (CCTV) footage has been a popular and challenging task in computer vision. Due to the limited spatial resolution in the CCTV footage, the color of people's dress may offer an alternative feature for their recognition and tracking. However, there are many factors, such as variable illumination conditions, viewing angles, and camera calibration, that may induce illusive modification of intrinsic color signatures of the target. Our objective is to recognize and track targets in multiple camera views using color as the detection feature, and to understand if a color constancy (CC) approach may help to reduce these color illusions due to illumination and camera artifacts and thereby improve target recognition performance. We have tested a number of CC algorithms using various color descriptors to assess the efficiency of target recognition from a real multicamera Imagery Library for Intelligent Detection Systems (i-LIDS) data set. Various classifiers have been used for target detection, and the figure of merit to assess the efficiency of target recognition is achieved through the area under the receiver operating characteristics (AUROC). We have proposed two modifications of luminance-based CC algorithms: one with a color transfer mechanism and the other using a pixel-wise sigmoid function for an adaptive dynamic range compression, a method termed enhanced luminance reflectance CC (ELRCC). We found that both algorithms improve the efficiency of target recognitions substantially better than that of the raw data without CC treatment, and in some cases the ELRCC improves target tracking by over 100% within the AUROC assessment metric. The performance of the ELRCC has been assessed over 10 selected targets from three different camera views of the i-LIDS footage, and the averaged target recognition efficiency over all these targets is found to be improved by about 54% in AUROC after the data are processed by

  2. DOMAIN MISMATCH COMPENSATION FOR SPEAKER RECOGNITION USING A LIBRARY OF WHITENERS

    DTIC Science & Technology

    2015-05-29

    DOMAIN MISMATCH COMPENSATION FOR SPEAKER RECOGNITION USING A LIBRARY OF WHITENERS Elliot Singer and Douglas Reynolds Massachusetts Institute of...development data is assumed to be unavailable. The method is based on a generalization of data whitening used in association with i-vector length...normalization and utilizes a library of whitening transforms trained at system development time using strictly out-of-domain data. The approach is

  3. Structural basis of DNA target recognition by the B3 domain of Arabidopsis epigenome reader VAL1

    PubMed Central

    Sasnauskas, Giedrius; Kauneckaitė, Kotryna; Siksnys, Virginijus

    2018-01-01

    Abstract Arabidopsis thaliana requires a prolonged period of cold exposure during winter to initiate flowering in a process termed vernalization. Exposure to cold induces epigenetic silencing of the FLOWERING LOCUS C (FLC) gene by Polycomb group (PcG) proteins. A key role in this epigenetic switch is played by transcriptional repressors VAL1 and VAL2, which specifically recognize Sph/RY DNA sequences within FLC via B3 DNA binding domains, and mediate recruitment of PcG silencing machinery. To understand the structural mechanism of site-specific DNA recognition by VAL1, we have solved the crystal structure of VAL1 B3 domain (VAL1-B3) bound to a 12 bp oligoduplex containing the canonical Sph/RY DNA sequence 5′-CATGCA-3′/5′-TGCATG-3′. We find that VAL1-B3 makes H-bonds and van der Waals contacts to DNA bases of all six positions of the canonical Sph/RY element. In agreement with the structure, in vitro DNA binding studies show that VAL1-B3 does not tolerate substitutions at any position of the 5′-TGCATG-3′ sequence. The VAL1-B3–DNA structure presented here provides a structural model for understanding the specificity of plant B3 domains interacting with the Sph/RY and other DNA sequences. PMID:29660015

  4. 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

  5. Cross-domain expression recognition based on sparse coding and transfer learning

    NASA Astrophysics Data System (ADS)

    Yang, Yong; Zhang, Weiyi; Huang, Yong

    2017-05-01

    Traditional facial expression recognition methods usually assume that the training set and the test set are independent and identically distributed. However, in actual expression recognition applications, the conditions of independent and identical distribution are hardly satisfied for the training set and test set because of the difference of light, shade, race and so on. In order to solve this problem and improve the performance of expression recognition in the actual applications, a novel method based on transfer learning and sparse coding is applied to facial expression recognition. First of all, a common primitive model, that is, the dictionary is learnt. Then, based on the idea of transfer learning, the learned primitive pattern is transferred to facial expression and the corresponding feature representation is obtained by sparse coding. The experimental results in CK +, JAFFE and NVIE database shows that the transfer learning based on sparse coding method can effectively improve the expression recognition rate in the cross-domain expression recognition task and is suitable for the practical facial expression recognition applications.

  6. Structural Mechanism of the Oxygenase JMJD6 Recognition by the Extraterminal (ET) Domain of BRD4.

    PubMed

    Konuma, Tsuyoshi; Yu, Di; Zhao, Chengcheng; Ju, Ying; Sharma, Rajal; Ren, Chunyan; Zhang, Qiang; Zhou, Ming-Ming; Zeng, Lei

    2017-11-24

    Jumonji domain-containing protein 6 (JMJD6) is a member of the Jumonji C family of Fe(II) and 2-oxoglutarate (2OG) dependent oxygenases. It possesses unique bi-functional oxygenase activities, acting as both an arginine demethylase and a lysyl-hydroxylase. JMJD6 has been reported to be over-expressed in oral, breast, lung, and colon cancers and plays important roles in regulation of transcription through interactions with transcription regulator BRD4, histones, U2AF65, Luc7L3, and SRSF11. Here, we report a structural mechanism revealed by NMR of JMJD6 recognition by the extraterminal (ET) domain of BRD4 in that a JMJD6 peptide (Lys84-Asn96) adapts an α-helix when bound to the ET domain. This intermolecular recognition is established through JMJD6 interactions with the conserved hydrophobic core of the ET domain, and reinforced by electrostatic interactions of JMJD6 with residues in the inter-helical α1-α2 loop of the ET domain. Notably, this mode of ligand recognition is different from that of ET domain recognition of NSD3, LANA of herpesvirus, and integrase of MLV, which involves formation of an intermolecular amphipathic two- or three- strand antiparallel β sheet. Furthermore, we demonstrate that the association between the BRD4 ET domain and JMJD6 likely requires a protein conformational change induced by single-stranded RNA binding.

  7. Feature-based RNN target recognition

    NASA Astrophysics Data System (ADS)

    Bakircioglu, Hakan; Gelenbe, Erol

    1998-09-01

    Detection and recognition of target signatures in sensory data obtained by synthetic aperture radar (SAR), forward- looking infrared, or laser radar, have received considerable attention in the literature. In this paper, we propose a feature based target classification methodology to detect and classify targets in cluttered SAR images, that makes use of selective signature data from sensory data, together with a neural network technique which uses a set of trained networks based on the Random Neural Network (RNN) model (Gelenbe 89, 90, 91, 93) which is trained to act as a matched filter. We propose and investigate radial features of target shapes that are invariant to rotation, translation, and scale, to characterize target and clutter signatures. These features are then used to train a set of learning RNNs which can be used to detect targets within clutter with high accuracy, and to classify the targets or man-made objects from natural clutter. Experimental data from SAR imagery is used to illustrate and validate the proposed method, and to calculate Receiver Operating Characteristics which illustrate the performance of the proposed algorithm.

  8. Diversity in peptide recognition by the SH2 domain of SH2B1.

    PubMed

    McKercher, Marissa A; Guan, Xiaoyang; Tan, Zhongping; Wuttke, Deborah S

    2018-02-01

    SH2B1 is a multidomain protein that serves as a key adaptor to regulate numerous cellular events, such as insulin, leptin, and growth hormone signaling pathways. Many of these protein-protein interactions are mediated by the SH2 domain of SH2B1, which recognizes ligands containing a phosphorylated tyrosine (pY), including peptides derived from janus kinase 2, insulin receptor, and insulin receptor substrate-1 and -2. Specificity for the SH2 domain of SH2B1 is conferred in these ligands either by a hydrophobic or an acidic side chain at the +3 position C-terminal to the pY. This specificity for chemically disparate species suggests that SH2B1 relies on distinct thermodynamic or structural mechanisms to bind to peptides. Using binding and structural strategies, we have identified unique thermodynamic signatures for each peptide binding mode, and several SH2B1 residues, including K575 and R578, that play distinct roles in peptide binding. The high-resolution structure of the SH2 domain of SH2B1 further reveals conformationally plastic protein loops that may contribute to the ability of the protein to recognize dissimilar ligands. Together, numerous hydrophobic and electrostatic interactions, in addition to backbone conformational flexibility, permit the recognition of diverse peptides by SH2B1. An understanding of this expanded peptide recognition will allow for the identification of novel physiologically relevant SH2B1/peptide interactions, which can contribute to the design of obesity and diabetes pharmaceuticals to target the ligand-binding interface of SH2B1 with high specificity. © 2017 Wiley Periodicals, Inc.

  9. Infrared and visible fusion face recognition based on NSCT domain

    NASA Astrophysics Data System (ADS)

    Xie, Zhihua; Zhang, Shuai; Liu, Guodong; Xiong, Jinquan

    2018-01-01

    Visible face recognition systems, being vulnerable to illumination, expression, and pose, can not achieve robust performance in unconstrained situations. Meanwhile, near infrared face images, being light- independent, can avoid or limit the drawbacks of face recognition in visible light, but its main challenges are low resolution and signal noise ratio (SNR). Therefore, near infrared and visible fusion face recognition has become an important direction in the field of unconstrained face recognition research. In this paper, a novel fusion algorithm in non-subsampled contourlet transform (NSCT) domain is proposed for Infrared and visible face fusion recognition. Firstly, NSCT is used respectively to process the infrared and visible face images, which exploits the image information at multiple scales, orientations, and frequency bands. Then, to exploit the effective discriminant feature and balance the power of high-low frequency band of NSCT coefficients, the local Gabor binary pattern (LGBP) and Local Binary Pattern (LBP) are applied respectively in different frequency parts to obtain the robust representation of infrared and visible face images. Finally, the score-level fusion is used to fuse the all the features for final classification. The visible and near infrared face recognition is tested on HITSZ Lab2 visible and near infrared face database. Experiments results show that the proposed method extracts the complementary features of near-infrared and visible-light images and improves the robustness of unconstrained face recognition.

  10. Target recognition and phase acquisition by using incoherent digital holographic imaging

    NASA Astrophysics Data System (ADS)

    Lee, Munseob; Lee, Byung-Tak

    2017-05-01

    In this study, we proposed the Incoherent Digital Holographic Imaging (IDHI) for recognition and phase information of dedicated target. Although recent development of a number of target recognition techniques such as LIDAR, there have limited success in target discrimination, in part due to low-resolution, low scanning speed, and computation power. In the paper, the proposed system consists of the incoherent light source, such as LED, Michelson interferometer, and digital CCD for acquisition of four phase shifting image. First of all, to compare with relative coherence, we used a source as laser and LED, respectively. Through numerical reconstruction by using the four phase shifting method and Fresnel diffraction method, we recovered the intensity and phase image of USAF resolution target apart from about 1.0m distance. In this experiment, we show 1.2 times improvement in resolution compared to conventional imaging. Finally, to confirm the recognition result of camouflaged targets with the same color from background, we carry out to test holographic imaging in incoherent light. In this result, we showed the possibility of a target detection and recognition that used three dimensional shape and size signatures, numerical distance from phase information of obtained holographic image.

  11. Emotionally conditioning the target-speech voice enhances recognition of the target speech under "cocktail-party" listening conditions.

    PubMed

    Lu, Lingxi; Bao, Xiaohan; Chen, Jing; Qu, Tianshu; Wu, Xihong; Li, Liang

    2018-05-01

    Under a noisy "cocktail-party" listening condition with multiple people talking, listeners can use various perceptual/cognitive unmasking cues to improve recognition of the target speech against informational speech-on-speech masking. One potential unmasking cue is the emotion expressed in a speech voice, by means of certain acoustical features. However, it was unclear whether emotionally conditioning a target-speech voice that has none of the typical acoustical features of emotions (i.e., an emotionally neutral voice) can be used by listeners for enhancing target-speech recognition under speech-on-speech masking conditions. In this study we examined the recognition of target speech against a two-talker speech masker both before and after the emotionally neutral target voice was paired with a loud female screaming sound that has a marked negative emotional valence. The results showed that recognition of the target speech (especially the first keyword in a target sentence) was significantly improved by emotionally conditioning the target speaker's voice. Moreover, the emotional unmasking effect was independent of the unmasking effect of the perceived spatial separation between the target speech and the masker. Also, (skin conductance) electrodermal responses became stronger after emotional learning when the target speech and masker were perceptually co-located, suggesting an increase of listening efforts when the target speech was informationally masked. These results indicate that emotionally conditioning the target speaker's voice does not change the acoustical parameters of the target-speech stimuli, but the emotionally conditioned vocal features can be used as cues for unmasking target speech.

  12. Target Recognition Using Neural Networks for Model Deformation Measurements

    NASA Technical Reports Server (NTRS)

    Ross, Richard W.; Hibler, David L.

    1999-01-01

    Optical measurements provide a non-invasive method for measuring deformation of wind tunnel models. Model deformation systems use targets mounted or painted on the surface of the model to identify known positions, and photogrammetric methods are used to calculate 3-D positions of the targets on the model from digital 2-D images. Under ideal conditions, the reflective targets are placed against a dark background and provide high-contrast images, aiding in target recognition. However, glints of light reflecting from the model surface, or reduced contrast caused by light source or model smoothness constraints, can compromise accurate target determination using current algorithmic methods. This paper describes a technique using a neural network and image processing technologies which increases the reliability of target recognition systems. Unlike algorithmic methods, the neural network can be trained to identify the characteristic patterns that distinguish targets from other objects of similar size and appearance and can adapt to changes in lighting and environmental conditions.

  13. Slp-76 is a critical determinant of NK-cell mediated recognition of missing-self targets.

    PubMed

    Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

    2015-07-01

    Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying "missing-self" recognition, including the involvement of activating receptors, remain poorly understood. Using ethyl-N-nitrosourea mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell mediated recognition and elimination of "missing-self" targets. The causative mutation was linked to chromosome 11 and identified as a missense mutation (Thr428Ile) in the SH2 domain of Slp-76-a critical adapter molecule downstream of ITAM-containing surface receptors. The Slp-76 Ace mutation behaved as a hypomorphic allele-while no major defects were observed in conventional T-cell development/function, a marked defect in NK cell mediated elimination of β2-microglobulin (β2M) deficient target cells was observed. Further studies revealed Slp-76 to control NK-cell receptor expression and maturation; however, activation of Slp-76(ace/ace) NK cells through ITAM-containing NK-cell receptors or allogeneic/tumor target cells appeared largely unaffected. Imagestream analysis of the NK-β2M(-/-) target cell synapse revealed a specific defect in actin recruitment to the conjugate synapse in Slp-76(ace/ace) NK cells. Overall these studies establish Slp-76 as a critical determinant of NK-cell development and NK cell mediated elimination of missing-self target cells in mice. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Slp-76 is a critical determinant of NK cell-mediated recognition of missing-self targets

    PubMed Central

    Lampe, Kristin; Endale, Mehari; Cashman, Siobhan; Fang, Hao; Mattner, Jochen; Hildeman, David; Hoebe, Kasper

    2015-01-01

    Absence of MHC class I expression is an important mechanism by which NK cells recognize a variety of target cells, yet the pathways underlying “missing-self” recognition, including the involvement of activating receptors, remain poorly understood. Using ENU mutagenesis in mice, we identified a germline mutant, designated Ace, with a marked defect in NK cell-mediated recognition and elimination of “missing-self” targets. The causative mutation was linked to chromosome 11 and identified as a missense mutation [Thr428Ile] in the SH2 domain of Slp-76—a critical adapter molecule downstream of ITAM-containing surface receptors. The Slp-76 Ace mutation behaved as a hypomorphic allele—while no major defects were observed in conventional T cell development/function, a marked defect in NK cell-mediated elimination of β2-Microglobulin (β2M)-deficient target cells was observed. Further studies revealed Slp-76 to control NK cell receptor expression and maturation, however, activation of Slp-76ace/ace NK cells through ITAM-containing NK cell receptors or allogeneic/tumor target cells appeared largely unaffected. Imagestream analysis of the NK-β2M−/− target cell synapse, revealed a specific defect in actin recruitment to the conjugate synapse in Slp-76ace/ace NK cells. Overall these studies establish Slp-76 as a critical determinant of NK cell development and NK cell-mediated elimination of missing-self target cells. PMID:25929249

  15. Target recognition of ladar range images using even-order Zernike moments.

    PubMed

    Liu, Zheng-Jun; Li, Qi; Xia, Zhi-Wei; Wang, Qi

    2012-11-01

    Ladar range images have attracted considerable attention in automatic target recognition fields. In this paper, Zernike moments (ZMs) are applied to classify the target of the range image from an arbitrary azimuth angle. However, ZMs suffer from high computational costs. To improve the performance of target recognition based on small samples, even-order ZMs with serial-parallel backpropagation neural networks (BPNNs) are applied to recognize the target of the range image. It is found that the rotation invariance and classified performance of the even-order ZMs are both better than for odd-order moments and for moments compressed by principal component analysis. The experimental results demonstrate that combining the even-order ZMs with serial-parallel BPNNs can significantly improve the recognition rate for small samples.

  16. Application of automatic threshold in dynamic target recognition with low contrast

    NASA Astrophysics Data System (ADS)

    Miao, Hua; Guo, Xiaoming; Chen, Yu

    2014-11-01

    Hybrid photoelectric joint transform correlator can realize automatic real-time recognition with high precision through the combination of optical devices and electronic devices. When recognizing targets with low contrast using photoelectric joint transform correlator, because of the difference of attitude, brightness and grayscale between target and template, only four to five frames of dynamic targets can be recognized without any processing. CCD camera is used to capture the dynamic target images and the capturing speed of CCD is 25 frames per second. Automatic threshold has many advantages like fast processing speed, effectively shielding noise interference, enhancing diffraction energy of useful information and better reserving outline of target and template, so this method plays a very important role in target recognition with optical correlation method. However, the automatic obtained threshold by program can not achieve the best recognition results for dynamic targets. The reason is that outline information is broken to some extent. Optimal threshold is obtained by manual intervention in most cases. Aiming at the characteristics of dynamic targets, the processing program of improved automatic threshold is finished by multiplying OTSU threshold of target and template by scale coefficient of the processed image, and combining with mathematical morphology. The optimal threshold can be achieved automatically by improved automatic threshold processing for dynamic low contrast target images. The recognition rate of dynamic targets is improved through decreased background noise effect and increased correlation information. A series of dynamic tank images with the speed about 70 km/h are adapted as target images. The 1st frame of this series of tanks can correlate only with the 3rd frame without any processing. Through OTSU threshold, the 80th frame can be recognized. By automatic threshold processing of the joint images, this number can be increased to 89 frames

  17. Diagnostic nanoparticle targeting of the EGF-receptor in complex biological conditions using single-domain antibodies.

    PubMed

    Zarschler, K; Prapainop, K; Mahon, E; Rocks, L; Bramini, M; Kelly, P M; Stephan, H; Dawson, K A

    2014-06-07

    For effective localization of functionalized nanoparticles at diseased tissues such as solid tumours or metastases through biorecognition, appropriate targeting vectors directed against selected tumour biomarkers are a key prerequisite. The diversity of such vector molecules ranges from proteins, including antibodies and fragments thereof, through aptamers and glycans to short peptides and small molecules. Here, we analyse the specific nanoparticle targeting capabilities of two previously suggested peptides (D4 and GE11) and a small camelid single-domain antibody (sdAb), representing potential recognition agents for the epidermal growth factor receptor (EGFR). We investigate specificity by way of receptor RNA silencing techniques and look at increasing complexity in vitro by introducing increasing concentrations of human or bovine serum. Peptides D4 and GE11 proved problematic to employ and conjugation resulted in non-receptor specific uptake into cells. Our results show that sdAb-functionalized particles can effectively target the EGFR, even in more complex bovine and human serum conditions where targeting specificity is largely conserved for increasing serum concentration. In human serum however, an inhibition of overall nanoparticle uptake is observed with increasing protein concentration. For highly affine targeting ligands such as sdAbs, targeting a receptor such as EGFR with low serum competitor abundance, receptor recognition function can still be partially realised in complex conditions. Here, we stress the value of evaluating the targeting efficiency of nanoparticle constructs in realistic biological milieu, prior to more extensive in vivo studies.

  18. Target recognition of log-polar ladar range images using moment invariants

    NASA Astrophysics Data System (ADS)

    Xia, Wenze; Han, Shaokun; Cao, Jie; Yu, Haoyong

    2017-01-01

    The ladar range image has received considerable attentions in the automatic target recognition field. However, previous research does not cover target recognition using log-polar ladar range images. Therefore, we construct a target recognition system based on log-polar ladar range images in this paper. In this system combined moment invariants and backpropagation neural network are selected as shape descriptor and shape classifier, respectively. In order to fully analyze the effect of log-polar sampling pattern on recognition result, several comparative experiments based on simulated and real range images are carried out. Eventually, several important conclusions are drawn: (i) if combined moments are computed directly by log-polar range images, translation, rotation and scaling invariant properties of combined moments will be invalid (ii) when object is located in the center of field of view, recognition rate of log-polar range images is less sensitive to the changing of field of view (iii) as object position changes from center to edge of field of view, recognition performance of log-polar range images will decline dramatically (iv) log-polar range images has a better noise robustness than Cartesian range images. Finally, we give a suggestion that it is better to divide field of view into recognition area and searching area in the real application.

  19. The RNA recognition motif domains of RBM5 are required for RNA binding and cancer cell proliferation inhibition

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

    Zhang, Lei; Zhang, Qing; Yang, Yu

    Highlights: • RNA recognition motif domains of RBM5 are essential for cell proliferation inhibition. • RNA recognition motif domains of RBM5 are essential for apoptosis induction. • RNA recognition motif domains of RBM5 are essential for RNA binding. • RNA recognition motif domains of RBM5 are essential for caspase-2 alternative splicing. - Abstract: RBM5 is a known putative tumor suppressor gene that has been shown to function in cell growth inhibition by modulating apoptosis. RBM5 also plays a critical role in alternative splicing as an RNA binding protein. However, it is still unclear which domains of RBM5 are required formore » RNA binding and related functional activities. We hypothesized the two putative RNA recognition motif (RRM) domains of RBM5 spanning from amino acids 98–178 and 231–315 are essential for RBM5-mediated cell growth inhibition, apoptosis regulation, and RNA binding. To investigate this hypothesis, we evaluated the activities of the wide-type and mutant RBM5 gene transfer in low-RBM5 expressing A549 cells. We found that, unlike wild-type RBM5 (RBM5-wt), a RBM5 mutant lacking the two RRM domains (RBM5-ΔRRM), is unable to bind RNA, has compromised caspase-2 alternative splicing activity, lacks cell proliferation inhibition and apoptosis induction function in A549 cells. These data provide direct evidence that the two RRM domains of RBM5 are required for RNA binding and the RNA binding activity of RBM5 contributes to its function on apoptosis induction and cell growth inhibition.« less

  20. Multi-Stage System for Automatic Target Recognition

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

    A multi-stage automated target recognition (ATR) system has been designed to perform computer vision tasks with adequate proficiency in mimicking human vision. The system is able to detect, identify, and track targets of interest. Potential regions of interest (ROIs) are first identified by the detection stage using an Optimum Trade-off Maximum Average Correlation Height (OT-MACH) filter combined with a wavelet transform. False positives are then eliminated by the verification stage using feature extraction methods in conjunction with neural networks. Feature extraction transforms the ROIs using filtering and binning algorithms to create feature vectors. A feedforward back-propagation neural network (NN) is then trained to classify each feature vector and to remove false positives. The system parameter optimizations process has been developed to adapt to various targets and datasets. The objective was to design an efficient computer vision system that can learn to detect multiple targets in large images with unknown backgrounds. Because the target size is small relative to the image size in this problem, there are many regions of the image that could potentially contain the target. A cursory analysis of every region can be computationally efficient, but may yield too many false positives. On the other hand, a detailed analysis of every region can yield better results, but may be computationally inefficient. The multi-stage ATR system was designed to achieve an optimal balance between accuracy and computational efficiency by incorporating both models. The detection stage first identifies potential ROIs where the target may be present by performing a fast Fourier domain OT-MACH filter-based correlation. Because threshold for this stage is chosen with the goal of detecting all true positives, a number of false positives are also detected as ROIs. The verification stage then transforms the regions of interest into feature space, and eliminates false positives using an

  1. Cat-eye effect target recognition with single-pixel detectors

    NASA Astrophysics Data System (ADS)

    Jian, Weijian; Li, Li; Zhang, Xiaoyue

    2015-12-01

    A prototype of cat-eye effect target recognition with single-pixel detectors is proposed. Based on the framework of compressive sensing, it is possible to recognize cat-eye effect targets by projecting a series of known random patterns and measuring the backscattered light with three single-pixel detectors in different locations. The prototype only requires simpler, less expensive detectors and extends well beyond the visible spectrum. The simulations are accomplished to evaluate the feasibility of the proposed prototype. We compared our results to that obtained from conventional cat-eye effect target recognition methods using area array sensor. The experimental results show that this method is feasible and superior to the conventional method in dynamic and complicated backgrounds.

  2. Model-based recognition of 3D articulated target using ladar range data.

    PubMed

    Lv, Dan; Sun, Jian-Feng; Li, Qi; Wang, Qi

    2015-06-10

    Ladar is suitable for 3D target recognition because ladar range images can provide rich 3D geometric surface information of targets. In this paper, we propose a part-based 3D model matching technique to recognize articulated ground military vehicles in ladar range images. The key of this approach is to solve the decomposition and pose estimation of articulated parts of targets. The articulated components were decomposed into isolate parts based on 3D geometric properties of targets, such as surface point normals, data histogram distribution, and data distance relationships. The corresponding poses of these separate parts were estimated through the linear characteristics of barrels. According to these pose parameters, all parts of the target were roughly aligned to 3D point cloud models in a library and fine matching was finally performed to accomplish 3D articulated target recognition. The recognition performance was evaluated with 1728 ladar range images of eight different articulated military vehicles with various part types and orientations. Experimental results demonstrated that the proposed approach achieved a high recognition rate.

  3. Stability and Sugar Recognition Ability of Ricin-Like Carbohydrate Binding Domains

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

    Yao, Jianzhuang; Nellas, Ricky B; Glover, Mary M

    2011-01-01

    Lectins are a class of proteins known for their novel binding to saccharides. Understanding this sugar recognition process can be crucial in creating structure-based designs of proteins with various biological roles. We focus on the sugar binding of a particular lectin, ricin, which has two -trefoil carbohydrate-binding domains (CRDs) found in several plant protein toxins. The binding ability of possible sites of ricin-like CRD has been puzzling. The apo and various (multiple) ligand-bound forms of the sugar-binding domains of ricin were studied by molecular dynamics simulations. By evaluating structural stability, hydrogen bond dynamics, flexibility, and binding energy, we obtained amore » detailed picture of the sugar recognition of the ricin-like CRD. Unlike what was previously believed, we found that the binding abilities of the two known sites are not independent of each other. The binding ability of one site is positively affected by the other site. While the mean positions of different binding scenarios are not altered significantly, the flexibility of the binding pockets visibly decreases upon multiple ligand binding. This change in flexibility seems to be the origin of the binding cooperativity. All the hydrogen bonds that are strong in the monoligand state are also strong in the double-ligand complex, although the stability is much higher in the latter form due to cooperativity. These strong hydrogen bonds in a monoligand state are deemed to be the essential hydrogen bonds. Furthermore, by examining the structural correlation matrix, the two domains are structurally one entity. Galactose hydroxyl groups, OH4 and OH3, are the most critical parts in both site 1 and site 2 recognition.« less

  4. Object recognition of real targets using modelled SAR images

    NASA Astrophysics Data System (ADS)

    Zherdev, D. A.

    2017-12-01

    In this work the problem of recognition is studied using SAR images. The algorithm of recognition is based on the computation of conjugation indices with vectors of class. The support subspaces for each class are constructed by exception of the most and the less correlated vectors in a class. In the study we examine the ability of a significant feature vector size reduce that leads to recognition time decrease. The images of targets form the feature vectors that are transformed using pre-trained convolutional neural network (CNN).

  5. Entity recognition in the biomedical domain using a hybrid approach.

    PubMed

    Basaldella, Marco; Furrer, Lenz; Tasso, Carlo; Rinaldi, Fabio

    2017-11-09

    This article describes a high-recall, high-precision approach for the extraction of biomedical entities from scientific articles. The approach uses a two-stage pipeline, combining a dictionary-based entity recognizer with a machine-learning classifier. First, the OGER entity recognizer, which has a bias towards high recall, annotates the terms that appear in selected domain ontologies. Subsequently, the Distiller framework uses this information as a feature for a machine learning algorithm to select the relevant entities only. For this step, we compare two different supervised machine-learning algorithms: Conditional Random Fields and Neural Networks. In an in-domain evaluation using the CRAFT corpus, we test the performance of the combined systems when recognizing chemicals, cell types, cellular components, biological processes, molecular functions, organisms, proteins, and biological sequences. Our best system combines dictionary-based candidate generation with Neural-Network-based filtering. It achieves an overall precision of 86% at a recall of 60% on the named entity recognition task, and a precision of 51% at a recall of 49% on the concept recognition task. These results are to our knowledge the best reported so far in this particular task.

  6. Software for Partly Automated Recognition of Targets

    NASA Technical Reports Server (NTRS)

    Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark; Selinsky, T.

    2002-01-01

    The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user's tendencies while the user is selecting targets and to increase the user's productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.

  7. Software for Partly Automated Recognition of Targets

    NASA Technical Reports Server (NTRS)

    Opitz, David; Blundell, Stuart; Bain, William; Morris, Matthew; Carlson, Ian; Mangrich, Mark

    2003-01-01

    The Feature Analyst is a computer program for assisted (partially automated) recognition of targets in images. This program was developed to accelerate the processing of high-resolution satellite image data for incorporation into geographic information systems (GIS). This program creates an advanced user interface that embeds proprietary machine-learning algorithms in commercial image-processing and GIS software. A human analyst provides samples of target features from multiple sets of data, then the software develops a data-fusion model that automatically extracts the remaining features from selected sets of data. The program thus leverages the natural ability of humans to recognize objects in complex scenes, without requiring the user to explain the human visual recognition process by means of lengthy software. Two major subprograms are the reactive agent and the thinking agent. The reactive agent strives to quickly learn the user s tendencies while the user is selecting targets and to increase the user s productivity by immediately suggesting the next set of pixels that the user may wish to select. The thinking agent utilizes all available resources, taking as much time as needed, to produce the most accurate autonomous feature-extraction model possible.

  8. Lune/eye gone, a Pax-like protein, uses a partial paired domain and a homeodomain for DNA recognition.

    PubMed

    Jun, S; Wallen, R V; Goriely, A; Kalionis, B; Desplan, C

    1998-11-10

    Pax proteins, characterized by the presence of a paired domain, play key regulatory roles during development. The paired domain is a bipartite DNA-binding domain that contains two helix-turn-helix domains joined by a linker region. Each of the subdomains, the PAI and RED domains, has been shown to be a distinct DNA-binding domain. The PAI domain is the most critical, but in specific circumstances, the RED domain is involved in DNA recognition. We describe a Pax protein, originally called Lune, that is the product of the Drosophila eye gone gene (eyg). It is unique among Pax proteins, because it contains only the RED domain. eyg seems to play a role both in the organogenesis of the salivary gland during embryogenesis and in the development of the eye. A high-affinity binding site for the Eyg RED domain was identified by using systematic evolution of ligands by exponential enrichment techniques. This binding site is related to a binding site previously identified for the RED domain of the Pax-6 5a isoform. Eyg also contains another DNA-binding domain, a Prd-class homeodomain (HD), whose palindromic binding site is similar to other Prd-class HDs. The ability of Pax proteins to use the PAI, RED, and HD, or combinations thereof, may be one mechanism that allows them to be used at different stages of development to regulate various developmental processes through the activation of specific target genes.

  9. Lune/eye gone, a Pax-like protein, uses a partial paired domain and a homeodomain for DNA recognition

    PubMed Central

    Jun, Susie; Wallen, Robert V.; Goriely, Anne; Kalionis, Bill; Desplan, Claude

    1998-01-01

    Pax proteins, characterized by the presence of a paired domain, play key regulatory roles during development. The paired domain is a bipartite DNA-binding domain that contains two helix–turn–helix domains joined by a linker region. Each of the subdomains, the PAI and RED domains, has been shown to be a distinct DNA-binding domain. The PAI domain is the most critical, but in specific circumstances, the RED domain is involved in DNA recognition. We describe a Pax protein, originally called Lune, that is the product of the Drosophila eye gone gene (eyg). It is unique among Pax proteins, because it contains only the RED domain. eyg seems to play a role both in the organogenesis of the salivary gland during embryogenesis and in the development of the eye. A high-affinity binding site for the Eyg RED domain was identified by using systematic evolution of ligands by exponential enrichment techniques. This binding site is related to a binding site previously identified for the RED domain of the Pax-6 5a isoform. Eyg also contains another DNA-binding domain, a Prd-class homeodomain (HD), whose palindromic binding site is similar to other Prd-class HDs. The ability of Pax proteins to use the PAI, RED, and HD, or combinations thereof, may be one mechanism that allows them to be used at different stages of development to regulate various developmental processes through the activation of specific target genes. PMID:9811867

  10. Recognition of cyclic-di-GMP by a riboswitch conducts translational repression through masking the ribosome-binding site distant from the aptamer domain.

    PubMed

    Inuzuka, Saki; Kakizawa, Hitoshi; Nishimura, Kei-Ichiro; Naito, Takuto; Miyazaki, Katsushi; Furuta, Hiroyuki; Matsumura, Shigeyoshi; Ikawa, Yoshiya

    2018-06-01

    The riboswitch is a class of RNA-based gene regulatory machinery that is dependent on recognition of its target ligand by RNA tertiary structures. Ligand recognition is achieved by the aptamer domain, and ligand-dependent structural changes of the expression platform then usually mediate termination of transcription or translational initiation. Ligand-dependent structural changes of the aptamer domain and expression platform have been reported for several riboswitches with short (<40 nucleotides) expression platforms. In this study, we characterized structural changes of the Vc2 c-di-GMP riboswitch that represses translation of downstream open reading frames in a ligand-dependent manner. The Vc2 riboswitch has a long (97 nucleotides) expression platform, but its structure and function are largely unknown. Through mutational analysis and chemical probing, we identified its secondary structures that are possibly responsible for switch-OFF and switch-ON states of translational initiation. © 2018 Molecular Biology Society of Japan and John Wiley & Sons Australia, Ltd.

  11. Understanding the molecular differential recognition of muramyl peptide ligands by LRR domains of human NOD receptors.

    PubMed

    Vijayrajratnam, Sukhithasri; Pushkaran, Anju Choorakottayil; Balakrishnan, Aathira; Vasudevan, Anil Kumar; Biswas, Raja; Mohan, Chethampadi Gopi

    2017-07-27

    Human nucleotide-binding oligomerization domain proteins, hNOD1 and hNOD2, are host intracellular receptors with C-terminal leucine-rich repeat (LRR) domains, which recognize specific bacterial peptidoglycan (PG) fragments as their ligands. The specificity of this recognition is dependent on the third amino acid of the stem peptide of the PG ligand, which is usually meso -diaminopimelic acid ( meso DAP) or l-lysine (l-Lys). Since the LRR domains of hNOD receptors had been experimentally shown to confer the PG ligand-sensing specificity, we developed three-dimensional structures of hNOD1-LRR and the hNOD2-LRR to understand the mechanism of differential recognition of muramyl peptide ligands by hNOD receptors. The hNOD1-LRR and hNOD2-LRR receptor models exhibited right-handed curved solenoid shape. The hot-spot residues experimentally proved to be critical for ligand recognition were located in the concavity of the NOD-LRR and formed the recognition site. Our molecular docking analyses and molecular electrostatic potential mapping studies explain the activation of hNOD-LRRs, in response to effective molecular interactions of PG ligands at the recognition site; and conversely, the inability of certain PG ligands to activate hNOD-LRRs, by deviations from the recognition site. Based on molecular docking studies using PG ligands, we propose few residues - G825, D826 and N850 in hNOD1-LRR and L904, G905, W931, L932 and S933 in hNOD2-LRR, evolutionarily conserved across different host species, which may play a major role in ligand recognition. Thus, our integrated experimental and computational approach elucidates the molecular basis underlying the differential recognition of PG ligands by hNOD receptors. © 2017 The Author(s); published by Portland Press Limited on behalf of the Biochemical Society.

  12. Structural insights into the regulation and the recognition of histone marks by the SET domain of NSD1

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

    Morishita, Masayo; Di Luccio, Eric, E-mail: eric.diluccio@gmail.com

    2011-08-26

    Highlights: {yields} NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 are histone methyltransferases linked to numerous cancers. {yields} Little is known about the NSD pathways and HMTase inhibitors are sorely needed in the epigenetic therapy of cancers. {yields} We investigate the regulation and the recognition of histone marks by the SET domain of NSD1. {yields} A unique and key mechanism is driven by a loop at the interface of the SET and postSET region. {yields} Implications for developing specific and selective HMTase inhibitors are presented. -- Abstract: The development of epigenetic therapies fuels cancer hope. DNA-methylation inhibitors, histone-deacetylase and histone-methyltransferase (HMTase) inhibitors are beingmore » developed as the utilization of epigenetic targets is emerging as an effective and valuable approach to chemotherapy as well as chemoprevention of cancer. The nuclear receptor binding SET domain (NSD) protein is a family of three HMTases, NSD1, NSD2/MMSET/WHSC1, and NSD3/WHSC1L1 that are critical in maintaining the chromatin integrity. A growing number of studies have reported alterations or amplifications of NSD1, NSD2, or NSD3 in numerous carcinogenic events. Reducing NSDs activity through specific lysine-HMTase inhibitors appears promising to help suppressing cancer growth. However, little is known about the NSD pathways and our understanding of the histone lysine-HMTase mechanism is partial. To shed some light on both the recognition and the regulation of epigenetic marks by the SET domain of the NSD family, we investigate the structural mechanisms of the docking of the histone-H4 tail on the SET domain of NSD1. Our finding exposes a key regulatory and recognition mechanism driven by the flexibility of a loop at the interface of the SET and postSET region. Finally, we prospect the special value of this regulatory region for developing specific and selective NSD inhibitors for the epigenetic therapy of cancers.« less

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

    PubMed Central

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

    2017-01-01

    Model training is a key technique for radar target recognition. Traditional model training algorithms in the framework of single task leaning ignore the relationships among multiple tasks, which degrades the recognition performance. In this paper, we propose a clustered multi-task learning, which can reveal and share the multi-task relationships for radar target recognition. To further make full use of these relationships, the latent multi-task relationships in the projection space are taken into consideration. Specifically, a constraint term in the projection space is proposed, the main idea of which is that multiple tasks within a close cluster should be close to each other in the projection space. In the proposed method, the cluster structures and multi-task relationships can be autonomously learned and utilized in both of the original and projected space. In view of the nonlinear characteristics of radar targets, the proposed method is extended to a non-linear kernel version and the corresponding non-linear multi-task solving method is proposed. Comprehensive experimental studies on simulated high-resolution range profile dataset and MSTAR SAR public database verify the superiority of the proposed method to some related algorithms. PMID:28953267

  14. A fusion approach for coarse-to-fine target recognition

    NASA Astrophysics Data System (ADS)

    Folkesson, Martin; Grönwall, Christina; Jungert, Erland

    2006-04-01

    A fusion approach in a query based information system is presented. The system is designed for querying multimedia data bases, and here applied to target recognition using heterogeneous data sources. The recognition process is coarse-to-fine, with an initial attribute estimation step and a following matching step. Several sensor types and algorithms are involved in each of these two steps. An independence of the matching results, on the origin of the estimation results, is observed. It allows for distribution of data between algorithms in an intermediate fusion step, without risk of data incest. This increases the overall chance of recognising the target. An implementation of the system is described.

  15. A robust recognition and accurate locating method for circular coded diagonal target

    NASA Astrophysics Data System (ADS)

    Bao, Yunna; Shang, Yang; Sun, Xiaoliang; Zhou, Jiexin

    2017-10-01

    As a category of special control points which can be automatically identified, artificial coded targets have been widely developed in the field of computer vision, photogrammetry, augmented reality, etc. In this paper, a new circular coded target designed by RockeTech technology Corp. Ltd is analyzed and studied, which is called circular coded diagonal target (CCDT). A novel detection and recognition method with good robustness is proposed in the paper, and implemented on Visual Studio. In this algorithm, firstly, the ellipse features of the center circle are used for rough positioning. Then, according to the characteristics of the center diagonal target, a circular frequency filter is designed to choose the correct center circle and eliminates non-target noise. The precise positioning of the coded target is done by the correlation coefficient fitting extreme value method. Finally, the coded target recognition is achieved by decoding the binary sequence in the outer ring of the extracted target. To test the proposed algorithm, this paper has carried out simulation experiments and real experiments. The results show that the CCDT recognition and accurate locating method proposed in this paper can robustly recognize and accurately locate the targets in complex and noisy background.

  16. Structural coupling of SH2-kinase domains links Fes and Abl substrate recognition and kinase activation.

    PubMed

    Filippakopoulos, Panagis; Kofler, Michael; Hantschel, Oliver; Gish, Gerald D; Grebien, Florian; Salah, Eidarus; Neudecker, Philipp; Kay, Lewis E; Turk, Benjamin E; Superti-Furga, Giulio; Pawson, Tony; Knapp, Stefan

    2008-09-05

    The SH2 domain of cytoplasmic tyrosine kinases can enhance catalytic activity and substrate recognition, but the molecular mechanisms by which this is achieved are poorly understood. We have solved the structure of the prototypic SH2-kinase unit of the human Fes tyrosine kinase, which appears specialized for positive signaling. In its active conformation, the SH2 domain tightly interacts with the kinase N-terminal lobe and positions the kinase alphaC helix in an active configuration through essential packing and electrostatic interactions. This interaction is stabilized by ligand binding to the SH2 domain. Our data indicate that Fes kinase activation is closely coupled to substrate recognition through cooperative SH2-kinase-substrate interactions. Similarly, we find that the SH2 domain of the active Abl kinase stimulates catalytic activity and substrate phosphorylation through a distinct SH2-kinase interface. Thus, the SH2 and catalytic domains of active Fes and Abl pro-oncogenic kinases form integrated structures essential for effective tyrosine kinase signaling.

  17. Arrhythmia Classification Based on Multi-Domain Feature Extraction for an ECG Recognition System.

    PubMed

    Li, Hongqiang; Yuan, Danyang; Wang, Youxi; Cui, Dianyin; Cao, Lu

    2016-10-20

    Automatic recognition of arrhythmias is particularly important in the diagnosis of heart diseases. This study presents an electrocardiogram (ECG) recognition system based on multi-domain feature extraction to classify ECG beats. An improved wavelet threshold method for ECG signal pre-processing is applied to remove noise interference. A novel multi-domain feature extraction method is proposed; this method employs kernel-independent component analysis in nonlinear feature extraction and uses discrete wavelet transform to extract frequency domain features. The proposed system utilises a support vector machine classifier optimized with a genetic algorithm to recognize different types of heartbeats. An ECG acquisition experimental platform, in which ECG beats are collected as ECG data for classification, is constructed to demonstrate the effectiveness of the system in ECG beat classification. The presented system, when applied to the MIT-BIH arrhythmia database, achieves a high classification accuracy of 98.8%. Experimental results based on the ECG acquisition experimental platform show that the system obtains a satisfactory classification accuracy of 97.3% and is able to classify ECG beats efficiently for the automatic identification of cardiac arrhythmias.

  18. Arrhythmia Classification Based on Multi-Domain Feature Extraction for an ECG Recognition System

    PubMed Central

    Li, Hongqiang; Yuan, Danyang; Wang, Youxi; Cui, Dianyin; Cao, Lu

    2016-01-01

    Automatic recognition of arrhythmias is particularly important in the diagnosis of heart diseases. This study presents an electrocardiogram (ECG) recognition system based on multi-domain feature extraction to classify ECG beats. An improved wavelet threshold method for ECG signal pre-processing is applied to remove noise interference. A novel multi-domain feature extraction method is proposed; this method employs kernel-independent component analysis in nonlinear feature extraction and uses discrete wavelet transform to extract frequency domain features. The proposed system utilises a support vector machine classifier optimized with a genetic algorithm to recognize different types of heartbeats. An ECG acquisition experimental platform, in which ECG beats are collected as ECG data for classification, is constructed to demonstrate the effectiveness of the system in ECG beat classification. The presented system, when applied to the MIT-BIH arrhythmia database, achieves a high classification accuracy of 98.8%. Experimental results based on the ECG acquisition experimental platform show that the system obtains a satisfactory classification accuracy of 97.3% and is able to classify ECG beats efficiently for the automatic identification of cardiac arrhythmias. PMID:27775596

  19. Testing Saliency Parameters for Automatic Target Recognition

    NASA Technical Reports Server (NTRS)

    Pandya, Sagar

    2012-01-01

    A bottom-up visual attention model (the saliency model) is tested to enhance the performance of Automated Target Recognition (ATR). JPL has developed an ATR system that identifies regions of interest (ROI) using a trained OT-MACH filter, and then classifies potential targets as true- or false-positives using machine-learning techniques. In this project, saliency is used as a pre-processing step to reduce the space for performing OT-MACH filtering. Saliency parameters, such as output level and orientation weight, are tuned to detect known target features. Preliminary results are promising and future work entails a rigrous and parameter-based search to gain maximum insight about this method.

  20. A novel rotational invariants target recognition method for rotating motion blurred images

    NASA Astrophysics Data System (ADS)

    Lan, Jinhui; Gong, Meiling; Dong, Mingwei; Zeng, Yiliang; Zhang, Yuzhen

    2017-11-01

    The imaging of the image sensor is blurred due to the rotational motion of the carrier and reducing the target recognition rate greatly. Although the traditional mode that restores the image first and then identifies the target can improve the recognition rate, it takes a long time to recognize. In order to solve this problem, a rotating fuzzy invariants extracted model was constructed that recognizes target directly. The model includes three metric layers. The object description capability of metric algorithms that contain gray value statistical algorithm, improved round projection transformation algorithm and rotation-convolution moment invariants in the three metric layers ranges from low to high, and the metric layer with the lowest description ability among them is as the input which can eliminate non pixel points of target region from degenerate image gradually. Experimental results show that the proposed model can improve the correct target recognition rate of blurred image and optimum allocation between the computational complexity and function of region.

  1. Radioligand Recognition of Insecticide Targets.

    PubMed

    Casida, John E

    2018-04-04

    Insecticide radioligands allow the direct recognition and analysis of the targets and mechanisms of toxic action critical to effective and safe pest control. These radioligands are either the insecticides themselves or analogs that bind at the same or coupled sites. Preferred radioligands and their targets, often in both insects and mammals, are trioxabicyclooctanes for the γ-aminobutyric acid (GABA) receptor, avermectin for the glutamate receptor, imidacloprid for the nicotinic receptor, ryanodine and chlorantraniliprole for the ryanodine receptor, and rotenone or pyridaben for NADH + ubiquinone oxidoreductase. Pyrethroids and other Na + channel modulator insecticides are generally poor radioligands due to lipophilicity and high nonspecific binding. For target site validation, the structure-activity relationships competing with the radioligand in the binding assays should be the same as that for insecticidal activity or toxicity except for rapidly detoxified or proinsecticide analogs. Once the radioligand assay is validated for relevance, it will often help define target site modifications on selection of resistant pest strains, selectivity between insects and mammals, and interaction with antidotes and other chemicals at modulator sites. Binding assays also serve for receptor isolation and photoaffinity labeling to characterize the interactions involved.

  2. On-chip learning of hyper-spectral data for real time target recognition

    NASA Technical Reports Server (NTRS)

    Duong, T. A.; Daud, T.; Thakoor, A.

    2000-01-01

    As the focus of our present paper, we have used the cascade error projection (CEP) learning algorithm (shown to be hardware-implementable) with on-chip learning (OCL) scheme to obtain three orders of magnitude speed-up in target recognition compared to software-based learning schemes. Thus, it is shown, real time learning as well as data processing for target recognition can be achieved.

  3. Gaussian mixture models-based ship target recognition algorithm in remote sensing infrared images

    NASA Astrophysics Data System (ADS)

    Yao, Shoukui; Qin, Xiaojuan

    2018-02-01

    Since the resolution of remote sensing infrared images is low, the features of ship targets become unstable. The issue of how to recognize ships with fuzzy features is an open problem. In this paper, we propose a novel ship target recognition algorithm based on Gaussian mixture models (GMMs). In the proposed algorithm, there are mainly two steps. At the first step, the Hu moments of these ship target images are calculated, and the GMMs are trained on the moment features of ships. At the second step, the moment feature of each ship image is assigned to the trained GMMs for recognition. Because of the scale, rotation, translation invariance property of Hu moments and the power feature-space description ability of GMMs, the GMMs-based ship target recognition algorithm can recognize ship reliably. Experimental results of a large simulating image set show that our approach is effective in distinguishing different ship types, and obtains a satisfactory ship recognition performance.

  4. Single-Molecule View of Small RNA-Guided Target Search and Recognition.

    PubMed

    Globyte, Viktorija; Kim, Sung Hyun; Joo, Chirlmin

    2018-05-20

    Most everyday processes in life involve a necessity for an entity to locate its target. On a cellular level, many proteins have to find their target to perform their function. From gene-expression regulation to DNA repair to host defense, numerous nucleic acid-interacting proteins use distinct target search mechanisms. Several proteins achieve that with the help of short RNA strands known as guides. This review focuses on single-molecule advances studying the target search and recognition mechanism of Argonaute and CRISPR (clustered regularly interspaced short palindromic repeats) systems. We discuss different steps involved in search and recognition, from the initial complex prearrangement into the target-search competent state to the final proofreading steps. We focus on target search mechanisms that range from weak interactions, to one- and three-dimensional diffusion, to conformational proofreading. We compare the mechanisms of Argonaute and CRISPR with a well-studied target search system, RecA.

  5. Single-domain antibody bioconjugated near-IR quantum dots for targeted cellular imaging of pancreatic cancer.

    PubMed

    Zaman, Md Badruz; Baral, Toya Nath; Jakubek, Zygmunt J; Zhang, Jianbing; Wu, Xiaohua; Lai, Edward; Whitfield, Dennis; Yu, Kui

    2011-05-01

    Successful targeted imaging of BxPC3 human pancreatic cancer cells is feasible with near-IR CdTeSe/CdS quantum dots (QDs) functionalized with single-domain antibody (sdAb) 2A3. For specific targeting, sdAbs are superior to conventional antibodies, especially in terms of stability, aggregation, and production cost. The bright CdTeSe/CdS QDs were synthesized to emit in the diagnostic window of 650-900 nm with a narrow emission band. 2A3 was derived from llama and is small in size of 13 kDa, but with fully-functional recognition to the target carcinoembryonic antigen-related cell adhesion molecule 6 (CEACAM6), a possible biomarker as a therapeutic target of pancreatic cancer. For compelling imaging, optical may be the most sensible among the various imaging modalities, regarding the sensitivity and cost. This first report on sdAb-conjugated near-IR QDs with high signal to background sensitivity for targeted cellular imaging brings insights into the development of optical molecular imaging for early stage cancer diagnosis.

  6. Activity Augmentation of Amphioxus Peptidoglycan Recognition Protein BbtPGRP3 via Fusion with a Chitin Binding Domain

    PubMed Central

    Wang, Wen-Jie; Cheng, Wang; Luo, Ming; Yan, Qingyu; Yu, Hong-Mei; Li, Qiong; Cao, Dong-Dong; Huang, Shengfeng; Xu, Anlong; Mariuzza, Roy A.; Chen, Yuxing; Zhou, Cong-Zhao

    2015-01-01

    Peptidoglycan recognition proteins (PGRPs), which have been identified in most animals, are pattern recognition molecules that involve antimicrobial defense. Resulting from extraordinary expansion of innate immune genes, the amphioxus encodes many PGRPs of diverse functions. For instance, three isoforms of PGRP encoded by Branchiostoma belcheri tsingtauense, termed BbtPGRP1~3, are fused with a chitin binding domain (CBD) at the N-terminus. Here we report the 2.7 Å crystal structure of BbtPGRP3, revealing an overall structure of an N-terminal hevein-like CBD followed by a catalytic PGRP domain. Activity assays combined with site-directed mutagenesis indicated that the individual PGRP domain exhibits amidase activity towards both DAP-type and Lys-type peptidoglycans (PGNs), the former of which is favored. The N-terminal CBD not only has the chitin-binding activity, but also enables BbtPGRP3 to gain a five-fold increase of amidase activity towards the Lys-type PGNs, leading to a significantly broadened substrate spectrum. Together, we propose that modular evolution via domain shuffling combined with gene horizontal transfer makes BbtPGRP1~3 novel PGRPs of augmented catalytic activity and broad recognition spectrum. PMID:26479246

  7. An Exquisitely Specific PDZ/Target Recognition Revealed by the Structure of INAD PDZ3 in Complex with TRP Channel Tail.

    PubMed

    Ye, Fei; Liu, Wei; Shang, Yuan; Zhang, Mingjie

    2016-03-01

    The vast majority of PDZ domains are known to bind to a few C-terminal tail residues of target proteins with modest binding affinities and specificities. Such promiscuous PDZ/target interactions are not compatible with highly specific physiological functions of PDZ domain proteins and their targets. Here, we report an unexpected PDZ/target binding occurring between the scaffold protein inactivation no afterpotential D (INAD) and transient receptor potential (TRP) channel in Drosophila photoreceptors. The C-terminal 15 residues of TRP are required for the specific interaction with INAD PDZ3. The INAD PDZ3/TRP peptide complex structure reveals that only the extreme C-terminal Leu of TRP binds to the canonical αB/βB groove of INAD PDZ3. The rest of the TRP peptide, by forming a β hairpin structure, binds to a surface away from the αB/βB groove of PDZ3 and contributes to the majority of the binding energy. Thus, the INAD PDZ3/TRP channel interaction is exquisitely specific and represents a new mode of PDZ/target recognitions. Copyright © 2016 Elsevier Ltd. All rights reserved.

  8. Combining Open-domain and Biomedical Knowledge for Topic Recognition in Consumer Health Questions.

    PubMed

    Mrabet, Yassine; Kilicoglu, Halil; Roberts, Kirk; Demner-Fushman, Dina

    2016-01-01

    Determining the main topics in consumer health questions is a crucial step in their processing as it allows narrowing the search space to a specific semantic context. In this paper we propose a topic recognition approach based on biomedical and open-domain knowledge bases. In the first step of our method, we recognize named entities in consumer health questions using an unsupervised method that relies on a biomedical knowledge base, UMLS, and an open-domain knowledge base, DBpedia. In the next step, we cast topic recognition as a binary classification problem of deciding whether a named entity is the question topic or not. We evaluated our approach on a dataset from the National Library of Medicine (NLM), introduced in this paper, and another from the Genetic and Rare Disease Information Center (GARD). The combination of knowledge bases outperformed the results obtained by individual knowledge bases by up to 16.5% F1 and achieved state-of-the-art performance. Our results demonstrate that combining open-domain knowledge bases with biomedical knowledge bases can lead to a substantial improvement in understanding user-generated health content.

  9. Online Feature Transformation Learning for Cross-Domain Object Category Recognition.

    PubMed

    Zhang, Xuesong; Zhuang, Yan; Wang, Wei; Pedrycz, Witold

    2017-06-09

    In this paper, we introduce a new research problem termed online feature transformation learning in the context of multiclass object category recognition. The learning of a feature transformation is viewed as learning a global similarity metric function in an online manner. We first consider the problem of online learning a feature transformation matrix expressed in the original feature space and propose an online passive aggressive feature transformation algorithm. Then these original features are mapped to kernel space and an online single kernel feature transformation (OSKFT) algorithm is developed to learn a nonlinear feature transformation. Based on the OSKFT and the existing Hedge algorithm, a novel online multiple kernel feature transformation algorithm is also proposed, which can further improve the performance of online feature transformation learning in large-scale application. The classifier is trained with k nearest neighbor algorithm together with the learned similarity metric function. Finally, we experimentally examined the effect of setting different parameter values in the proposed algorithms and evaluate the model performance on several multiclass object recognition data sets. The experimental results demonstrate the validity and good performance of our methods on cross-domain and multiclass object recognition application.

  10. Anodal tDCS targeting the right orbitofrontal cortex enhances facial expression recognition

    PubMed Central

    Murphy, Jillian M.; Ridley, Nicole J.; Vercammen, Ans

    2015-01-01

    The orbitofrontal cortex (OFC) has been implicated in the capacity to accurately recognise facial expressions. The aim of the current study was to determine if anodal transcranial direct current stimulation (tDCS) targeting the right OFC in healthy adults would enhance facial expression recognition, compared with a sham condition. Across two counterbalanced sessions of tDCS (i.e. anodal and sham), 20 undergraduate participants (18 female) completed a facial expression labelling task comprising angry, disgusted, fearful, happy, sad and neutral expressions, and a control (social judgement) task comprising the same expressions. Responses on the labelling task were scored for accuracy, median reaction time and overall efficiency (i.e. combined accuracy and reaction time). Anodal tDCS targeting the right OFC enhanced facial expression recognition, reflected in greater efficiency and speed of recognition across emotions, relative to the sham condition. In contrast, there was no effect of tDCS to responses on the control task. This is the first study to demonstrate that anodal tDCS targeting the right OFC boosts facial expression recognition. This finding provides a solid foundation for future research to examine the efficacy of this technique as a means to treat facial expression recognition deficits, particularly in individuals with OFC damage or dysfunction. PMID:25971602

  11. Mechanistic insights into phosphoprotein-binding FHA domains.

    PubMed

    Liang, Xiangyang; Van Doren, Steven R

    2008-08-01

    [Structure: see text]. FHA domains are protein modules that switch signals in diverse biological pathways by monitoring the phosphorylation of threonine residues of target proteins. As part of the effort to gain insight into cellular avoidance of cancer, FHA domains involved in the cellular response to DNA damage have been especially well-characterized. The complete protein where the FHA domain resides and the interaction partners determine the nature of the signaling. Thus, a key biochemical question is how do FHA domains pick out their partners from among thousands of alternatives in the cell? This Account discusses the structure, affinity, and specificity of FHA domains and the formation of their functional structure. Although FHA domains share sequence identity at only five loop residues, they all fold into a beta-sandwich of two beta-sheets. The conserved arginine and serine of the recognition loops recognize the phosphorylation of the threonine targeted. Side chains emanating from loops that join beta-strand 4 with 5, 6 with 7, or 10 with 11 make specific contacts with amino acids of the ligand that tailor sequence preferences. Many FHA domains choose a partner in extended conformation, somewhat according to the residue three after the phosphothreonine in sequence (pT + 3 position). One group of FHA domains chooses a short carboxylate-containing side chain at pT + 3. Another group chooses a long, branched aliphatic side chain. A third group prefers other hydrophobic or uncharged polar side chains at pT + 3. However, another FHA domain instead chooses on the basis of pT - 2, pT - 3, and pT + 1 positions. An FHA domain from a marker of human cancer instead chooses a much longer protein fragment that adds a beta-strand to its beta-sheet and that presents hydrophobic residues from a novel helix to the usual recognition surface. This novel recognition site and more remote sites for the binding of other types of protein partners were predicted for the entire family

  12. Autonomous target recognition using remotely sensed surface vibration measurements

    NASA Astrophysics Data System (ADS)

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

    1993-09-01

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

  13. An Autoinhibitory Role for the Pleckstrin Homology Domain of Interleukin-2-Inducible Tyrosine Kinase and Its Interplay with Canonical Phospholipid Recognition.

    PubMed

    Devkota, Sujan; Joseph, Raji E; Boyken, Scott E; Fulton, D Bruce; Andreotti, Amy H

    2017-06-13

    Pleckstrin homology (PH) domains are well-known as phospholipid binding modules, yet evidence that PH domain function extends beyond lipid recognition is mounting. In this work, we characterize a protein binding function for the PH domain of interleukin-2-inducible tyrosine kinase (ITK), an immune cell specific signaling protein that belongs to the TEC family of nonreceptor tyrosine kinases. Its N-terminal PH domain is a well-characterized lipid binding module that localizes ITK to the membrane via phosphatidylinositol 3,4,5-trisphosphate (PIP 3 ) binding. Using a combination of nuclear magnetic resonance spectroscopy and mutagenesis, we have mapped an autoregulatory protein interaction site on the ITK PH domain that makes direct contact with the catalytic kinase domain of ITK, inhibiting the phospho-transfer reaction. Moreover, we have elucidated an important interplay between lipid binding by the ITK PH domain and the stability of the autoinhibitory complex formed by full length ITK. The ITK activation loop in the kinase domain becomes accessible to phosphorylation to the exogenous kinase LCK upon binding of the ITK PH domain to PIP 3 . By clarifying the allosteric role of the ITK PH domain in controlling ITK function, we have expanded the functional repertoire of the PH domain generally and opened the door to alternative strategies to target this specific kinase in the context of immune cell signaling.

  14. The SPOR Domain, a Widely Conserved Peptidoglycan Binding Domain That Targets Proteins to the Site of Cell Division.

    PubMed

    Yahashiri, Atsushi; Jorgenson, Matthew A; Weiss, David S

    2017-07-15

    Sporulation-related repeat (SPOR) domains are small peptidoglycan (PG) binding domains found in thousands of bacterial proteins. The name "SPOR domain" stems from the fact that several early examples came from proteins involved in sporulation, but SPOR domain proteins are quite diverse and contribute to a variety of processes that involve remodeling of the PG sacculus, especially with respect to cell division. SPOR domains target proteins to the division site by binding to regions of PG devoid of stem peptides ("denuded" glycans), which in turn are enriched in septal PG by the intense, localized activity of cell wall amidases involved in daughter cell separation. This targeting mechanism sets SPOR domain proteins apart from most other septal ring proteins, which localize via protein-protein interactions. In addition to SPOR domains, bacteria contain several other PG-binding domains that can exploit features of the cell wall to target proteins to specific subcellular sites. Copyright © 2017 American Society for Microbiology.

  15. Aided target recognition processing of MUDSS sonar data

    NASA Astrophysics Data System (ADS)

    Lau, Brian; Chao, Tien-Hsin

    1998-09-01

    The Mobile Underwater Debris Survey System (MUDSS) is a collaborative effort by the Navy and the Jet Propulsion Lab to demonstrate multi-sensor, real-time, survey of underwater sites for ordnance and explosive waste (OEW). We describe the sonar processing algorithm, a novel target recognition algorithm incorporating wavelets, morphological image processing, expansion by Hermite polynomials, and neural networks. This algorithm has found all planted targets in MUDSS tests and has achieved spectacular success upon another Coastal Systems Station (CSS) sonar image database.

  16. An automatic target recognition system based on SAR image

    NASA Astrophysics Data System (ADS)

    Li, Qinfu; Wang, Jinquan; Zhao, Bo; Luo, Furen; Xu, Xiaojian

    2009-10-01

    In this paper, an automatic target recognition (ATR) system based on synthetic aperture radar (SAR) is proposed. This ATR system can play an important role in the simulation of up-to-data battlefield environment and be used in ATR research. To establish an integral and available system, the processing of SAR image was divided into four main stages which are de-noise, detection, cluster-discrimination and segment-recognition, respectively. The first three stages are used for searching region of interest (ROI). Once the ROIs are extracted, the recognition stage will be taken to compute the similarity between the ROIs and the templates in the electromagnetic simulation software National Electromagnetic Scattering Code (NESC). Due to the lack of the SAR raw data, the electromagnetic simulated images are added to the measured SAR background to simulate the battlefield environment8. The purpose of the system is to find the ROIs which can be the artificial military targets such as tanks, armored cars and so on and to categorize the ROIs into the right classes according to the existing templates. From the results we can see that the proposed system achieves a satisfactory result.

  17. Preprotein mature domains contain translocase targeting signals that are essential for secretion.

    PubMed

    Chatzi, Katerina E; Sardis, Marios Frantzeskos; Tsirigotaki, Alexandra; Koukaki, Marina; Šoštarić, Nikolina; Konijnenberg, Albert; Sobott, Frank; Kalodimos, Charalampos G; Karamanou, Spyridoula; Economou, Anastassios

    2017-05-01

    Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as pre proteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting-competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion. © 2017 Chatzi et al.

  18. Preprotein mature domains contain translocase targeting signals that are essential for secretion

    PubMed Central

    Tsirigotaki, Alexandra; Koukaki, Marina; Šoštarić, Nikolina; Konijnenberg, Albert; Sobott, Frank; Kalodimos, Charalampos G.; Karamanou, Spyridoula

    2017-01-01

    Secretory proteins are only temporary cytoplasmic residents. They are typically synthesized as preproteins, carrying signal peptides N-terminally fused to their mature domains. In bacteria secretion largely occurs posttranslationally through the membrane-embedded SecA-SecYEG translocase. Upon crossing the plasma membrane, signal peptides are cleaved off and mature domains reach their destinations and fold. Targeting to the translocase is mediated by signal peptides. The role of mature domains in targeting and secretion is unclear. We now reveal that mature domains harbor their own independent targeting signals (mature domain targeting signals [MTSs]). These are multiple, degenerate, interchangeable, linear or 3D hydrophobic stretches that become available because of the unstructured states of targeting-competent preproteins. Their receptor site on the cytoplasmic face of the SecYEG-bound SecA is also of hydrophobic nature and is located adjacent to the signal peptide cleft. Both the preprotein MTSs and their receptor site on SecA are essential for protein secretion. Evidently, mature domains have their own previously unsuspected distinct roles in preprotein targeting and secretion. PMID:28404644

  19. Resolution of Site-Specific Conformational Heterogeneity in Proline-Rich Molecular Recognition by Src Homology 3 Domains.

    PubMed

    Horness, Rachel E; Basom, Edward J; Mayer, John P; Thielges, Megan C

    2016-02-03

    Conformational heterogeneity and dynamics are increasingly evoked in models of protein molecular recognition but are challenging to experimentally characterize. Here we combine the inherent temporal resolution of infrared (IR) spectroscopy with the spatial resolution afforded by selective incorporation of carbon-deuterium (C-D) bonds, which provide frequency-resolved absorptions within a protein IR spectrum, to characterize the molecular recognition of the Src homology 3 (SH3) domain of the yeast protein Sho1 with its cognate proline-rich (PR) sequence of Pbs2. The IR absorptions of C-D bonds introduced at residues along a peptide of the Pbs2 PR sequence report on the changes in the local environments upon binding to the SH3 domain. Interestingly, upon forming the complex the IR spectra of the peptides labeled with C-D bonds at either of the two conserved prolines of the PXXP consensus recognition sequence show more absorptions than there are C-D bonds, providing evidence for the population of multiple states. In contrast, the NMR spectra of the peptides labeled with (13)C at the same residues show only single resonances, indicating rapid interconversion on the NMR time scale. Thus, the data suggest that the SH3 domain recognizes its cognate peptide with a component of induced fit molecular recognition involving the adoption of multiples states, which have previously gone undetected due to interconversion between the populated states that is too fast to resolve using conventional methods.

  20. Using Metadynamics to Understand the Mechanism of Calmodulin/Target Recognition at Atomic Detail

    PubMed Central

    Fiorin, G.; Pastore, A.; Carloni, P.; Parrinello, M.

    2006-01-01

    The ability of calcium-bound calmodulin (CaM) to recognize most of its target peptides is caused by its binding to two hydrophobic residues (‘anchors’). In most of the CaM complexes, the anchors pack against the hydrophobic pockets of the CaM domains and are surrounded by fully conserved Met side chains. Here, by using metadynamics simulations, we investigate quantitatively the energetics of the final step of this process using the M13 peptide, which has a high affinity and spans the sequence of the skeletal myosin light chain kinase, an important natural CaM target. We established the accuracy of our calculations by a comparison between calculated and NMR-derived structural and dynamical properties. Our calculations provide novel insights into the mechanism of protein/peptide recognition: we show that the process is associated with a free energy gain similar to that experimentally measured for the CaM complex with the homologous smooth muscle MLCK peptide (Ehrhardt et al., 1995, Biochemistry 34, 2731). We suggest that binding is dominated by the entropic effect, in agreement with previous proposals. Furthermore, we explain the role of conserved methionines by showing that the large flexibility of these side chains is a key feature of the binding mechanism. Finally, we provide a rationale for the experimental observation that in all CaM complexes the C-terminal domain seems to be hierarchically more important in establishing the interaction. PMID:16877506

  1. Generating target system specifications from a domain model using CLIPS

    NASA Technical Reports Server (NTRS)

    Sugumaran, Vijayan; Gomaa, Hassan; Kerschberg, Larry

    1991-01-01

    The quest for reuse in software engineering is still being pursued and researchers are actively investigating the domain modeling approach to software construction. There are several domain modeling efforts reported in the literature and they all agree that the components that are generated from domain modeling are more conducive to reuse. Once a domain model is created, several target systems can be generated by tailoring the domain model or by evolving the domain model and then tailoring it according to the specified requirements. This paper presents the Evolutionary Domain Life Cycle (EDLC) paradigm in which a domain model is created using multiple views, namely, aggregation hierarchy, generalization/specialization hierarchies, object communication diagrams and state transition diagrams. The architecture of the Knowledge Based Requirements Elicitation Tool (KBRET) which is used to generate target system specifications is also presented. The preliminary version of KBRET is implemented in the C Language Integrated Production System (CLIPS).

  2. Testing of a Composite Wavelet Filter to Enhance Automated Target Recognition in SONAR

    NASA Technical Reports Server (NTRS)

    Chiang, Jeffrey N.

    2011-01-01

    Automated Target Recognition (ATR) systems aim to automate target detection, recognition, and tracking. The current project applies a JPL ATR system to low resolution SONAR and camera videos taken from Unmanned Underwater Vehicles (UUVs). These SONAR images are inherently noisy and difficult to interpret, and pictures taken underwater are unreliable due to murkiness and inconsistent lighting. The ATR system breaks target recognition into three stages: 1) Videos of both SONAR and camera footage are broken into frames and preprocessed to enhance images and detect Regions of Interest (ROIs). 2) Features are extracted from these ROIs in preparation for classification. 3) ROIs are classified as true or false positives using a standard Neural Network based on the extracted features. Several preprocessing, feature extraction, and training methods are tested and discussed in this report.

  3. Tumor-targeting domains for chimeric antigen receptor T cells.

    PubMed

    Bezverbnaya, Ksenia; Mathews, Ashish; Sidhu, Jesse; Helsen, Christopher W; Bramson, Jonathan L

    2017-01-01

    Immunotherapy with chimeric antigen receptor (CAR) T cells has been advancing steadily in clinical trials. Since the ability of engineered T cells to recognize intended tumor-associated targets is crucial for the therapeutic success, antigen-binding domains play an important role in shaping T-cell responses. Single-chain antibody and T-cell receptor fragments, natural ligands, repeat proteins, combinations of the above and universal tag-specific domains have all been used in the antigen-binding moiety of chimeric receptors. Here we outline the advantages and disadvantages of different domains, discuss the concepts of affinity and specificity, and highlight the recent progress of each targeting strategy.

  4. Bioinspired Pollen-Like Hierarchical Surface for Efficient Recognition of Target Cancer Cells.

    PubMed

    Wang, Wenshuo; Yang, Gao; Cui, Haijun; Meng, Jingxin; Wang, Shutao; Jiang, Lei

    2017-08-01

    The efficient recognition and isolation of rare cancer cells holds great promise for cancer diagnosis and prognosis. In nature, pollens exploit spiky structures to realize recognition and adhesion to stigma. Herein, a bioinspired pollen-like hierarchical surface is developed by replicating the assembly of pollen grains, and efficient and specific recognition to target cancer cells is achieved. The pollen-like surface is fabricated by combining filtering-assisted assembly and soft lithography-based replication of pollen grains of wild chrysanthemum. After modification with a capture agent specific to cancer cells, the pollen-like surface enables the capture of target cancer cells with high efficiency and specificity. In addition, the pollen-like surface not only assures high viability of captured cells but also performs well in cell mixture system and at low cell density. This study represents a good example of constructing cell recognition biointerfaces inspired by pollen-stigma adhesion. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  5. Targeted induction of meiotic double-strand breaks reveals chromosomal domain-dependent regulation of Spo11 and interactions among potential sites of meiotic recombination

    PubMed Central

    Fukuda, Tomoyuki; Kugou, Kazuto; Sasanuma, Hiroyuki; Shibata, Takehiko

    2008-01-01

    Meiotic recombination is initiated by programmed DNA double-strand break (DSB) formation mediated by Spo11. DSBs occur with frequency in chromosomal regions called hot domains but are seldom seen in cold domains. To obtain insights into the determinants of the distribution of meiotic DSBs, we examined the effects of inducing targeted DSBs during yeast meiosis using a UAS-directed form of Spo11 (Gal4BD-Spo11) and a meiosis-specific endonuclease, VDE (PI-SceI). Gal4BD-Spo11 cleaved its target sequence (UAS) integrated in hot domains but rarely in cold domains. However, Gal4BD-Spo11 did bind to UAS and VDE efficiently cleaved its recognition sequence in either context, suggesting that a cold domain is not a region of inaccessible or uncleavable chromosome structure. Importantly, self-association of Spo11 occurred at UAS in a hot domain but not in a cold domain, raising the possibility that Spo11 remains in an inactive intermediate state in cold domains. Integration of UAS adjacent to known DSB hotspots allowed us to detect competitive interactions among hotspots for activation. Moreover, the presence of VDE-introduced DSB repressed proximal hotspot activity, implicating DSBs themselves in interactions among hotspots. Thus, potential sites for Spo11-mediated DSB are subject to domain-specific and local competitive regulations during and after DSB formation. PMID:18096626

  6. Conformational instability of the MARK3 UBA domain compromises ubiquitin recognition and promotes interaction with the adjacent kinase domain

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

    Murphy, James M.; Korzhnev, Dmitry M.; Ceccarelli, Derek F.

    2012-10-23

    The Par-1/MARK protein kinases play a pivotal role in establishing cellular polarity. This family of kinases contains a unique domain architecture, in which a ubiquitin-associated (UBA) domain is located C-terminal to the kinase domain. We have used a combination of x-ray crystallography and NMR dynamics experiments to understand the interaction of the human (h) MARK3 UBA domain with the adjacent kinase domain as compared with ubiquitin. The x-ray crystal structure of the linked hMARK3 kinase and UBA domains establishes that the UBA domain forms a stable intramolecular interaction with the N-terminal lobe of the kinase domain. However, solution-state NMR studiesmore » of the isolated UBA domain indicate that it is highly dynamic, undergoing conformational transitions that can be explained by a folding-unfolding equilibrium. NMR titration experiments indicated that the hMARK3 UBA domain has a detectable but extremely weak affinity for mono ubiquitin, which suggests that conformational instability of the isolated hMARK3 UBA domain attenuates binding to ubiquitin despite the presence of residues typically involved in ubiquitin recognition. Our data identify a molecular mechanism through which the hMARK3 UBA domain has evolved to bind the kinase domain, in a fashion that stabilizes an open conformation of the N- and C-terminal lobes, at the expense of its capacity to engage ubiquitin. These results may be relevant more generally to the 30% of UBA domains that lack significant ubiquitin-binding activity, and they suggest a unique mechanism by which interaction domains may evolve new binding properties.« less

  7. Developmental change and cross-domain links in vocal and musical emotion recognition performance in childhood.

    PubMed

    Allgood, Rebecca; Heaton, Pamela

    2015-09-01

    Although the configurations of psychoacoustic cues signalling emotions in human vocalizations and instrumental music are very similar, cross-domain links in recognition performance have yet to be studied developmentally. Two hundred and twenty 5- to 10-year-old children were asked to identify musical excerpts and vocalizations as happy, sad, or fearful. The results revealed age-related increases in overall recognition performance with significant correlations across vocal and musical conditions at all developmental stages. Recognition scores were greater for musical than vocal stimuli and were superior in females compared with males. These results confirm that recognition of emotions in vocal and musical stimuli is linked by 5 years and that sensitivity to emotions in auditory stimuli is influenced by age and gender. © 2015 The British Psychological Society.

  8. Temporal identity in axonal target layer recognition.

    PubMed

    Petrovic, Milan; Hummel, Thomas

    2008-12-11

    The segregation of axon and dendrite projections into distinct synaptic layers is a fundamental principle of nervous system organization and the structural basis for information processing in the brain. Layer-specific recognition molecules that allow projecting neurons to stabilize transient contacts and initiate synaptogenesis have been identified. However, most of the neuronal cell-surface molecules critical for layer organization are expressed broadly in the developing nervous system, raising the question of how these so-called permissive adhesion molecules support synaptic specificity. Here we show that the temporal expression dynamics of the zinc-finger protein sequoia is the major determinant of Drosophila photoreceptor connectivity into distinct synaptic layers. Neighbouring R8 and R7 photoreceptors show consecutive peaks of elevated sequoia expression, which correspond to their sequential target-layer innervation. Loss of sequoia in R7 leads to a projection switch into the R8 recipient layer, whereas a prolonged expression in R8 induces a redirection of their axons into the R7 layer. The sequoia-induced axon targeting is mediated through the ubiquitously expressed Cadherin-N cell adhesion molecule. Our data support a model in which recognition specificity during synaptic layer formation is generated through a temporally restricted axonal competence to respond to broadly expressed adhesion molecules. Because developing neurons innervating the same target area often project in a distinct, birth-order-dependent sequence, temporal identity seems to contain crucial information in generating not only cell type diversity during neuronal division but also connection diversity of projecting neurons.

  9. SAR target recognition and posture estimation using spatial pyramid pooling within CNN

    NASA Astrophysics Data System (ADS)

    Peng, Lijiang; Liu, Xiaohua; Liu, Ming; Dong, Liquan; Hui, Mei; Zhao, Yuejin

    2018-01-01

    Many convolution neural networks(CNN) architectures have been proposed to strengthen the performance on synthetic aperture radar automatic target recognition (SAR-ATR) and obtained state-of-art results on targets classification on MSTAR database, but few methods concern about the estimation of depression angle and azimuth angle of targets. To get better effect on learning representation of hierarchies of features on both 10-class target classification task and target posture estimation tasks, we propose a new CNN architecture with spatial pyramid pooling(SPP) which can build high hierarchy of features map by dividing the convolved feature maps from finer to coarser levels to aggregate local features of SAR images. Experimental results on MSTAR database show that the proposed architecture can get high recognition accuracy as 99.57% on 10-class target classification task as the most current state-of-art methods, and also get excellent performance on target posture estimation tasks which pays attention to depression angle variety and azimuth angle variety. What's more, the results inspire us the application of deep learning on SAR target posture description.

  10. Structure of the mouse galectin-4 N-terminal carbohydrate-recognition domain reveals the mechanism of oligosaccharide recognition

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

    Krejciríková, Veronika; Pachl, Petr; Fábry, Milan

    2011-11-18

    Galectin-4, a member of the tandem-repeat subfamily of galectins, participates in cell-membrane interactions and plays an important role in cell adhesion and modulation of immunity and malignity. The oligosaccharide specificity of the mouse galectin-4 carbohydrate-recognition domains (CRDs) has been reported previously. In this work, the structure and binding properties of the N-terminal domain CRD1 were further investigated and the crystal structure of CRD1 in complex with lactose was determined at 2.1 {angstrom} resolution. The lactose-binding affinity was characterized by fluorescence measurements and two lactose-binding sites were identified: a high-affinity site with a K{sub d} value in the micromolar range (K{submore » d1} = 600 {+-} 70 {mu}M) and a low-affinity site with K{sub d2} = 28 {+-} 10 mM.« less

  11. Structural Basis for Conserved Regulation and Adaptation of the Signal Recognition Particle Targeting Complex.

    PubMed

    Wild, Klemens; Bange, Gert; Motiejunas, Domantas; Kribelbauer, Judith; Hendricks, Astrid; Segnitz, Bernd; Wade, Rebecca C; Sinning, Irmgard

    2016-07-17

    The signal recognition particle (SRP) is a ribonucleoprotein complex with a key role in targeting and insertion of membrane proteins. The two SRP GTPases, SRP54 (Ffh in bacteria) and FtsY (SRα in eukaryotes), form the core of the targeting complex (TC) regulating the SRP cycle. The architecture of the TC and its stimulation by RNA has been described for the bacterial SRP system while this information is lacking for other domains of life. Here, we present the crystal structures of the GTPase heterodimers of archaeal (Sulfolobus solfataricus), eukaryotic (Homo sapiens), and chloroplast (Arabidopsis thaliana) SRP systems. The comprehensive structural comparison combined with Brownian dynamics simulations of TC formation allows for the description of the general blueprint and of specific adaptations of the quasi-symmetric heterodimer. Our work defines conserved external nucleotide-binding sites for SRP GTPase activation by RNA. Structural analyses of the GDP-bound, post-hydrolysis states reveal a conserved, magnesium-sensitive switch within the I-box. Overall, we provide a general model for SRP cycle regulation by RNA. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Bi-Spectral Method for Radar Target Recognition

    DTIC Science & Technology

    2006-12-01

    θazimuth=60° and ϕelevation=30° with HV Polarization....................................53 Figure 50 Comparison of Radar Range Profile with Actual...radar systems. A comparison of the NCTR techniques and their relative advantages and disadvantages in target recognition performance is presented. 8...32 f fR i R R c c f fi R R i R R c c A e A e A e ψ ψ π ψ ψ π ψ ψ π ψ ψ

  13. Molecular recognition features (MoRFs) in three domains of life.

    PubMed

    Yan, Jing; Dunker, A Keith; Uversky, Vladimir N; Kurgan, Lukasz

    2016-03-01

    Intrinsically disordered proteins and protein regions offer numerous advantages in the context of protein-protein interactions when compared to the structured proteins and domains. These advantages include ability to interact with multiple partners, to fold into different conformations when bound to different partners, and to undergo disorder-to-order transitions concomitant with their functional activity. Molecular recognition features (MoRFs) are widespread elements located in disordered regions that undergo disorder-to-order transition upon binding to their protein partners. We characterize abundance, composition, and functions of MoRFs and their association with the disordered regions across 868 species spread across Eukaryota, Bacteria and Archaea. We found that although disorder is substantially elevated in Eukaryota, MoRFs have similar abundance and amino acid composition across the three domains of life. The abundance of MoRFs is highly correlated with the amount of intrinsic disorder in Bacteria and Archaea but only modestly correlated in Eukaryota. Proteins with MoRFs have significantly more disorder and MoRFs are present in many disordered regions, with Eukaryota having more MoRF-free disordered regions. MoRF-containing proteins are enriched in the ribosome, nucleus, nucleolus and microtubule and are involved in translation, protein transport, protein folding, and interactions with DNAs. Our insights into the nature and function of MoRFs enhance our understanding of the mechanisms underlying the disorder-to-order transition and protein-protein recognition and interactions. The fMoRFpred method that we used to annotate MoRFs is available at http://biomine.ece.ualberta.ca/fMoRFpred/.

  14. Progress towards the development of SH2 domain inhibitors.

    PubMed

    Kraskouskaya, Dziyana; Duodu, Eugenia; Arpin, Carolynn C; Gunning, Patrick T

    2013-04-21

    Src homology 2 (SH2) domains are 100 amino acid modular units, which recognize and bind to tyrosyl-phosphorylated peptide sequences on their target proteins, and thereby mediate intracellular protein-protein interactions. This review summarizes the progress towards the development of synthetic agents that disrupt the function of the SH2 domains in different proteins as well as the clinical relevance of targeting a specific SH2 domain. Since 1986, SH2 domains have been identified in over 110 human proteins, including kinases, transcription factors, and adaptor proteins. A number of these proteins are over-activated in many diseases, including cancer, and their function is highly dependent on their SH2 domain. Thus, inhibition of a protein's function through disrupting that of its SH2 domain has emerged as a promising approach towards the development of novel therapeutic modalities. Although targeting the SH2 domain is a challenging task in molecular recognition, the progress reported here demonstrates the feasibility of such an approach.

  15. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold*

    PubMed Central

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn; Agacan, Mark; Tempel, Wolfram; Tong, Yufeng; Nedyalkova, Lyudmila; Park, Hee-Won; Leslie, Nicholas R.; van Aalten, Daan M. F.; Downes, C. Peter; Batty, Ian H.

    2012-01-01

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105–107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those of the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules. PMID:22493426

  16. IQGAP Proteins Reveal an Atypical Phosphoinositide (aPI) Binding Domain with a Pseudo C2 Domain Fold

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

    Dixon, Miles J.; Gray, Alexander; Schenning, Martijn

    2012-10-16

    Class I phosphoinositide (PI) 3-kinases act through effector proteins whose 3-PI selectivity is mediated by a limited repertoire of structurally defined, lipid recognition domains. We describe here the lipid preferences and crystal structure of a new class of PI binding modules exemplified by select IQGAPs (IQ motif containing GTPase-activating proteins) known to coordinate cellular signaling events and cytoskeletal dynamics. This module is defined by a C-terminal 105-107 amino acid region of which IQGAP1 and -2, but not IQGAP3, binds preferentially to phosphatidylinositol 3,4,5-trisphosphate (PtdInsP3). The binding affinity for PtdInsP3, together with other, secondary target-recognition characteristics, are comparable with those ofmore » the pleckstrin homology domain of cytohesin-3 (general receptor for phosphoinositides 1), an established PtdInsP3 effector protein. Importantly, the IQGAP1 C-terminal domain and the cytohesin-3 pleckstrin homology domain, each tagged with enhanced green fluorescent protein, were both re-localized from the cytosol to the cell periphery following the activation of PI 3-kinase in Swiss 3T3 fibroblasts, consistent with their common, selective recognition of endogenous 3-PI(s). The crystal structure of the C-terminal IQGAP2 PI binding module reveals unexpected topological similarity to an integral fold of C2 domains, including a putative basic binding pocket. We propose that this module integrates select IQGAP proteins with PI 3-kinase signaling and constitutes a novel, atypical phosphoinositide binding domain that may represent the first of a larger group, each perhaps structurally unique but collectively dissimilar from the known PI recognition modules.« less

  17. Selective Targeting of SH2 Domain-Phosphotyrosine Interactions of Src Family Tyrosine Kinases with Monobodies.

    PubMed

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

    2017-05-05

    The binding of Src-homology 2 (SH2) domains to phosphotyrosine (pY) sites is critical for the autoinhibition and substrate recognition of the eight Src family kinases (SFKs). The high sequence conservation of the 120 human SH2 domains poses a significant challenge to selectively perturb the interactions of even the SFK SH2 family against the rest of the SH2 domains. We have developed synthetic binding proteins, termed monobodies, for six of the SFK SH2 domains with nanomolar affinity. Most of these monobodies competed with pY ligand binding and showed strong selectivity for either the SrcA (Yes, Src, Fyn, Fgr) or SrcB subgroup (Lck, Lyn, Blk, Hck). Interactome analysis of intracellularly expressed monobodies revealed that they bind SFKs but no other SH2-containing proteins. Three crystal structures of monobody-SH2 complexes unveiled different and only partly overlapping binding modes, which rationalized the observed selectivity and enabled structure-based mutagenesis to modulate inhibition mode and selectivity. In line with the critical roles of SFK SH2 domains in kinase autoinhibition and T-cell receptor signaling, monobodies binding the Src and Hck SH2 domains selectively activated respective recombinant kinases, whereas an Lck SH2-binding monobody inhibited proximal signaling events downstream of the T-cell receptor complex. Our results show that SFK SH2 domains can be targeted with unprecedented potency and selectivity using monobodies. They are excellent tools for dissecting SFK functions in normal development and signaling and to interfere with aberrant SFK signaling networks in cancer cells. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  18. Pharmacologic suppression of target cell recognition by engineered T cells expressing chimeric T-cell receptors.

    PubMed

    Alvarez-Vallina, L; Yañez, R; Blanco, B; Gil, M; Russell, S J

    2000-04-01

    Adoptive therapy with autologous T cells expressing chimeric T-cell receptors (chTCRs) is of potential interest for the treatment of malignancy. To limit possible T-cell-mediated damage to normal tissues that weakly express the targeted tumor antigen (Ag), we have tested a strategy for the suppression of target cell recognition by engineered T cells. Jurkat T cells were transduced with an anti-hapten chTCR tinder the control of a tetracycline-suppressible promoter and were shown to respond to Ag-positive (hapten-coated) but not to Ag-negative target cells. The engineered T cells were then reacted with hapten-coated target cells at different effector to target cell ratios before and after exposure to tetracycline. When the engineered T cells were treated with tetracycline, expression of the chTCR was greatly decreased and recognition of the hapten-coated target cells was completely suppressed. Tetracycline-mediated suppression of target cell recognition by engineered T cells may be a useful strategy to limit the toxicity of the approach to cancer gene therapy.

  19. Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold

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

    Checco, James W.; Kreitler, Dale F.; Thomas, Nicole C.

    Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. In this paper, we describe a strategy for designing oligomers containing both α- and β-amino acid residues (“α/β-peptides”) that mimic several peptides derived from the three-helix bundle “Z-domain” scaffold. We show that α/β-peptides derived from a Z-domain peptide targeting vascular endothelial growth factor (VEGF) can structurally and functionally mimic the binding surface of the parent peptide while exhibiting significantly decreased susceptibility to proteolysis. The tightest VEGF-binding α/β-peptide inhibits the VEGF 165-induced proliferation of human umbilical vein endothelialmore » cells. We demonstrate the versatility of this strategy by showing how principles underlying VEGF signaling inhibitors can be rapidly extended to produce Z-domain–mimetic α/β-peptides that bind to two other protein partners, IgG and tumor necrosis factor-α. Because well-established selection techniques can identify high-affinity Z-domain derivatives from large DNA-encoded libraries, our findings should enable the design of biostable α/β-peptides that bind tightly and specifically to diverse targets of biomedical interest. Finally, such reagents would be useful for diagnostic and therapeutic applications.« less

  20. Targeting diverse protein–protein interaction interfaces with α/β-peptides derived from the Z-domain scaffold

    DOE PAGES

    Checco, James W.; Kreitler, Dale F.; Thomas, Nicole C.; ...

    2015-03-30

    Peptide-based agents derived from well-defined scaffolds offer an alternative to antibodies for selective and high-affinity recognition of large and topologically complex protein surfaces. In this paper, we describe a strategy for designing oligomers containing both α- and β-amino acid residues (“α/β-peptides”) that mimic several peptides derived from the three-helix bundle “Z-domain” scaffold. We show that α/β-peptides derived from a Z-domain peptide targeting vascular endothelial growth factor (VEGF) can structurally and functionally mimic the binding surface of the parent peptide while exhibiting significantly decreased susceptibility to proteolysis. The tightest VEGF-binding α/β-peptide inhibits the VEGF 165-induced proliferation of human umbilical vein endothelialmore » cells. We demonstrate the versatility of this strategy by showing how principles underlying VEGF signaling inhibitors can be rapidly extended to produce Z-domain–mimetic α/β-peptides that bind to two other protein partners, IgG and tumor necrosis factor-α. Because well-established selection techniques can identify high-affinity Z-domain derivatives from large DNA-encoded libraries, our findings should enable the design of biostable α/β-peptides that bind tightly and specifically to diverse targets of biomedical interest. Finally, such reagents would be useful for diagnostic and therapeutic applications.« less

  1. 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.

  2. Information-based approach to performance estimation and requirements allocation in multisensor fusion for target recognition

    NASA Astrophysics Data System (ADS)

    Harney, Robert C.

    1997-03-01

    A novel methodology offering the potential for resolving two of the significant problems of implementing multisensor target recognition systems, i.e., the rational selection of a specific sensor suite and optimal allocation of requirements among sensors, is presented. Based on a sequence of conjectures (and their supporting arguments) concerning the relationship of extractable information content to recognition performance of a sensor system, a set of heuristics (essentially a reformulation of Johnson's criteria applicable to all sensor and data types) is developed. An approach to quantifying the information content of sensor data is described. Coupling this approach with the widely accepted Johnson's criteria for target recognition capabilities results in a quantitative method for comparing the target recognition ability of diverse sensors (imagers, nonimagers, active, passive, electromagnetic, acoustic, etc.). Extension to describing the performance of multiple sensors is straightforward. The application of the technique to sensor selection and requirements allocation is discussed.

  3. Kinetic recognition of the retinoblastoma tumor suppressor by a specific protein target.

    PubMed

    Chemes, Lucía B; Sánchez, Ignacio E; de Prat-Gay, Gonzalo

    2011-09-16

    The retinoblastoma tumor suppressor (Rb) plays a key role in cell cycle control and is linked to various types of human cancer. Rb binds to the LxCxE motif, present in a number of cellular and viral proteins such as AdE1A, SV40 large T-antigen and human papillomavirus (HPV) E7, all instrumental in revealing fundamental mechanisms of tumor suppression, cell cycle control and gene expression. A detailed kinetic study of RbAB binding to the HPV E7 oncoprotein shows that an LxCxE-containing E7 fragment binds through a fast two-state reaction strongly favored by electrostatic interactions. Conversely, full-length E7 binds through a multistep process involving a pre-equilibrium between E7 conformers, a fast electrostatically driven association step guided by the LxCxE motif and a slow conformational rearrangement. This kinetic complexity arises from the conformational plasticity and intrinsically disordered nature of E7 and from multiple interaction surfaces present in both proteins. Affinity differences between E7N domains from high- and low-risk types are explained by their dissociation rates. In fact, since Rb is at the center of a large protein interaction network, fast and tight recognition provides an advantage for disruption by the viral proteins, where the balance of physiological and pathological interactions is dictated by kinetic ligand competition. The localization of the LxCxE motif within an intrinsically disordered domain provides the fast, diffusion-controlled interaction that allows viral proteins to outcompete physiological targets. We describe the interaction mechanism of Rb with a protein ligand, at the same time an LxCxE-containing model target, and a paradigmatic intrinsically disordered viral oncoprotein. Copyright © 2011 Elsevier Ltd. All rights reserved.

  4. Knowledge-based approach for generating target system specifications from a domain model

    NASA Technical Reports Server (NTRS)

    Gomaa, Hassan; Kerschberg, Larry; Sugumaran, Vijayan

    1992-01-01

    Several institutions in industry and academia are pursuing research efforts in domain modeling to address unresolved issues in software reuse. To demonstrate the concepts of domain modeling and software reuse, a prototype software engineering environment is being developed at George Mason University to support the creation of domain models and the generation of target system specifications. This prototype environment, which is application domain independent, consists of an integrated set of commercial off-the-shelf software tools and custom-developed software tools. This paper describes the knowledge-based tool that was developed as part of the environment to generate target system specifications from a domain model.

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

    NASA Astrophysics Data System (ADS)

    Hortos, William S.

    2008-04-01

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

  6. Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes.

    PubMed

    Richardson, Carolyn C; McLaughlin, Kerry A; Morgan, Diana; Feltbower, Richard G; Christie, Michael R

    2016-02-01

    Insulinoma-associated protein 2 (IA-2) is a major target of autoimmunity in type 1 diabetes. When first detected, IA-2-autoantibodies commonly bind epitopes in the juxtamembrane (JM) domain of IA-2 and antibody responses subsequently spread to the tyrosine phosphatase domain. Definition of structures of epitopes in the JM domain, and genetic requirements for autoimmunity to these epitopes, is important for our understanding of initiation and progression of autoimmunity. The aims of this study were to investigate the contribution of individual amino acids in the IA-2 JM domain to antibody binding to these epitopes and the role of HLA genotypes in determining epitope specificity. Regions of the JM domain recognised by autoantibodies were identified by peptide competition and inhibitory effects of alanine substitutions of residues within the JM region. Antibody binding was determined by radioligand binding assays using sera from patients genotyped for HLA-DRB1 and -DQB1 alleles. Patients were categorised into two distinct groups of JM antibody reactivity according to peptide inhibition. Inhibition by substitutions of individual amino acids within the JM domain differed between patients, indicating heterogeneity in epitope recognition. Cluster analysis defined six groups of residues having similar inhibitory effects on antibody binding, with three clusters showing differences in patients affected or unaffected by peptide. One cluster demonstrated significant differences in antibody binding between HLA-DRB1*04 and HLA-DRB1*07 patients and within DRB1*04 individuals; antibody recognition of a second cluster depended on expression of HLA-DQB1*0302. The results identify amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity.

  7. TALE-PvuII fusion proteins--novel tools for gene targeting.

    PubMed

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity.

  8. Discovery of cancer drug targets by CRISPR-Cas9 screening of protein domains.

    PubMed

    Shi, Junwei; Wang, Eric; Milazzo, Joseph P; Wang, Zihua; Kinney, Justin B; Vakoc, Christopher R

    2015-06-01

    CRISPR-Cas9 genome editing technology holds great promise for discovering therapeutic targets in cancer and other diseases. Current screening strategies target CRISPR-Cas9-induced mutations to the 5' exons of candidate genes, but this approach often produces in-frame variants that retain functionality, which can obscure even strong genetic dependencies. Here we overcome this limitation by targeting CRISPR-Cas9 mutagenesis to exons encoding functional protein domains. This generates a higher proportion of null mutations and substantially increases the potency of negative selection. We also show that the magnitude of negative selection can be used to infer the functional importance of individual protein domains of interest. A screen of 192 chromatin regulatory domains in murine acute myeloid leukemia cells identifies six known drug targets and 19 additional dependencies. A broader application of this approach may allow comprehensive identification of protein domains that sustain cancer cells and are suitable for drug targeting.

  9. The striking similarities between standard, distractor-free, and target-free recognition

    PubMed Central

    Dobbins, Ian G.

    2012-01-01

    It is often assumed that observers seek to maximize correct responding during recognition testing by actively adjusting a decision criterion. However, early research by Wallace (Journal of Experimental Psychology: Human Learning and Memory 4:441–452, 1978) suggested that recognition rates for studied items remained similar, regardless of whether or not the tests contained distractor items. We extended these findings across three experiments, addressing whether detection rates or observer confidence changed when participants were presented standard tests (targets and distractors) versus “pure-list” tests (lists composed entirely of targets or distractors). Even when observers were made aware of the composition of the pure-list test, the endorsement rates and confidence patterns remained largely similar to those observed during standard testing, suggesting that observers are typically not striving to maximize the likelihood of success across the test. We discuss the implications for decision models that assume a likelihood ratio versus a strength decision axis, as well as the implications for prior findings demonstrating large criterion shifts using target probability manipulations. PMID:21476108

  10. N-terminal domain of the dual-targeted pea glutathione reductase signal peptide controls organellar targeting efficiency.

    PubMed

    Rudhe, Charlotta; Clifton, Rachel; Whelan, James; Glaser, Elzbieta

    2002-12-06

    Import of nuclear-encoded proteins into mitochondria and chloroplasts is generally organelle specific and its specificity depends on the N-terminal signal peptide. Yet, a group of proteins known as dual-targeted proteins have a targeting peptide capable of leading the mature protein to both organelles. We have investigated the domain structure of the dual-targeted pea glutathione reductase (GR) signal peptide by using N-terminal truncations. A mutant of the GR precursor (pGR) starting with the second methionine residue of the targeting peptide, pGRdelta2-4, directed import into both organelles, negating the possibility that dual import was controlled by the nature of the N terminus. The deletion of the 30 N-terminal residues (pGRdelta2-30) inhibited import efficiency into chloroplasts substantially and almost completely into mitochondria, whereas the removal of only 16 N-terminal amino acid residues (pGRdelta2-16) resulted in the strongly stimulated mitochondrial import without significantly affecting chloroplast import. Furthermore, N-terminal truncations of the signal peptide (pGRdelta2-16 and pGRdelta2-30) greatly stimulated the mitochondrial processing activity measured with the isolated processing peptidase. These results suggest a domain structure for the dual-targeting peptide of pGR and the existence of domains controlling organellar import efficiency therein.

  11. Inferring protein domains associated with drug side effects based on drug-target interaction network.

    PubMed

    Iwata, Hiroaki; Mizutani, Sayaka; Tabei, Yasuo; Kotera, Masaaki; Goto, Susumu; Yamanishi, Yoshihiro

    2013-01-01

    Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains.

  12. Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3.

    PubMed

    Diehl, Carl; Engström, Olof; Delaine, Tamara; Håkansson, Maria; Genheden, Samuel; Modig, Kristofer; Leffler, Hakon; Ryde, Ulf; Nilsson, Ulf J; Akke, Mikael

    2010-10-20

    Rational drug design is predicated on knowledge of the three-dimensional structure of the protein-ligand complex and the thermodynamics of ligand binding. Despite the fundamental importance of both enthalpy and entropy in driving ligand binding, the role of conformational entropy is rarely addressed in drug design. In this work, we have probed the conformational entropy and its relative contribution to the free energy of ligand binding to the carbohydrate recognition domain of galectin-3. Using a combination of NMR spectroscopy, isothermal titration calorimetry, and X-ray crystallography, we characterized the binding of three ligands with dissociation constants ranging over 2 orders of magnitude. (15)N and (2)H spin relaxation measurements showed that the protein backbone and side chains respond to ligand binding by increased conformational fluctuations, on average, that differ among the three ligand-bound states. Variability in the response to ligand binding is prominent in the hydrophobic core, where a distal cluster of methyl groups becomes more rigid, whereas methyl groups closer to the binding site become more flexible. The results reveal an intricate interplay between structure and conformational fluctuations in the different complexes that fine-tunes the affinity. The estimated change in conformational entropy is comparable in magnitude to the binding enthalpy, demonstrating that it contributes favorably and significantly to ligand binding. We speculate that the relatively weak inherent protein-carbohydrate interactions and limited hydrophobic effect associated with oligosaccharide binding might have exerted evolutionary pressure on carbohydrate-binding proteins to increase the affinity by means of conformational entropy.

  13. Structural and sequencing analysis of local target DNA recognition by MLV integrase.

    PubMed

    Aiyer, Sriram; Rossi, Paolo; Malani, Nirav; Schneider, William M; Chandar, Ashwin; Bushman, Frederic D; Montelione, Gaetano T; Roth, Monica J

    2015-06-23

    Target-site selection by retroviral integrase (IN) proteins profoundly affects viral pathogenesis. We describe the solution nuclear magnetic resonance structure of the Moloney murine leukemia virus IN (M-MLV) C-terminal domain (CTD) and a structural homology model of the catalytic core domain (CCD). In solution, the isolated MLV IN CTD adopts an SH3 domain fold flanked by a C-terminal unstructured tail. We generated a concordant MLV IN CCD structural model using SWISS-MODEL, MMM-tree and I-TASSER. Using the X-ray crystal structure of the prototype foamy virus IN target capture complex together with our MLV domain structures, residues within the CCD α2 helical region and the CTD β1-β2 loop were predicted to bind target DNA. The role of these residues was analyzed in vivo through point mutants and motif interchanges. Viable viruses with substitutions at the IN CCD α2 helical region and the CTD β1-β2 loop were tested for effects on integration target site selection. Next-generation sequencing and analysis of integration target sequences indicate that the CCD α2 helical region, in particular P187, interacts with the sequences distal to the scissile bonds whereas the CTD β1-β2 loop binds to residues proximal to it. These findings validate our structural model and disclose IN-DNA interactions relevant to target site selection. © The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.

  14. Unsupervised Spatial Event Detection in Targeted Domains with Applications to Civil Unrest Modeling

    PubMed Central

    Zhao, Liang; Chen, Feng; Dai, Jing; Hua, Ting; Lu, Chang-Tien; Ramakrishnan, Naren

    2014-01-01

    Twitter has become a popular data source as a surrogate for monitoring and detecting events. Targeted domains such as crime, election, and social unrest require the creation of algorithms capable of detecting events pertinent to these domains. Due to the unstructured language, short-length messages, dynamics, and heterogeneity typical of Twitter data streams, it is technically difficult and labor-intensive to develop and maintain supervised learning systems. We present a novel unsupervised approach for detecting spatial events in targeted domains and illustrate this approach using one specific domain, viz. civil unrest modeling. Given a targeted domain, we propose a dynamic query expansion algorithm to iteratively expand domain-related terms, and generate a tweet homogeneous graph. An anomaly identification method is utilized to detect spatial events over this graph by jointly maximizing local modularity and spatial scan statistics. Extensive experiments conducted in 10 Latin American countries demonstrate the effectiveness of the proposed approach. PMID:25350136

  15. Automated Target Acquisition, Recognition and Tracking (ATTRACT). Phase 1

    NASA Technical Reports Server (NTRS)

    Abdallah, Mahmoud A.

    1995-01-01

    The primary objective of phase 1 of this research project is to conduct multidisciplinary research that will contribute to fundamental scientific knowledge in several of the USAF critical technology areas. Specifically, neural networks, signal processing techniques, and electro-optic capabilities are utilized to solve problems associated with automated target acquisition, recognition, and tracking. To accomplish the stated objective, several tasks have been identified and were executed.

  16. Morphological self-organizing feature map neural network with applications to automatic target recognition

    NASA Astrophysics Data System (ADS)

    Zhang, Shijun; Jing, Zhongliang; Li, Jianxun

    2005-01-01

    The rotation invariant feature of the target is obtained using the multi-direction feature extraction property of the steerable filter. Combining the morphological operation top-hat transform with the self-organizing feature map neural network, the adaptive topological region is selected. Using the erosion operation, the topological region shrinkage is achieved. The steerable filter based morphological self-organizing feature map neural network is applied to automatic target recognition of binary standard patterns and real-world infrared sequence images. Compared with Hamming network and morphological shared-weight networks respectively, the higher recognition correct rate, robust adaptability, quick training, and better generalization of the proposed method are achieved.

  17. Structural requirements of oleosin domains for subcellular targeting to the oil body.

    PubMed Central

    van Rooijen, G J; Moloney, M M

    1995-01-01

    We have investigated the protein domains responsible for the correct subcellular targeting of plant seed oleosins. We have attempted to study this targeting in vivo using "tagged" oleosins in transgenic plants. Different constructs were prepared lacking gene sequences encoding one of three structural domains of natural oleosins. Each was fused in frame to the Escherichia coli uid A gene encoding beta-glucuronidase (GUS). These constructs were introduced into Brassica napus using Agrobacterium-mediated transformation. GUS activity was measured in washed oil bodies and in the soluble protein fraction of the transgenic seeds. It was found that complete Arabidopsis oleosin-GUS fusions undergo correct subcellular targeting in transgenic Brassica seeds. Removal of the C-terminal domain of the Arabidopsis oleosin comprising the last 48 amino acids had no effect on overall subcellular targeting. In contrast, loss of the first 47 amino acids (N terminus) or amino acids 48 to 113 (which make up a lipophilic core) resulted in impaired targeting of the fusion protein to the oil bodies and greatly reduced accumulation of the fusion protein. Northern blotting revealed that this reduction is not due to differences in mRNA accumulation. Results from these measurements indicated that both the N-terminal and central oleosin domain are important for targeting to the oil body and show that there is a direct correlation between the inability to target to the oil body and protein stability. PMID:8539295

  18. A hierarchical, automated target recognition algorithm for a parallel analog processor

    NASA Technical Reports Server (NTRS)

    Woodward, Gail; Padgett, Curtis

    1997-01-01

    A hierarchical approach is described for an automated target recognition (ATR) system, VIGILANTE, that uses a massively parallel, analog processor (3DANN). The 3DANN processor is capable of performing 64 concurrent inner products of size 1x4096 every 250 nanoseconds.

  19. TALE-PvuII Fusion Proteins – Novel Tools for Gene Targeting

    PubMed Central

    Yanik, Mert; Alzubi, Jamal; Lahaye, Thomas; Cathomen, Toni; Pingoud, Alfred; Wende, Wolfgang

    2013-01-01

    Zinc finger nucleases (ZFNs) consist of zinc fingers as DNA-binding module and the non-specific DNA-cleavage domain of the restriction endonuclease FokI as DNA-cleavage module. This architecture is also used by TALE nucleases (TALENs), in which the DNA-binding modules of the ZFNs have been replaced by DNA-binding domains based on transcription activator like effector (TALE) proteins. Both TALENs and ZFNs are programmable nucleases which rely on the dimerization of FokI to induce double-strand DNA cleavage at the target site after recognition of the target DNA by the respective DNA-binding module. TALENs seem to have an advantage over ZFNs, as the assembly of TALE proteins is easier than that of ZFNs. Here, we present evidence that variant TALENs can be produced by replacing the catalytic domain of FokI with the restriction endonuclease PvuII. These fusion proteins recognize only the composite recognition site consisting of the target site of the TALE protein and the PvuII recognition sequence (addressed site), but not isolated TALE or PvuII recognition sites (unaddressed sites), even at high excess of protein over DNA and long incubation times. In vitro, their preference for an addressed over an unaddressed site is > 34,000-fold. Moreover, TALE-PvuII fusion proteins are active in cellula with minimal cytotoxicity. PMID:24349308

  20. Inferring protein domains associated with drug side effects based on drug-target interaction network

    PubMed Central

    2013-01-01

    Background Most phenotypic effects of drugs are involved in the interactions between drugs and their target proteins, however, our knowledge about the molecular mechanism of the drug-target interactions is very limited. One of challenging issues in recent pharmaceutical science is to identify the underlying molecular features which govern drug-target interactions. Results In this paper, we make a systematic analysis of the correlation between drug side effects and protein domains, which we call "pharmacogenomic features," based on the drug-target interaction network. We detect drug side effects and protein domains that appear jointly in known drug-target interactions, which is made possible by using classifiers with sparse models. It is shown that the inferred pharmacogenomic features can be used for predicting potential drug-target interactions. We also discuss advantages and limitations of the pharmacogenomic features, compared with the chemogenomic features that are the associations between drug chemical substructures and protein domains. Conclusion The inferred side effect-domain association network is expected to be useful for estimating common drug side effects for different protein families and characteristic drug side effects for specific protein domains. PMID:24565527

  1. Convolutional neural networks based on augmented training samples for synthetic aperture radar target recognition

    NASA Astrophysics Data System (ADS)

    Yan, Yue

    2018-03-01

    A synthetic aperture radar (SAR) automatic target recognition (ATR) method based on the convolutional neural networks (CNN) trained by augmented training samples is proposed. To enhance the robustness of CNN to various extended operating conditions (EOCs), the original training images are used to generate the noisy samples at different signal-to-noise ratios (SNRs), multiresolution representations, and partially occluded images. Then, the generated images together with the original ones are used to train a designed CNN for target recognition. The augmented training samples can contrapuntally improve the robustness of the trained CNN to the covered EOCs, i.e., the noise corruption, resolution variance, and partial occlusion. Moreover, the significantly larger training set effectively enhances the representation capability for other conditions, e.g., the standard operating condition (SOC), as well as the stability of the network. Therefore, better performance can be achieved by the proposed method for SAR ATR. For experimental evaluation, extensive experiments are conducted on the Moving and Stationary Target Acquisition and Recognition dataset under SOC and several typical EOCs.

  2. Target-context unitization effect on the familiarity-related FN400: a face recognition exclusion task.

    PubMed

    Guillaume, Fabrice; Etienne, Yann

    2015-03-01

    Using two exclusion tasks, the present study examined how the ERP correlates of face recognition are affected by the nature of the information to be retrieved. Intrinsic (facial expression) and extrinsic (background scene) visual information were paired with face identity and constituted the exclusion criterion at test time. Although perceptual information had to be taken into account in both situations, the FN400 old-new effect was observed only for old target faces on the expression-exclusion task, whereas it was found for both old target and old non-target faces in the background-exclusion situation. These results reveal that the FN400, which is generally interpreted as a correlate of familiarity, was modulated by the retrieval of intra-item and intrinsic face information, but not by the retrieval of extrinsic information. The observed effects on the FN400 depended on the nature of the information to be retrieved and its relationship (unitization) to the recognition target. On the other hand, the parietal old-new effect (generally described as an ERP correlate of recollection) reflected the retrieval of both types of contextual features equivalently. The current findings are discussed in relation to recent controversies about the nature of the recognition processes reflected by the ERP correlates of face recognition. Copyright © 2015 Elsevier B.V. All rights reserved.

  3. Structural Insights Into the Recognition of Peroxisomal Targeting Signal 1 By Trypanosoma Brucei Peroxin 5

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

    Sampathkumar, P.; Roach, C.; Michels, P.A.M.

    2009-05-27

    Glycosomes are peroxisome-like organelles essential for trypanosomatid parasites. Glycosome biogenesis is mediated by proteins called 'peroxins,' which are considered to be promising drug targets in pathogenic Trypanosomatidae. The first step during protein translocation across the glycosomal membrane of peroxisomal targeting signal 1 (PTS1)-harboring proteins is signal recognition by the cytosolic receptor peroxin 5 (PEX5). The C-terminal PTS1 motifs interact with the PTS1 binding domain (P1BD) of PEX5, which is made up of seven tetratricopeptide repeats. Obtaining diffraction-quality crystals of the P1BD of Trypanosoma brucei PEX5 (TbPEX5) required surface entropy reduction mutagenesis. Each of the seven tetratricopeptide repeats appears to havemore » a residue in the alpha(L) conformation in the loop connecting helices A and B. Five crystal structures of the P1BD of TbPEX5 were determined, each in complex with a hepta- or decapeptide corresponding to a natural or nonnatural PTS1 sequence. The PTS1 peptides are bound between the two subdomains of the P1BD. These structures indicate precise recognition of the C-terminal Leu of the PTS1 motif and important interactions between the PTS1 peptide main chain and up to five invariant Asn side chains of PEX5. The TbPEX5 structures reported here reveal a unique hydrophobic pocket in the subdomain interface that might be explored to obtain compounds that prevent relative motions of the subdomains and interfere selectively with PTS1 motif binding or release in trypanosomatids, and would therefore disrupt glycosome biogenesis and prevent parasite growth.« less

  4. Learning target masks in infrared linescan imagery

    NASA Astrophysics Data System (ADS)

    Fechner, Thomas; Rockinger, Oliver; Vogler, Axel; Knappe, Peter

    1997-04-01

    In this paper we propose a neural network based method for the automatic detection of ground targets in airborne infrared linescan imagery. Instead of using a dedicated feature extraction stage followed by a classification procedure, we propose the following three step scheme: In the first step of the recognition process, the input image is decomposed into its pyramid representation, thus obtaining a multiresolution signal representation. At the lowest three levels of the Laplacian pyramid a neural network filter of moderate size is trained to indicate the target location. The last step consists of a fusion process of the several neural network filters to obtain the final result. To perform this fusion we use a belief network to combine the various filter outputs in a statistical meaningful way. In addition, the belief network allows the integration of further knowledge about the image domain. By applying this multiresolution recognition scheme, we obtain a nearly scale- and rotational invariant target recognition with a significantly decreased false alarm rate compared with a single resolution target recognition scheme.

  5. Thermodynamics of DNA target site recognition by homing endonucleases

    PubMed Central

    Eastberg, Jennifer H.; Smith, Audrey McConnell; Zhao, Lei; Ashworth, Justin; Shen, Betty W.; Stoddard, Barry L.

    2007-01-01

    The thermodynamic profiles of target site recognition have been surveyed for homing endonucleases from various structural families. Similar to DNA-binding proteins that recognize shorter target sites, homing endonucleases display a narrow range of binding free energies and affinities, mediated by structural interactions that balance the magnitude of enthalpic and entropic forces. While the balance of ΔH and TΔS are not strongly correlated with the overall extent of DNA bending, unfavorable ΔHbinding is associated with unstacking of individual base steps in the target site. The effects of deleterious basepair substitutions in the optimal target sites of two LAGLIDADG homing endonucleases, and the subsequent effect of redesigning one of those endonucleases to accommodate that DNA sequence change, were also measured. The substitution of base-specific hydrogen bonds in a wild-type endonuclease/DNA complex with hydrophobic van der Waals contacts in a redesigned complex reduced the ability to discriminate between sites, due to nonspecific ΔSbinding. PMID:17947319

  6. Superdiffusive motion of membrane-targeting C2 domains

    NASA Astrophysics Data System (ADS)

    Campagnola, Grace; Nepal, Kanti; Schroder, Bryce W.; Peersen, Olve B.; Krapf, Diego

    2015-12-01

    Membrane-targeting domains play crucial roles in the recruitment of signalling molecules to the plasma membrane. For most peripheral proteins, the protein-to-membrane interaction is transient. After proteins dissociate from the membrane they have been observed to rebind following brief excursions in the bulk solution. Such membrane hops can have broad implications for the efficiency of reactions on membranes. We study the diffusion of membrane-targeting C2 domains using single-molecule tracking in supported lipid bilayers. The ensemble-averaged mean square displacement (MSD) exhibits superdiffusive behaviour. However, traditional time-averaged MSD analysis of individual trajectories remains linear and does not reveal superdiffusion. Our observations are explained in terms of bulk excursions that introduce jumps with a heavy-tail distribution. These hopping events allow proteins to explore large areas in a short time. The experimental results are shown to be consistent with analytical models of bulk-mediated diffusion and numerical simulations.

  7. Using llama derived single domain antibodies to target botulinum neurotoxins

    NASA Astrophysics Data System (ADS)

    Swain, Marla D.; Anderson, George P.; Bernstein, Rachael D.; Liu, Jinny L.; Goldman, Ellen R.

    2010-04-01

    Llama serum contains both conventional IgG as well as unique forms of antibody that contain only heavy chains where antigen binding is mediated through a single variable domain. These variable domains can be expressed recombinantly and are referred to as single domain antibodies (sdAb). SdAb are among the smallest known naturally derived antigen binding fragments, possess good solubility, thermal stability, and can refold after heat and chemical denaturation. Llamas were immunized with either BoNT A or B toxoid and phage display libraries prepared. Single domain antibodies (sdAb) that were able to detect botulinum neurotoxin (BoNT) serotypes A and B were selected from their respective libraries. Here, the binders obtained by panning the BoNT B library on either BoNT B toxoid or BoNT B complex toxoid coated plates or BoNT B toxin coupled microspheres are described. Using these panning methods, we selected for binders that showed specificity for BoNT B. Phage displayed binders were screened, moved to a protein expression vector and soluble sdAb was produced. Using a Luminex flow cytometer binders were evaluated in direct binding assays. We have exploited the unique properties of sdAb and used them as biological recognition elements in immuno-based sensors that can detect BoNT B.

  8. DNA recognition by an RNA-guided bacterial Argonaute

    PubMed Central

    Doudna, Jennifer A.

    2017-01-01

    Argonaute (Ago) proteins are widespread in prokaryotes and eukaryotes and share a four-domain architecture capable of RNA- or DNA-guided nucleic acid recognition. Previous studies identified a prokaryotic Argonaute protein from the eubacterium Marinitoga piezophila (MpAgo), which binds preferentially to 5′-hydroxylated guide RNAs and cleaves single-stranded RNA (ssRNA) and DNA (ssDNA) targets. Here we present a 3.2 Å resolution crystal structure of MpAgo bound to a 21-nucleotide RNA guide and a complementary 21-nucleotide ssDNA substrate. Comparison of this ternary complex to other target-bound Argonaute structures reveals a unique orientation of the N-terminal domain, resulting in a straight helical axis of the entire RNA-DNA heteroduplex through the central cleft of the protein. Additionally, mismatches introduced into the heteroduplex reduce MpAgo cleavage efficiency with a symmetric profile centered around the middle of the helix. This pattern differs from the canonical mismatch tolerance of other Argonautes, which display decreased cleavage efficiency for substrates bearing sequence mismatches to the 5′ region of the guide strand. This structural analysis of MpAgo bound to a hybrid helix advances our understanding of the diversity of target recognition mechanisms by Argonaute proteins. PMID:28520746

  9. Deep Learning Methods for Underwater Target Feature Extraction and Recognition

    PubMed Central

    Peng, Yuan; Qiu, Mengran; Shi, Jianfei; Liu, Liangliang

    2018-01-01

    The classification and recognition technology of underwater acoustic signal were always an important research content in the field of underwater acoustic signal processing. Currently, wavelet transform, Hilbert-Huang transform, and Mel frequency cepstral coefficients are used as a method of underwater acoustic signal feature extraction. In this paper, a method for feature extraction and identification of underwater noise data based on CNN and ELM is proposed. An automatic feature extraction method of underwater acoustic signals is proposed using depth convolution network. An underwater target recognition classifier is based on extreme learning machine. Although convolution neural networks can execute both feature extraction and classification, their function mainly relies on a full connection layer, which is trained by gradient descent-based; the generalization ability is limited and suboptimal, so an extreme learning machine (ELM) was used in classification stage. Firstly, CNN learns deep and robust features, followed by the removing of the fully connected layers. Then ELM fed with the CNN features is used as the classifier to conduct an excellent classification. Experiments on the actual data set of civil ships obtained 93.04% recognition rate; compared to the traditional Mel frequency cepstral coefficients and Hilbert-Huang feature, recognition rate greatly improved. PMID:29780407

  10. Integrated approach for automatic target recognition using a network of collaborative sensors.

    PubMed

    Mahalanobis, Abhijit; Van Nevel, Alan

    2006-10-01

    We introduce what is believed to be a novel concept by which several sensors with automatic target recognition (ATR) capability collaborate to recognize objects. Such an approach would be suitable for netted systems in which the sensors and platforms can coordinate to optimize end-to-end performance. We use correlation filtering techniques to facilitate the development of the concept, although other ATR algorithms may be easily substituted. Essentially, a self-configuring geometry of netted platforms is proposed that positions the sensors optimally with respect to each other, and takes into account the interactions among the sensor, the recognition algorithms, and the classes of the objects to be recognized. We show how such a paradigm optimizes overall performance, and illustrate the collaborative ATR scheme for recognizing targets in synthetic aperture radar imagery by using viewing position as a sensor parameter.

  11. Research and Development of Target Recognition and Location Crawling Platform based on Binocular Vision

    NASA Astrophysics Data System (ADS)

    Xu, Weidong; Lei, Zhu; Yuan, Zhang; Gao, Zhenqing

    2018-03-01

    The application of visual recognition technology in industrial robot crawling and placing operation is one of the key tasks in the field of robot research. In order to improve the efficiency and intelligence of the material sorting in the production line, especially to realize the sorting of the scattered items, the robot target recognition and positioning crawling platform based on binocular vision is researched and developed. The images were collected by binocular camera, and the images were pretreated. Harris operator was used to identify the corners of the images. The Canny operator was used to identify the images. Hough-chain code recognition was used to identify the images. The target image in the image, obtain the coordinates of each vertex of the image, calculate the spatial position and posture of the target item, and determine the information needed to capture the movement and transmit it to the robot control crawling operation. Finally, In this paper, we use this method to experiment the wrapping problem in the express sorting process The experimental results show that the platform can effectively solve the problem of sorting of loose parts, so as to achieve the purpose of efficient and intelligent sorting.

  12. Modes of Interaction of Pleckstrin Homology Domains with Membranes: Toward a Computational Biochemistry of Membrane Recognition.

    PubMed

    Naughton, Fiona B; Kalli, Antreas C; Sansom, Mark S P

    2018-02-02

    Pleckstrin homology (PH) domains mediate protein-membrane interactions by binding to phosphatidylinositol phosphate (PIP) molecules. The structural and energetic basis of selective PH-PIP interactions is central to understanding many cellular processes, yet the molecular complexities of the PH-PIP interactions are largely unknown. Molecular dynamics simulations using a coarse-grained model enables estimation of free-energy landscapes for the interactions of 12 different PH domains with membranes containing PIP 2 or PIP 3 , allowing us to obtain a detailed molecular energetic understanding of the complexities of the interactions of the PH domains with PIP molecules in membranes. Distinct binding modes, corresponding to different distributions of cationic residues on the PH domain, were observed, involving PIP interactions at either the "canonical" (C) and/or "alternate" (A) sites. PH domains can be grouped by the relative strength of their C- and A-site interactions, revealing that a higher affinity correlates with increased C-site interactions. These simulations demonstrate that simultaneous binding of multiple PIP molecules by PH domains contributes to high-affinity membrane interactions, informing our understanding of membrane recognition by PH domains in vivo. Copyright © 2017. Published by Elsevier Ltd.

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

    NASA Technical Reports Server (NTRS)

    Tescher, Andrew G. (Editor)

    1989-01-01

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

  14. Analysis of the Protein Domain and Domain Architecture Content in Fungi and Its Application in the Search of New Antifungal Targets

    PubMed Central

    Barrera, Alejandro; Alastruey-Izquierdo, Ana; Martín, María J.; Cuesta, Isabel; Vizcaíno, Juan Antonio

    2014-01-01

    Over the past several years fungal infections have shown an increasing incidence in the susceptible population, and caused high mortality rates. In parallel, multi-resistant fungi are emerging in human infections. Therefore, the identification of new potential antifungal targets is a priority. The first task of this study was to analyse the protein domain and domain architecture content of the 137 fungal proteomes (corresponding to 111 species) available in UniProtKB (UniProt KnowledgeBase) by January 2013. The resulting list of core and exclusive domain and domain architectures is provided in this paper. It delineates the different levels of fungal taxonomic classification: phylum, subphylum, order, genus and species. The analysis highlighted Aspergillus as the most diverse genus in terms of exclusive domain content. In addition, we also investigated which domains could be considered promiscuous in the different organisms. As an application of this analysis, we explored three different ways to detect potential targets for antifungal drugs. First, we compared the domain and domain architecture content of the human and fungal proteomes, and identified those domains and domain architectures only present in fungi. Secondly, we looked for information regarding fungal pathways in public repositories, where proteins containing promiscuous domains could be involved. Three pathways were identified as a result: lovastatin biosynthesis, xylan degradation and biosynthesis of siroheme. Finally, we classified a subset of the studied fungi in five groups depending on their occurrence in clinical samples. We then looked for exclusive domains in the groups that were more relevant clinically and determined which of them had the potential to bind small molecules. Overall, this study provides a comprehensive analysis of the available fungal proteomes and shows three approaches that can be used as a first step in the detection of new antifungal targets. PMID:25033262

  15. Analysis of the protein domain and domain architecture content in fungi and its application in the search of new antifungal targets.

    PubMed

    Barrera, Alejandro; Alastruey-Izquierdo, Ana; Martín, María J; Cuesta, Isabel; Vizcaíno, Juan Antonio

    2014-07-01

    Over the past several years fungal infections have shown an increasing incidence in the susceptible population, and caused high mortality rates. In parallel, multi-resistant fungi are emerging in human infections. Therefore, the identification of new potential antifungal targets is a priority. The first task of this study was to analyse the protein domain and domain architecture content of the 137 fungal proteomes (corresponding to 111 species) available in UniProtKB (UniProt KnowledgeBase) by January 2013. The resulting list of core and exclusive domain and domain architectures is provided in this paper. It delineates the different levels of fungal taxonomic classification: phylum, subphylum, order, genus and species. The analysis highlighted Aspergillus as the most diverse genus in terms of exclusive domain content. In addition, we also investigated which domains could be considered promiscuous in the different organisms. As an application of this analysis, we explored three different ways to detect potential targets for antifungal drugs. First, we compared the domain and domain architecture content of the human and fungal proteomes, and identified those domains and domain architectures only present in fungi. Secondly, we looked for information regarding fungal pathways in public repositories, where proteins containing promiscuous domains could be involved. Three pathways were identified as a result: lovastatin biosynthesis, xylan degradation and biosynthesis of siroheme. Finally, we classified a subset of the studied fungi in five groups depending on their occurrence in clinical samples. We then looked for exclusive domains in the groups that were more relevant clinically and determined which of them had the potential to bind small molecules. Overall, this study provides a comprehensive analysis of the available fungal proteomes and shows three approaches that can be used as a first step in the detection of new antifungal targets.

  16. Directed evolution of the TALE N-terminal domain for recognition of all 5' bases.

    PubMed

    Lamb, Brian M; Mercer, Andrew C; Barbas, Carlos F

    2013-11-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5'-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5' T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5' T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes.

  17. An intermolecular binding mechanism involving multiple LysM domains mediates carbohydrate recognition by an endopeptidase

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

    Wong, Jaslyn E. M. M.; Midtgaard, Søren Roi; Gysel, Kira

    The crystal and solution structures of the T. thermophilus NlpC/P60 d, l-endopeptidase as well as the co-crystal structure of its N-terminal LysM domains bound to chitohexaose allow a proposal to be made regarding how the enzyme recognizes peptidoglycan. LysM domains, which are frequently present as repetitive entities in both bacterial and plant proteins, are known to interact with carbohydrates containing N-acetylglucosamine (GlcNAc) moieties, such as chitin and peptidoglycan. In bacteria, the functional significance of the involvement of multiple LysM domains in substrate binding has so far lacked support from high-resolution structures of ligand-bound complexes. Here, a structural study of themore » Thermus thermophilus NlpC/P60 endopeptidase containing two LysM domains is presented. The crystal structure and small-angle X-ray scattering solution studies of this endopeptidase revealed the presence of a homodimer. The structure of the two LysM domains co-crystallized with N-acetyl-chitohexaose revealed a new intermolecular binding mode that may explain the differential interaction between LysM domains and short or long chitin oligomers. By combining the structural information with the three-dimensional model of peptidoglycan, a model suggesting how protein dimerization enhances the recognition of peptidoglycan is proposed.« less

  18. Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity.

    PubMed

    Chong, P Andrew; Lin, Hong; Wrana, Jeffrey L; Forman-Kay, Julie D

    2010-10-26

    Smad ubiquitination regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that participates in degradation of TGF-β receptors and other targets. Smurf2 WW domains recognize PPXY (PY) motifs on ubiquitin ligase target proteins or on adapters, such as Smad7, that bind to E3 target proteins. We previously demonstrated that the isolated WW3 domain of Smurf2, but not the WW2 domain, can directly bind to a Smad7 PY motif. We show here that the WW2 augments this interaction by binding to the WW3 and making auxiliary contacts with the PY motif and a novel E/D-S/T-P motif, which is N-terminal to all Smad PY motifs. The WW2 likely enhances the selectivity of Smurf2 for the Smad proteins. NMR titrations confirm that Smad1 and Smad2 are bound by Smurf2 with the same coupled WW domain arrangement used to bind Smad7. The analogous WW domains in the short isoform of Smurf1 recognize the Smad7 PY peptide using the same coupled mechanism. However, a longer Smurf1 isoform, which has an additional 26 residues in the inter-WW domain linker, is only partially able to use the coupled WW domain binding mechanism. The longer linker results in a decrease in affinity for the Smad7 peptide. Interdomain coupling of WW domains enhances selectivity and enables the tuning of interactions by isoform switching.

  19. Coupling of tandem Smad ubiquitination regulatory factor (Smurf) WW domains modulates target specificity

    PubMed Central

    Chong, P. Andrew; Lin, Hong; Wrana, Jeffrey L.; Forman-Kay, Julie D.

    2010-01-01

    Smad ubiquitination regulatory factor 2 (Smurf2) is an E3 ubiquitin ligase that participates in degradation of TGF-β receptors and other targets. Smurf2 WW domains recognize PPXY (PY) motifs on ubiquitin ligase target proteins or on adapters, such as Smad7, that bind to E3 target proteins. We previously demonstrated that the isolated WW3 domain of Smurf2, but not the WW2 domain, can directly bind to a Smad7 PY motif. We show here that the WW2 augments this interaction by binding to the WW3 and making auxiliary contacts with the PY motif and a novel E/D-S/T-P motif, which is N-terminal to all Smad PY motifs. The WW2 likely enhances the selectivity of Smurf2 for the Smad proteins. NMR titrations confirm that Smad1 and Smad2 are bound by Smurf2 with the same coupled WW domain arrangement used to bind Smad7. The analogous WW domains in the short isoform of Smurf1 recognize the Smad7 PY peptide using the same coupled mechanism. However, a longer Smurf1 isoform, which has an additional 26 residues in the inter-WW domain linker, is only partially able to use the coupled WW domain binding mechanism. The longer linker results in a decrease in affinity for the Smad7 peptide. Interdomain coupling of WW domains enhances selectivity and enables the tuning of interactions by isoform switching. PMID:20937913

  20. Infrared images target detection based on background modeling in the discrete cosine domain

    NASA Astrophysics Data System (ADS)

    Ye, Han; Pei, Jihong

    2018-02-01

    Background modeling is the critical technology to detect the moving target for video surveillance. Most background modeling techniques are aimed at land monitoring and operated in the spatial domain. A background establishment becomes difficult when the scene is a complex fluctuating sea surface. In this paper, the background stability and separability between target are analyzed deeply in the discrete cosine transform (DCT) domain, on this basis, we propose a background modeling method. The proposed method models each frequency point as a single Gaussian model to represent background, and the target is extracted by suppressing the background coefficients. Experimental results show that our approach can establish an accurate background model for seawater, and the detection results outperform other background modeling methods in the spatial domain.

  1. Low, slow, small target recognition based on spatial vision network

    NASA Astrophysics Data System (ADS)

    Cheng, Zhao; Guo, Pei; Qi, Xin

    2018-03-01

    Traditional photoelectric monitoring is monitored using a large number of identical cameras. In order to ensure the full coverage of the monitoring area, this monitoring method uses more cameras, which leads to more monitoring and repetition areas, and higher costs, resulting in more waste. In order to reduce the monitoring cost and solve the difficult problem of finding, identifying and tracking a low altitude, slow speed and small target, this paper presents spatial vision network for low-slow-small targets recognition. Based on camera imaging principle and monitoring model, spatial vision network is modeled and optimized. Simulation experiment results demonstrate that the proposed method has good performance.

  2. Competitive Deep-Belief Networks for Underwater Acoustic Target Recognition

    PubMed Central

    Shen, Sheng; Yao, Xiaohui; Sheng, Meiping; Wang, Chen

    2018-01-01

    Underwater acoustic target recognition based on ship-radiated noise belongs to the small-sample-size recognition problems. A competitive deep-belief network is proposed to learn features with more discriminative information from labeled and unlabeled samples. The proposed model consists of four stages: (1) A standard restricted Boltzmann machine is pretrained using a large number of unlabeled data to initialize its parameters; (2) the hidden units are grouped according to categories, which provides an initial clustering model for competitive learning; (3) competitive training and back-propagation algorithms are used to update the parameters to accomplish the task of clustering; (4) by applying layer-wise training and supervised fine-tuning, a deep neural network is built to obtain features. Experimental results show that the proposed method can achieve classification accuracy of 90.89%, which is 8.95% higher than the accuracy obtained by the compared methods. In addition, the highest accuracy of our method is obtained with fewer features than other methods. PMID:29570642

  3. Evaluation of target acquisition difficulty using recognition distance to measure required retinal area

    NASA Astrophysics Data System (ADS)

    Nilsson, Thomy H.

    2001-09-01

    The psychophysical method of limits was used to measure the distance at which observers could distinguish military vehicles photographed in natural landscapes. Obtained from the TNO-TM Search_2 dataset, these pictures either were rear-projected 35-mm slides or were presented on a computer monitor. Based on the rationale that more difficult vehicle targets would require more visual pathways for recognition, difficult of acquisition was defined in terms of the relative retinal area required for recognition. Relative retinal area was derived from the inverse square of the recognition distance of a particular vehicle relative to the distance of the vehicle that could be seen furthest away. Results are compared with data on the time required to find the vehicles in these pictures. These comparison indicate recognition distance thresholds can be a suitable means of defining standards for the effectiveness of vital graphic information; and the two methods are complementary with respect to distinguishing different degrees of acquisition difficulty, and together may provide a means to measure the total information processing required for recognition.

  4. Structures of the Signal Recognition Particle Receptor from the Archaeon Pyrococcus furiosus: Implications for the Targeting Step at the Membrane

    PubMed Central

    Egea, Pascal F.; Tsuruta, Hiro; de Leon, Gladys P.; Napetschnig, Johanna; Walter, Peter; Stroud, Robert M.

    2008-01-01

    In all organisms, a ribonucleoprotein called the signal recognition particle (SRP) and its receptor (SR) target nascent proteins from the ribosome to the translocon for secretion or membrane insertion. We present the first X-ray structures of an archeal FtsY, the receptor from the hyper-thermophile Pyrococcus furiosus (Pfu), in its free and GDP•magnesium-bound forms. The highly charged N-terminal domain of Pfu-FtsY is distinguished by a long N-terminal helix. The basic charges on the surface of this helix are likely to regulate interactions at the membrane. A peripheral GDP bound near a regulatory motif could indicate a site of interaction between the receptor and ribosomal or SRP RNAs. Small angle X-ray scattering and analytical ultracentrifugation indicate that the crystal structure of Pfu-FtsY correlates well with the average conformation in solution. Based on previous structures of two sub-complexes, we propose a model of the core of archeal and eukaryotic SRP•SR targeting complexes. PMID:18978942

  5. Infrared target simulation environment for pattern recognition applications

    NASA Astrophysics Data System (ADS)

    Savakis, Andreas E.; George, Nicholas

    1994-07-01

    The generation of complete databases of IR data is extremely useful for training human observers and testing automatic pattern recognition algorithms. Field data may be used for realism, but require expensive and time-consuming procedures. IR scene simulation methods have emerged as a more economical and efficient alternative for the generation of IR databases. A novel approach to IR target simulation is presented in this paper. Model vehicles at 1:24 scale are used for the simulation of real targets. The temperature profile of the model vehicles is controlled using resistive circuits which are embedded inside the models. The IR target is recorded using an Inframetrics dual channel IR camera system. Using computer processing we place the recorded IR target in a prerecorded background. The advantages of this approach are: (1) the range and 3D target aspect can be controlled by the relative position between the camera and model vehicle; (2) the temperature profile can be controlled by adjusting the power delivered to the resistive circuit; (3) the IR sensor effects are directly incorporated in the recording process, because the real sensor is used; (4) the recorded target can embedded in various types of backgrounds recorded under different weather conditions, times of day etc. The effectiveness of this approach is demonstrated by generating an IR database of three vehicles which is used to train a back propagation neural network. The neural network is capable of classifying vehicle type, vehicle aspect, and relative temperature with a high degree of accuracy.

  6. Cooperative interactions between paired domain and homeodomain.

    PubMed

    Jun, S; Desplan, C

    1996-09-01

    The Pax proteins are a family of transcriptional regulators involved in many developmental processes in all higher eukaryotes. They are characterized by the presence of a paired domain (PD), a bipartite DNA binding domain composed of two helix-turn-helix (HTH) motifs,the PAI and RED domains. The PD is also often associated with a homeodomain (HD) which is itself able to form homo- and hetero-dimers on DNA. Many of these proteins therefore contain three HTH motifs each able to recognize DNA. However, all PDs recognize highly related DNA sequences, and most HDs also recognize almost identical sites. We show here that different Pax proteins use multiple combinations of their HTHs to recognize several types of target sites. For instance, the Drosophila Paired protein can bind, in vitro, exclusively through its PAI domain, or through a dimer of its HD, or through cooperative interaction between PAI domain and HD. However, prd function in vivo requires the synergistic action of both the PAI domain and the HD. Pax proteins with only a PD appear to require both PAI and RED domains, while a Pax-6 isoform and a new Pax protein, Lune, may rely on the RED domain and HD. We propose a model by which Pax proteins recognize different target genes in vivo through various combinations of their DNA binding domains, thus expanding their recognition repertoire.

  7. MicroRNAs: Processing, Maturation, Target Recognition and Regulatory Functions

    PubMed Central

    Shukla, Girish C.; Singh, Jagjit; Barik, Sailen

    2012-01-01

    The remarkable discovery of small noncoding microRNAs (miRNAs) and their role in posttranscriptional gene regulation have revealed another fine-tuning step in the expression of genetic information. A large number of cellular pathways, which act in organismal development and are important in health and disease, appear to be modulated by miRNAs. At the molecular level, miRNAs restrain the production of proteins by affecting the stability of their target mRNA and/or by down-regulating their translation. This review attempts to offer a snapshot of aspects of miRNA coding, processing, target recognition and function in animals. Our goal here is to provide the readers with a thought-provoking and mechanistic introduction to the miRNA world rather than with a detailed encyclopedia. PMID:22468167

  8. Characterization of the molecular basis of group II intron RNA recognition by CRS1-CRM domains.

    PubMed

    Keren, Ido; Klipcan, Liron; Bezawork-Geleta, Ayenachew; Kolton, Max; Shaya, Felix; Ostersetzer-Biran, Oren

    2008-08-22

    CRM (chloroplast RNA splicing and ribosome maturation) is a recently recognized RNA-binding domain of ancient origin that has been retained in eukaryotic genomes only within the plant lineage. Whereas in bacteria CRM domains exist as single domain proteins involved in ribosome maturation, in plants they are found in a family of proteins that contain between one and four repeats. Several members of this family with multiple CRM domains have been shown to be required for the splicing of specific plastidic group II introns. Detailed biochemical analysis of one of these factors in maize, CRS1, demonstrated its high affinity and specific binding to the single group II intron whose splicing it facilitates, the plastid-encoded atpF intron RNA. Through its association with two intronic regions, CRS1 guides the folding of atpF intron RNA into its predicted "catalytically active" form. To understand how multiple CRM domains cooperate to achieve high affinity sequence-specific binding to RNA, we analyzed the RNA binding affinity and specificity associated with each individual CRM domain in CRS1; whereas CRM3 bound tightly to the RNA, CRM1 associated specifically with a unique region found within atpF intron domain I. CRM2, which demonstrated only low binding affinity, also seems to form specific interactions with regions localized to domains I, III, and IV. We further show that CRM domains share structural similarities and RNA binding characteristics with the well known RNA recognition motif domain.

  9. Artificial neural networks for acoustic target recognition

    NASA Astrophysics Data System (ADS)

    Robertson, James A.; Mossing, John C.; Weber, Bruce A.

    1995-04-01

    Acoustic sensors can be used to detect, track and identify non-line-of-sight targets passively. Attempts to alter acoustic emissions often result in an undesirable performance degradation. This research project investigates the use of neural networks for differentiating between features extracted from the acoustic signatures of sources. Acoustic data were filtered and digitized using a commercially available analog-digital convertor. The digital data was transformed to the frequency domain for additional processing using the FFT. Narrowband peak detection algorithms were incorporated to select peaks above a user defined SNR. These peaks were then used to generate a set of robust features which relate specifically to target components in varying background conditions. The features were then used as input into a backpropagation neural network. A K-means unsupervised clustering algorithm was used to determine the natural clustering of the observations. Comparisons between a feature set consisting of the normalized amplitudes of the first 250 frequency bins of the power spectrum and a set of 11 harmonically related features were made. Initial results indicate that even though some different target types had a tendency to group in the same clusters, the neural network was able to differentiate the targets. Successful identification of acoustic sources under varying operational conditions with high confidence levels was achieved.

  10. Recognition mechanism of p63 by the E3 ligase Itch

    PubMed Central

    Bellomaria, Alessia; Barbato, Gaetano; Melino, Gerry; Paci, Maurizio; Melino, Sonia

    2012-01-01

    The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer’s or Huntington’s diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly ¹³C-¹⁵N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534–551 residue of p63, encompassing the PPxY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PPxY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase. PMID:22935697

  11. Feature extraction and selection strategies for automated target recognition

    NASA Astrophysics Data System (ADS)

    Greene, W. Nicholas; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

    2010-04-01

    Several feature extraction and selection methods for an existing automatic target recognition (ATR) system using JPLs Grayscale Optical Correlator (GOC) and Optimal Trade-Off Maximum Average Correlation Height (OT-MACH) filter were tested using MATLAB. The ATR system is composed of three stages: a cursory regionof- interest (ROI) search using the GOC and OT-MACH filter, a feature extraction and selection stage, and a final classification stage. Feature extraction and selection concerns transforming potential target data into more useful forms as well as selecting important subsets of that data which may aide in detection and classification. The strategies tested were built around two popular extraction methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). Performance was measured based on the classification accuracy and free-response receiver operating characteristic (FROC) output of a support vector machine(SVM) and a neural net (NN) classifier.

  12. A fast recognition method of warhead target in boost phase using kinematic features

    NASA Astrophysics Data System (ADS)

    Chen, Jian; Xu, Shiyou; Tian, Biao; Wu, Jianhua; Chen, Zengping

    2015-12-01

    The radar targets number increases from one to more when the ballistic missile is in the process of separating the lower stage rocket or casting covers or other components. It is vital to identify the warhead target quickly among these multiple targets for radar tracking. A fast recognition method of the warhead target is proposed to solve this problem by using kinematic features, utilizing fuzzy comprehensive method and information fusion method. In order to weaken the influence of radar measurement noise, an extended Kalman filter with constant jerk model (CJEKF) is applied to obtain more accurate target's motion information. The simulation shows the validity of the algorithm and the effects of the radar measurement precision upon the algorithm's performance.

  13. The research of edge extraction and target recognition based on inherent feature of objects

    NASA Astrophysics Data System (ADS)

    Xie, Yu-chan; Lin, Yu-chi; Huang, Yin-guo

    2008-03-01

    Current research on computer vision often needs specific techniques for particular problems. Little use has been made of high-level aspects of computer vision, such as three-dimensional (3D) object recognition, that are appropriate for large classes of problems and situations. In particular, high-level vision often focuses mainly on the extraction of symbolic descriptions, and pays little attention to the speed of processing. In order to extract and recognize target intelligently and rapidly, in this paper we developed a new 3D target recognition method based on inherent feature of objects in which cuboid was taken as model. On the basis of analysis cuboid nature contour and greyhound distributing characteristics, overall fuzzy evaluating technique was utilized to recognize and segment the target. Then Hough transform was used to extract and match model's main edges, we reconstruct aim edges by stereo technology in the end. There are three major contributions in this paper. Firstly, the corresponding relations between the parameters of cuboid model's straight edges lines in an image field and in the transform field were summed up. By those, the aimless computations and searches in Hough transform processing can be reduced greatly and the efficiency is improved. Secondly, as the priori knowledge about cuboids contour's geometry character known already, the intersections of the component extracted edges are taken, and assess the geometry of candidate edges matches based on the intersections, rather than the extracted edges. Therefore the outlines are enhanced and the noise is depressed. Finally, a 3-D target recognition method is proposed. Compared with other recognition methods, this new method has a quick response time and can be achieved with high-level computer vision. The method present here can be used widely in vision-guide techniques to strengthen its intelligence and generalization, which can also play an important role in object tracking, port AGV, robots

  14. EEG based topography analysis in string recognition task

    NASA Astrophysics Data System (ADS)

    Ma, Xiaofei; Huang, Xiaolin; Shen, Yuxiaotong; Qin, Zike; Ge, Yun; Chen, Ying; Ning, Xinbao

    2017-03-01

    Vision perception and recognition is a complex process, during which different parts of brain are involved depending on the specific modality of the vision target, e.g. face, character, or word. In this study, brain activities in string recognition task compared with idle control state are analyzed through topographies based on multiple measurements, i.e. sample entropy, symbolic sample entropy and normalized rhythm power, extracted from simultaneously collected scalp EEG. Our analyses show that, for most subjects, both symbolic sample entropy and normalized gamma power in string recognition task are significantly higher than those in idle state, especially at locations of P4, O2, T6 and C4. It implies that these regions are highly involved in string recognition task. Since symbolic sample entropy measures complexity, from the perspective of new information generation, and normalized rhythm power reveals the power distributions in frequency domain, complementary information about the underlying dynamics can be provided through the two types of indices.

  15. Wavelet-Based Signal and Image Processing for Target Recognition

    NASA Astrophysics Data System (ADS)

    Sherlock, Barry G.

    2002-11-01

    The PI visited NSWC Dahlgren, VA, for six weeks in May-June 2002 and collaborated with scientists in the G33 TEAMS facility, and with Marilyn Rudzinsky of T44 Technology and Photonic Systems Branch. During this visit the PI also presented six educational seminars to NSWC scientists on various aspects of signal processing. Several items from the grant proposal were completed, including (1) wavelet-based algorithms for interpolation of 1-d signals and 2-d images; (2) Discrete Wavelet Transform domain based algorithms for filtering of image data; (3) wavelet-based smoothing of image sequence data originally obtained for the CRITTIR (Clutter Rejection Involving Temporal Techniques in the Infra-Red) project. The PI visited the University of Stellenbosch, South Africa to collaborate with colleagues Prof. B.M. Herbst and Prof. J. du Preez on the use of wavelet image processing in conjunction with pattern recognition techniques. The University of Stellenbosch has offered the PI partial funding to support a sabbatical visit in Fall 2003, the primary purpose of which is to enable the PI to develop and enhance his expertise in Pattern Recognition. During the first year, the grant supported publication of 3 referred papers, presentation of 9 seminars and an intensive two-day course on wavelet theory. The grant supported the work of two students who functioned as research assistants.

  16. Automated target recognition using passive radar and coordinated flight models

    NASA Astrophysics Data System (ADS)

    Ehrman, Lisa M.; Lanterman, Aaron D.

    2003-09-01

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

  17. Target recognition of ladar range images using slice image: comparison of four improved algorithms

    NASA Astrophysics Data System (ADS)

    Xia, Wenze; Han, Shaokun; Cao, Jingya; Wang, Liang; Zhai, Yu; Cheng, Yang

    2017-07-01

    Compared with traditional 3-D shape data, ladar range images possess properties of strong noise, shape degeneracy, and sparsity, which make feature extraction and representation difficult. The slice image is an effective feature descriptor to resolve this problem. We propose four improved algorithms on target recognition of ladar range images using slice image. In order to improve resolution invariance of the slice image, mean value detection instead of maximum value detection is applied in these four improved algorithms. In order to improve rotation invariance of the slice image, three new improved feature descriptors-which are feature slice image, slice-Zernike moments, and slice-Fourier moments-are applied to the last three improved algorithms, respectively. Backpropagation neural networks are used as feature classifiers in the last two improved algorithms. The performance of these four improved recognition systems is analyzed comprehensively in the aspects of the three invariances, recognition rate, and execution time. The final experiment results show that the improvements for these four algorithms reach the desired effect, the three invariances of feature descriptors are not directly related to the final recognition performance of recognition systems, and these four improved recognition systems have different performances under different conditions.

  18. An algorithm for automatic target recognition using passive radar and an EKF for estimating aircraft orientation

    NASA Astrophysics Data System (ADS)

    Ehrman, Lisa M.

    2005-07-01

    Rather than emitting pulses, passive radar systems rely on "illuminators of opportunity," such as TV and FM radio, to illuminate potential targets. These systems are attractive since they allow receivers to operate without emitting energy, rendering them covert. Until recently, most of the research regarding passive radar has focused on detecting and tracking targets. This dissertation focuses on extending the capabilities of passive radar systems to include automatic target recognition. The target recognition algorithm described in this dissertation uses the radar cross section (RCS) of potential targets, collected over a short period of time, as the key information for target recognition. To make the simulated RCS as accurate as possible, the received signal model accounts for aircraft position and orientation, propagation losses, and antenna gain patterns. An extended Kalman filter (EKF) estimates the target's orientation (and uncertainty in the estimate) from velocity measurements obtained from the passive radar tracker. Coupling the aircraft orientation and state with the known antenna locations permits computation of the incident and observed azimuth and elevation angles. The Fast Illinois Solver Code (FISC) simulates the RCS of potential target classes as a function of these angles. Thus, the approximated incident and observed angles allow the appropriate RCS to be extracted from a database of FISC results. Using this process, the RCS of each aircraft in the target class is simulated as though each is executing the same maneuver as the target detected by the system. Two additional scaling processes are required to transform the RCS into a power profile (magnitude only) simulating the signal in the receiver. First, the RCS is scaled by the Advanced Refractive Effects Prediction System (AREPS) code to account for propagation losses that occur as functions of altitude and range. Then, the Numerical Electromagnetic Code (NEC2) computes the antenna gain pattern

  19. Face Recognition Deficits in Autism Spectrum Disorders Are Both Domain Specific and Process Specific

    PubMed Central

    Weigelt, Sarah; Koldewyn, Kami; Kanwisher, Nancy

    2013-01-01

    Although many studies have reported face identity recognition deficits in autism spectrum disorders (ASD), two fundamental question remains: 1) Is this deficit “process specific” for face memory in particular, or does it extend to perceptual discrimination of faces as well? And 2) Is the deficit “domain specific” for faces, or is it found more generally for other social or even nonsocial stimuli? The answers to these questions are important both for understanding the nature of autism and its developmental etiology, and for understanding the functional architecture of face processing in the typical brain. Here we show that children with ASD are impaired (compared to age and IQ-matched typical children) in face memory, but not face perception, demonstrating process specificity. Further, we find no deficit for either memory or perception of places or cars, indicating domain specificity. Importantly, we further showed deficits in both the perception and memory of bodies, suggesting that the relevant domain of deficit may be social rather than specifically facial. These results provide a more precise characterization of the cognitive phenotype of autism and further indicate a functional dissociation between face memory and face perception. PMID:24040276

  20. Specific intermolecular interactions of conserved water molecules with amino acids in the Galectin-1 carbohydrate recognition domain

    NASA Astrophysics Data System (ADS)

    Di Lella, Santiago; Petruk, Ariel A.; Armiño, Diego J. Alonso de; Álvarez, Rosa M. S.

    2010-08-01

    Water molecules, rigidly associated to protein surfaces, play a key role in stabilizing biomolecules and participating in their biological functions. Recent studies on the solvation properties of the carbohydrate recognition domain of Galectin-1 by means of molecular dynamic simulations have revealed the existence of several water sites which were well correlated to both the bound water molecules observed in the crystal structure of the protein in the free state and to some of the hydroxyl groups of the carbohydrate ligand observed in the crystal structure of the complexed protein. In this work, we present a study using quantum mechanical methods (B3LYP/6-311++G(3df,3dp)//B3LYP/6-31+G(d)) to determine the energy involved in the binding of these water molecules to specific amino acids in the carbohydrate recognition domain of the protein. By modeling the hydroxyl groups of the carbohydrate by methanol, the energies associated to the local interactions between the ligand and the protein have been evaluated by replacing specific water molecules with methanol. The values of the binding energies have been compared to those previously obtained by the molecular dynamic method.

  1. Sub-Domains of Ricin’s B Subunit as Targets of Toxin Neutralizing and Non-Neutralizing Monoclonal Antibodies

    PubMed Central

    Yermakova, Anastasiya; Vance, David J.; Mantis, Nicholas J.

    2012-01-01

    The B subunit (RTB) of ricin toxin is a galactose (Gal)−/N-acetylgalactosamine (GalNac)-specific lectin that mediates attachment, entry, and intracellular trafficking of ricin in host cells. Structurally, RTB consists of two globular domains with identical folding topologies. Domains 1 and 2 are each comprised of three homologous sub-domains (α, β, γ) that likely arose by gene duplication from a primordial carbohydrate recognition domain (CRD), although only sub-domains 1α and 2γ retain functional lectin activity. As part of our ongoing effort to generate a comprehensive B cell epitope map of ricin, we report the characterization of three new RTB-specific monoclonal antibodies (mAbs). All three mAbs, JB4, B/J F9 and C/M A2, were initially identified based on their abilities to neutralize ricin in a Vero cell cytotoxicty assay and to partially (or completely) block ricin attachment to cell surfaces. However, only JB4 proved capable of neutralizing ricin in a macrophage apoptosis assay and in imparting passive immunity to mice in a model of systemic intoxication. Using a combination of techniques, including competitive ELISAs, pepscan analysis, differential reactivity by Western blot, as well as affinity enrichment of phage displayed peptides, we tentatively localized the epitopes recognized by the non-neutralizing mAbs B/J F9 and C/M A2 to sub-domains 2α and 2β, respectively. Furthermore, we propose that the epitope recognized by JB4 is within sub-domain 2γ, adjacent to RTB’s high affinity Gal/GalNAc CRD. These data suggest that recognition of RTB’s sub-domains 1α and 2γ are critical determinants of antibody neutralizing activity and protective immunity to ricin. PMID:22984492

  2. Ubiquitin-like domains can target to the proteasome but proteolysis requires a disordered region.

    PubMed

    Yu, Houqing; Kago, Grace; Yellman, Christopher M; Matouschek, Andreas

    2016-07-15

    Ubiquitin and some of its homologues target proteins to the proteasome for degradation. Other ubiquitin-like domains are involved in cellular processes unrelated to the proteasome, and proteins containing these domains remain stable in the cell. We find that the 10 yeast ubiquitin-like domains tested bind to the proteasome, and that all 11 identified domains can target proteins for degradation. Their apparent proteasome affinities are not directly related to their stabilities or functions. That is, ubiquitin-like domains in proteins not part of the ubiquitin proteasome system may bind the proteasome more tightly than domains in proteins that are bona fide components. We propose that proteins with ubiquitin-like domains have properties other than proteasome binding that confer stability. We show that one of these properties is the absence of accessible disordered regions that allow the proteasome to initiate degradation. In support of this model, we find that Mdy2 is degraded in yeast when a disordered region in the protein becomes exposed and that the attachment of a disordered region to Ubp6 leads to its degradation. © 2016 The Authors.

  3. Feature Extraction and Selection Strategies for Automated Target Recognition

    NASA Technical Reports Server (NTRS)

    Greene, W. Nicholas; Zhang, Yuhan; Lu, Thomas T.; Chao, Tien-Hsin

    2010-01-01

    Several feature extraction and selection methods for an existing automatic target recognition (ATR) system using JPLs Grayscale Optical Correlator (GOC) and Optimal Trade-Off Maximum Average Correlation Height (OT-MACH) filter were tested using MATLAB. The ATR system is composed of three stages: a cursory region of-interest (ROI) search using the GOC and OT-MACH filter, a feature extraction and selection stage, and a final classification stage. Feature extraction and selection concerns transforming potential target data into more useful forms as well as selecting important subsets of that data which may aide in detection and classification. The strategies tested were built around two popular extraction methods: Principal Component Analysis (PCA) and Independent Component Analysis (ICA). Performance was measured based on the classification accuracy and free-response receiver operating characteristic (FROC) output of a support vector machine(SVM) and a neural net (NN) classifier.

  4. Directed evolution of the TALE N-terminal domain for recognition of all 5′ bases

    PubMed Central

    Lamb, Brian M.; Mercer, Andrew C.; Barbas, Carlos F.

    2013-01-01

    Transcription activator-like effector (TALE) proteins can be designed to bind virtually any DNA sequence. General guidelines for design of TALE DNA-binding domains suggest that the 5′-most base of the DNA sequence bound by the TALE (the N0 base) should be a thymine. We quantified the N0 requirement by analysis of the activities of TALE transcription factors (TALE-TF), TALE recombinases (TALE-R) and TALE nucleases (TALENs) with each DNA base at this position. In the absence of a 5′ T, we observed decreases in TALE activity up to >1000-fold in TALE-TF activity, up to 100-fold in TALE-R activity and up to 10-fold reduction in TALEN activity compared with target sequences containing a 5′ T. To develop TALE architectures that recognize all possible N0 bases, we used structure-guided library design coupled with TALE-R activity selections to evolve novel TALE N-terminal domains to accommodate any N0 base. A G-selective domain and broadly reactive domains were isolated and characterized. The engineered TALE domains selected in the TALE-R format demonstrated modularity and were active in TALE-TF and TALEN architectures. Evolved N-terminal domains provide effective and unconstrained TALE-based targeting of any DNA sequence as TALE binding proteins and designer enzymes. PMID:23980031

  5. Structural Basis for Endosomal Targeting by the Bro1 Domain

    PubMed Central

    Kim, Jaewon; Sitaraman, Sujatha; Hierro, Aitor; Beach, Bridgette M.; Odorizzi, Greg; Hurley, James H.

    2010-01-01

    Summary Proteins delivered to the lysosome or the yeast vacuole via late endosomes are sorted by the ESCRT complexes and by associated proteins, including Alix and its yeast homolog Bro1. Alix, Bro1, and several other late endosomal proteins share a conserved 160 residue Bro1 domain whose boundaries, structure, and function have not been characterized. The crystal structure of the Bro1 domain of Bro1 reveals a folded core of 367 residues. The extended Bro1 domain is necessary and sufficient for binding to the ESCRT-III subunit Snf7 and for the recruitment of Bro1 to late endosomes. The structure resembles a boomerang with its concave face filled in and contains a triple tetratricopeptide repeat domain as a substructure. Snf7 binds to a conserved hydrophobic patch on Bro1 that is required for protein complex formation and for the protein-sorting function of Bro1. These results define a conserved mechanism whereby Bro1 domain-containing proteins are targeted to endosomes by Snf7 and its orthologs. PMID:15935782

  6. Genetic specificity of face recognition.

    PubMed

    Shakeshaft, Nicholas G; Plomin, Robert

    2015-10-13

    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities.

  7. Characterizing protein domain associations by Small-molecule ligand binding

    PubMed Central

    Li, Qingliang; Cheng, Tiejun; Wang, Yanli; Bryant, Stephen H.

    2012-01-01

    Background Protein domains are evolutionarily conserved building blocks for protein structure and function, which are conventionally identified based on protein sequence or structure similarity. Small molecule binding domains are of great importance for the recognition of small molecules in biological systems and drug development. Many small molecules, including drugs, have been increasingly identified to bind to multiple targets, leading to promiscuous interactions with protein domains. Thus, a large scale characterization of the protein domains and their associations with respect to small-molecule binding is of particular interest to system biology research, drug target identification, as well as drug repurposing. Methods We compiled a collection of 13,822 physical interactions of small molecules and protein domains derived from the Protein Data Bank (PDB) structures. Based on the chemical similarity of these small molecules, we characterized pairwise associations of the protein domains and further investigated their global associations from a network point of view. Results We found that protein domains, despite lack of similarity in sequence and structure, were comprehensively associated through binding the same or similar small-molecule ligands. Moreover, we identified modules in the domain network that consisted of closely related protein domains by sharing similar biochemical mechanisms, being involved in relevant biological pathways, or being regulated by the same cognate cofactors. Conclusions A novel protein domain relationship was identified in the context of small-molecule binding, which is complementary to those identified by traditional sequence-based or structure-based approaches. The protein domain network constructed in the present study provides a novel perspective for chemogenomic study and network pharmacology, as well as target identification for drug repurposing. PMID:23745168

  8. Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment

    PubMed Central

    Iezzi, María Elena; Policastro, Lucía; Werbajh, Santiago; Podhajcer, Osvaldo; Canziani, Gabriela Alicia

    2018-01-01

    Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs), in particular those engineered from the variable heavy-chain fragment (VHH gene) found in Camelidae heavy-chain antibodies (or IgG2 and IgG3), are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs. For similar reasons, growing attention is being paid to the yet smaller variable heavy chain new antigen receptor (VNAR) fragments found in Squalidae. sdAbs have been selected, mostly from immune VHH libraries, to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This succinct review is a compilation of recent data documenting the application of engineered, recombinant sdAb in the clinic as epitope recognition “modules” to build monomeric, dimeric and multimeric ligands that target, tag and stall solid tumor growth in vivo. Size, affinity, specificity, and the development profile of sdAbs drugs are seemingly consistent with desirable clinical efficacy and safety requirements. But the hepatotoxicity of the tetrameric anti-DR5-VHH drug in patients with pre-existing anti-drug antibodies halted the phase I clinical trial and called for a thorough pre-screening of the immune and poly-specific reactivities of the sdAb leads. PMID:29520274

  9. Single-Domain Antibodies and the Promise of Modular Targeting in Cancer Imaging and Treatment.

    PubMed

    Iezzi, María Elena; Policastro, Lucía; Werbajh, Santiago; Podhajcer, Osvaldo; Canziani, Gabriela Alicia

    2018-01-01

    Monoclonal antibodies and their fragments have significantly changed the outcome of cancer in the clinic, effectively inhibiting tumor cell proliferation, triggering antibody-dependent immune effector cell activation and complement mediated cell death. Along with a continued expansion in number, diversity, and complexity of validated tumor targets there is an increasing focus on engineering recombinant antibody fragments for lead development. Single-domain antibodies (sdAbs), in particular those engineered from the variable heavy-chain fragment (VHH gene) found in Camelidae heavy-chain antibodies (or IgG2 and IgG3), are the smallest fragments that retain the full antigen-binding capacity of the antibody with advantageous properties as drugs. For similar reasons, growing attention is being paid to the yet smaller variable heavy chain new antigen receptor (VNAR) fragments found in Squalidae. sdAbs have been selected, mostly from immune VHH libraries, to inhibit or modulate enzyme activity, bind soluble factors, internalize cell membrane receptors, or block cytoplasmic targets. This succinct review is a compilation of recent data documenting the application of engineered, recombinant sdAb in the clinic as epitope recognition "modules" to build monomeric, dimeric and multimeric ligands that target, tag and stall solid tumor growth in vivo . Size, affinity, specificity, and the development profile of sdAbs drugs are seemingly consistent with desirable clinical efficacy and safety requirements. But the hepatotoxicity of the tetrameric anti-DR5-VHH drug in patients with pre-existing anti-drug antibodies halted the phase I clinical trial and called for a thorough pre-screening of the immune and poly-specific reactivities of the sdAb leads.

  10. Incorporating domain knowledge in chemical and biomedical named entity recognition with word representations.

    PubMed

    Munkhdalai, Tsendsuren; Li, Meijing; Batsuren, Khuyagbaatar; Park, Hyeon Ah; Choi, Nak Hyeon; Ryu, Keun Ho

    2015-01-01

    Chemical and biomedical Named Entity Recognition (NER) is an essential prerequisite task before effective text mining can begin for biochemical-text data. Exploiting unlabeled text data to leverage system performance has been an active and challenging research topic in text mining due to the recent growth in the amount of biomedical literature. We present a semi-supervised learning method that efficiently exploits unlabeled data in order to incorporate domain knowledge into a named entity recognition model and to leverage system performance. The proposed method includes Natural Language Processing (NLP) tasks for text preprocessing, learning word representation features from a large amount of text data for feature extraction, and conditional random fields for token classification. Other than the free text in the domain, the proposed method does not rely on any lexicon nor any dictionary in order to keep the system applicable to other NER tasks in bio-text data. We extended BANNER, a biomedical NER system, with the proposed method. This yields an integrated system that can be applied to chemical and drug NER or biomedical NER. We call our branch of the BANNER system BANNER-CHEMDNER, which is scalable over millions of documents, processing about 530 documents per minute, is configurable via XML, and can be plugged into other systems by using the BANNER Unstructured Information Management Architecture (UIMA) interface. BANNER-CHEMDNER achieved an 85.68% and an 86.47% F-measure on the testing sets of CHEMDNER Chemical Entity Mention (CEM) and Chemical Document Indexing (CDI) subtasks, respectively, and achieved an 87.04% F-measure on the official testing set of the BioCreative II gene mention task, showing remarkable performance in both chemical and biomedical NER. BANNER-CHEMDNER system is available at: https://bitbucket.org/tsendeemts/banner-chemdner.

  11. Object recognition using deep convolutional neural networks with complete transfer and partial frozen layers

    NASA Astrophysics Data System (ADS)

    Kruithof, Maarten C.; Bouma, Henri; Fischer, Noëlle M.; Schutte, Klamer

    2016-10-01

    Object recognition is important to understand the content of video and allow flexible querying in a large number of cameras, especially for security applications. Recent benchmarks show that deep convolutional neural networks are excellent approaches for object recognition. This paper describes an approach of domain transfer, where features learned from a large annotated dataset are transferred to a target domain where less annotated examples are available as is typical for the security and defense domain. Many of these networks trained on natural images appear to learn features similar to Gabor filters and color blobs in the first layer. These first-layer features appear to be generic for many datasets and tasks while the last layer is specific. In this paper, we study the effect of copying all layers and fine-tuning a variable number. We performed an experiment with a Caffe-based network on 1000 ImageNet classes that are randomly divided in two equal subgroups for the transfer from one to the other. We copy all layers and vary the number of layers that is fine-tuned and the size of the target dataset. We performed additional experiments with the Keras platform on CIFAR-10 dataset to validate general applicability. We show with both platforms and both datasets that the accuracy on the target dataset improves when more target data is used. When the target dataset is large, it is beneficial to freeze only a few layers. For a large target dataset, the network without transfer learning performs better than the transfer network, especially if many layers are frozen. When the target dataset is small, it is beneficial to transfer (and freeze) many layers. For a small target dataset, the transfer network boosts generalization and it performs much better than the network without transfer learning. Learning time can be reduced by freezing many layers in a network.

  12. The study of infrared target recognition at sea background based on visual attention computational model

    NASA Astrophysics Data System (ADS)

    Wang, Deng-wei; Zhang, Tian-xu; Shi, Wen-jun; Wei, Long-sheng; Wang, Xiao-ping; Ao, Guo-qing

    2009-07-01

    Infrared images at sea background are notorious for the low signal-to-noise ratio, therefore, the target recognition of infrared image through traditional methods is very difficult. In this paper, we present a novel target recognition method based on the integration of visual attention computational model and conventional approach (selective filtering and segmentation). The two distinct techniques for image processing are combined in a manner to utilize the strengths of both. The visual attention algorithm searches the salient regions automatically, and represented them by a set of winner points, at the same time, demonstrated the salient regions in terms of circles centered at these winner points. This provides a priori knowledge for the filtering and segmentation process. Based on the winner point, we construct a rectangular region to facilitate the filtering and segmentation, then the labeling operation will be added selectively by requirement. Making use of the labeled information, from the final segmentation result we obtain the positional information of the interested region, label the centroid on the corresponding original image, and finish the localization for the target. The cost time does not depend on the size of the image but the salient regions, therefore the consumed time is greatly reduced. The method is used in the recognition of several kinds of real infrared images, and the experimental results reveal the effectiveness of the algorithm presented in this paper.

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

    NASA Astrophysics Data System (ADS)

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

    2018-01-01

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

  14. Autonomous space target recognition and tracking approach using star sensors based on a Kalman filter.

    PubMed

    Ye, Tao; Zhou, Fuqiang

    2015-04-10

    When imaged by detectors, space targets (including satellites and debris) and background stars have similar point-spread functions, and both objects appear to change as detectors track targets. Therefore, traditional tracking methods cannot separate targets from stars and cannot directly recognize targets in 2D images. Consequently, we propose an autonomous space target recognition and tracking approach using a star sensor technique and a Kalman filter (KF). A two-step method for subpixel-scale detection of star objects (including stars and targets) is developed, and the combination of the star sensor technique and a KF is used to track targets. The experimental results show that the proposed method is adequate for autonomously recognizing and tracking space targets.

  15. Genetic specificity of face recognition

    PubMed Central

    Shakeshaft, Nicholas G.; Plomin, Robert

    2015-01-01

    Specific cognitive abilities in diverse domains are typically found to be highly heritable and substantially correlated with general cognitive ability (g), both phenotypically and genetically. Recent twin studies have found the ability to memorize and recognize faces to be an exception, being similarly heritable but phenotypically substantially uncorrelated both with g and with general object recognition. However, the genetic relationships between face recognition and other abilities (the extent to which they share a common genetic etiology) cannot be determined from phenotypic associations. In this, to our knowledge, first study of the genetic associations between face recognition and other domains, 2,000 18- and 19-year-old United Kingdom twins completed tests assessing their face recognition, object recognition, and general cognitive abilities. Results confirmed the substantial heritability of face recognition (61%), and multivariate genetic analyses found that most of this genetic influence is unique and not shared with other cognitive abilities. PMID:26417086

  16. Tracking and recognition of multiple human targets moving in a wireless pyroelectric infrared sensor network.

    PubMed

    Xiong, Ji; Li, Fangmin; Zhao, Ning; Jiang, Na

    2014-04-22

    With characteristics of low-cost and easy deployment, the distributed wireless pyroelectric infrared sensor network has attracted extensive interest, which aims to make it an alternate infrared video sensor in thermal biometric applications for tracking and identifying human targets. In these applications, effectively processing signals collected from sensors and extracting the features of different human targets has become crucial. This paper proposes the application of empirical mode decomposition and the Hilbert-Huang transform to extract features of moving human targets both in the time domain and the frequency domain. Moreover, the support vector machine is selected as the classifier. The experimental results demonstrate that by using this method the identification rates of multiple moving human targets are around 90%.

  17. The Replication Focus Targeting Sequence (RFTS) Domain Is a DNA-competitive Inhibitor of Dnmt1

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

    Syeda, Farisa; Fagan, Rebecca L.; Wean, Matthew

    Dnmt1 (DNA methyltransferase 1) is the principal enzyme responsible for maintenance of cytosine methylation at CpG dinucleotides in the mammalian genome. The N-terminal replication focus targeting sequence (RFTS) domain of Dnmt1 has been implicated in subcellular localization, protein association, and catalytic function. However, progress in understanding its function has been limited by the lack of assays for and a structure of this domain. Here, we show that the naked DNA- and polynucleosome-binding activities of Dnmt1 are inhibited by the RFTS domain, which functions by virtue of binding the catalytic domain to the exclusion of DNA. Kinetic analysis with a fluorogenicmore » DNA substrate established the RFTS domain as a 600-fold inhibitor of Dnmt1 enzymatic activity. The crystal structure of the RFTS domain reveals a novel fold and supports a mechanism in which an RFTS-targeted Dnmt1-binding protein, such as Uhrf1, may activate Dnmt1 for DNA binding.« less

  18. Molecular dynamics simulations elucidate the mode of protein recognition by Skp1 and the F-box domain in the SCF complex.

    PubMed

    Chandra Dantu, Sarath; Nathubhai Kachariya, Nitin; Kumar, Ashutosh

    2016-01-01

    Polyubiquitination of the target protein by a ubiquitin transferring machinery is key to various cellular processes. E3 ligase Skp1-Cul1-F-box (SCF) is one such complex which plays crucial role in substrate recognition and transfer of the ubiquitin molecule. Previous computational studies have focused on S-phase kinase-associated protein 2 (Skp2), cullin, and RING-finger proteins of this complex, but the roles of the adapter protein Skp1 and F-box domain of Skp2 have not been determined. Using sub-microsecond molecular dynamics simulations of full-length Skp1, unbound Skp2, Skp2-Cks1 (Cks1: Cyclin-dependent kinases regulatory subunit 1), Skp1-Skp2, and Skp1-Skp2-Cks1 complexes, we have elucidated the function of Skp1 and the F-box domain of Skp2. We found that the L16 loop of Skp1, which was deleted in previous X-ray crystallography studies, can offer additional stability to the ternary complex via its interactions with the C-terminal tail of Skp2. Moreover, Skp1 helices H6, H7, and H8 display vivid conformational flexibility when not bound to Skp2, suggesting that these helices can recognize and lock the F-box proteins. Furthermore, we observed that the F-box domain could rotate (5°-129°), and that the binding partner determined the degree of conformational flexibility. Finally, Skp1 and Skp2 were found to execute a domain motion in Skp1-Skp2 and Skp1-Skp2-Cks1 complexes that could decrease the distance between ubiquitination site of the substrate and the ubiquitin molecule by 3 nm. Thus, we propose that both the F-box domain of Skp2 and Skp1-Skp2 domain motions displaying preferential conformational control can together facilitate polyubiquitination of a wide variety of substrates. © 2015 Wiley Periodicals, Inc.

  19. DNA Recognition by the DNA Primase of Bacteriophage T7: A Structure Function Study of the Zinc-Binding Domain

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

    Akabayov, B.; Lee, S; Akabayov, S

    2009-01-01

    Synthesis of oligoribonucleotide primers for lagging-strand DNA synthesis in the DNA replication system of bacteriophage T7 is catalyzed by the primase domain of the gene 4 helicase-primase. The primase consists of a zinc-binding domain (ZBD) and an RNA polymerase (RPD) domain. The ZBD is responsible for recognition of a specific sequence in the ssDNA template whereas catalytic activity resides in the RPD. The ZBD contains a zinc ion coordinated with four cysteine residues. We have examined the ligation state of the zinc ion by X-ray absorption spectroscopy and biochemical analysis of genetically altered primases. The ZBD of primase engaged inmore » catalysis exhibits considerable asymmetry in coordination to zinc, as evidenced by a gradual increase in electron density of the zinc together with elongation of the zinc-sulfur bonds. Both wild-type primase and primase reconstituted from purified ZBD and RPD have a similar electronic change in the level of the zinc ion as well as the configuration of the ZBD. Single amino acid replacements in the ZBD (H33A and C36S) result in the loss of both zinc binding and its structural integrity. Thus the zinc in the ZBD may act as a charge modulation indicator for the surrounding sulfur atoms necessary for recognition of specific DNA sequences.« less

  20. Tracking and Recognition of Multiple Human Targets Moving in a Wireless Pyroelectric Infrared Sensor Network

    PubMed Central

    Xiong, Ji; Li, Fangmin; Zhao, Ning; Jiang, Na

    2014-01-01

    With characteristics of low-cost and easy deployment, the distributed wireless pyroelectric infrared sensor network has attracted extensive interest, which aims to make it an alternate infrared video sensor in thermal biometric applications for tracking and identifying human targets. In these applications, effectively processing signals collected from sensors and extracting the features of different human targets has become crucial. This paper proposes the application of empirical mode decomposition and the Hilbert-Huang transform to extract features of moving human targets both in the time domain and the frequency domain. Moreover, the support vector machine is selected as the classifier. The experimental results demonstrate that by using this method the identification rates of multiple moving human targets are around 90%. PMID:24759117

  1. Structural insights into FRS2α PTB domain recognition by neurotrophin receptor TrkB.

    PubMed

    Zeng, Lei; Kuti, Miklos; Mujtaba, Shiraz; Zhou, Ming-Ming

    2014-07-01

    The fibroblast growth factor receptor (FGFR) substrate 2 (FRS2) family proteins function as scaffolding adapters for receptor tyrosine kinases (RTKs). The FRS2α proteins interact with RTKs through the phosphotyrosine-binding (PTB) domain and transfer signals from the activated receptors to downstream effector proteins. Here, we report the nuclear magnetic resonance structure of the FRS2α PTB domain bound to phosphorylated TrkB. The structure reveals that the FRS2α-PTB domain is comprised of two distinct but adjacent pockets for its mutually exclusive interaction with either nonphosphorylated juxtamembrane region of the FGFR, or tyrosine phosphorylated peptides TrkA and TrkB. The new structural insights suggest rational design of selective small molecules through targeting of the two conjunct pockets in the FRS2α PTB domain. © 2014 Wiley Periodicals, Inc.

  2. Solution NMR Analyses of the C-type Carbohydrate Recognition Domain of DC-SIGNR Protein Reveal Different Binding Modes for HIV-derived Oligosaccharides and Smaller Glycan Fragments

    PubMed Central

    Probert, Fay; Whittaker, Sara B.-M.; Crispin, Max; Mitchell, Daniel A.; Dixon, Ann M.

    2013-01-01

    The C-type lectin DC-SIGNR (dendritic cell-specific ICAM-3-grabbing non-integrin-related; also known as L-SIGN or CD299) is a promising drug target due to its ability to promote infection and/or within-host survival of several dangerous pathogens (e.g. HIV and severe acute respiratory syndrome coronavirus (SARS)) via interactions with their surface glycans. Crystallography has provided excellent insight into the mechanism by which DC-SIGNR interacts with small glycans, such as (GlcNAc)2Man3; however, direct observation of complexes with larger, physiological oligosaccharides, such as Man9GlcNAc2, remains elusive. We have utilized solution-state nuclear magnetic resonance spectroscopy to investigate DC-SIGNR binding and herein report the first backbone assignment of its active, calcium-bound carbohydrate recognition domain. Direct interactions with the small sugar fragments Man3, Man5, and (GlcNAc)2Man3 were investigated alongside Man9GlcNAc derived from recombinant gp120 (present on the HIV viral envelope), providing the first structural data for DC-SIGNR in complex with a virus-associated ligand, and unique binding modes were observed for each glycan. In particular, our data show that DC-SIGNR has a different binding mode for glycans on the HIV viral envelope compared with the smaller glycans previously observed in the crystalline state. This suggests that using the binding mode of Man9GlcNAc, instead of those of small glycans, may provide a platform for the design of DC-SIGNR inhibitors selective for high mannose glycans (like those on HIV). 15N relaxation measurements provided the first information on the dynamics of the carbohydrate recognition domain, demonstrating that it is a highly flexible domain that undergoes ligand-induced conformational and dynamic changes that may explain the ability of DC-SIGNR to accommodate a range of glycans on viral surfaces. PMID:23788638

  3. Automatic target recognition apparatus and method

    DOEpatents

    Baumgart, Chris W.; Ciarcia, Christopher A.

    2000-01-01

    An automatic target recognition apparatus (10) is provided, having a video camera/digitizer (12) for producing a digitized image signal (20) representing an image containing therein objects which objects are to be recognized if they meet predefined criteria. The digitized image signal (20) is processed within a video analysis subroutine (22) residing in a computer (14) in a plurality of parallel analysis chains such that the objects are presumed to be lighter in shading than the background in the image in three of the chains and further such that the objects are presumed to be darker than the background in the other three chains. In two of the chains the objects are defined by surface texture analysis using texture filter operations. In another two of the chains the objects are defined by background subtraction operations. In yet another two of the chains the objects are defined by edge enhancement processes. In each of the analysis chains a calculation operation independently determines an error factor relating to the probability that the objects are of the type which should be recognized, and a probability calculation operation combines the results of the analysis chains.

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

    NASA Astrophysics Data System (ADS)

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

    1990-09-01

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

  5. Social-cognitive remediation in schizophrenia: generalization of effects of the Training of Affect Recognition (TAR).

    PubMed

    Wölwer, Wolfgang; Frommann, Nicole

    2011-09-01

    In the last decade, several social cognitive remediation programs have been developed for use in schizophrenia. Though existing evidence indicates that such programs can improve social cognition, which is essential for successful social functioning, it remains unclear whether the improvements generalize to social cognitive domains not primarily addressed by the intervention and whether the improved test performance transfers into everyday social functioning. The present study investigated whether, beyond its known effects on facial affect recognition, the Training of Affect Recognition (TAR) has effects on prosodic affect recognition, theory of mind (ToM) performance, social competence in a role-play task, and more general social and occupational functioning. Thirty-eight inpatients with a diagnosis of schizophrenia or schizoaffective disorder were randomly assigned to 6 weeks of treatment with the TAR--primarily targeted at facial affect recognition-or Cognitive Remediation Training (CRT)--primarily targeted at neurocognition. Intention-to-treat analyses found significantly larger pre-post improvements with TAR than with CRT in prosodic affect recognition, ToM, and social competence and a trend effect in global social functioning. However, the effects on ToM and social competence were no longer significant in the smaller group of patients who completed treatment according to protocol. Results suggest that TAR effects generalize to other social cognitive domains not primarily addressed. TAR may also enhance social skills and social functioning, although this has to be confirmed. Results are discussed with regard to the need to improve functional outcome in schizophrenia against the background of current evidence from other social cognitive remediation approaches.

  6. Infrared target recognition based on improved joint local ternary pattern

    NASA Astrophysics Data System (ADS)

    Sun, Junding; Wu, Xiaosheng

    2016-05-01

    This paper presents a simple, efficient, yet robust approach, named joint orthogonal combination of local ternary pattern, for automatic forward-looking infrared target recognition. It gives more advantages to describe the macroscopic textures and microscopic textures by fusing variety of scales than the traditional LBP-based methods. In addition, it can effectively reduce the feature dimensionality. Further, the rotation invariant and uniform scheme, the robust LTP, and soft concave-convex partition are introduced to enhance its discriminative power. Experimental results demonstrate that the proposed method can achieve competitive results compared with the state-of-the-art methods.

  7. Author name recognition in degraded journal images

    NASA Astrophysics Data System (ADS)

    de Bodard de la Jacopière, Aliette; Likforman-Sulem, Laurence

    2006-01-01

    A method for extracting names in degraded documents is presented in this article. The documents targeted are images of photocopied scientific journals from various scientific domains. Due to the degradation, there is poor OCR recognition, and pieces of other articles appear on the sides of the image. The proposed approach relies on the combination of a low-level textual analysis and an image-based analysis. The textual analysis extracts robust typographic features, while the image analysis selects image regions of interest through anchor components. We report results on the University of Washington benchmark database.

  8. Invariant-feature-based adaptive automatic target recognition in obscured 3D point clouds

    NASA Astrophysics Data System (ADS)

    Khuon, Timothy; Kershner, Charles; Mattei, Enrico; Alverio, Arnel; Rand, Robert

    2014-06-01

    Target recognition and classification in a 3D point cloud is a non-trivial process due to the nature of the data collected from a sensor system. The signal can be corrupted by noise from the environment, electronic system, A/D converter, etc. Therefore, an adaptive system with a desired tolerance is required to perform classification and recognition optimally. The feature-based pattern recognition algorithm architecture as described below is particularly devised for solving a single-sensor classification non-parametrically. Feature set is extracted from an input point cloud, normalized, and classifier a neural network classifier. For instance, automatic target recognition in an urban area would require different feature sets from one in a dense foliage area. The figure above (see manuscript) illustrates the architecture of the feature based adaptive signature extraction of 3D point cloud including LIDAR, RADAR, and electro-optical data. This network takes a 3D cluster and classifies it into a specific class. The algorithm is a supervised and adaptive classifier with two modes: the training mode and the performing mode. For the training mode, a number of novel patterns are selected from actual or artificial data. A particular 3D cluster is input to the network as shown above for the decision class output. The network consists of three sequential functional modules. The first module is for feature extraction that extracts the input cluster into a set of singular value features or feature vector. Then the feature vector is input into the feature normalization module to normalize and balance it before being fed to the neural net classifier for the classification. The neural net can be trained by actual or artificial novel data until each trained output reaches the declared output within the defined tolerance. In case new novel data is added after the neural net has been learned, the training is then resumed until the neural net has incrementally learned with the new

  9. Differential recognition of syk-binding sites by each of the two phosphotyrosine-binding pockets of the Vav SH2 domain.

    PubMed

    Chen, Chih-Hong; Piraner, Dan; Gorenstein, Nina M; Geahlen, Robert L; Beth Post, Carol

    2013-11-01

    The association of spleen tyrosine kinase (Syk), a central tyrosine kinase in B cell signaling, with Vav SH2 domain is controlled by phosphorylation of two closely spaced tyrosines in Syk linker B: Y342 and Y346. Previous studies established both singly phosphorylated and doubly phosphorylated forms play a role in signaling. The structure of the doubly phosphorylated form identified a new recognition of phosphotyrosine whereby two phosphotyrosines bind simultaneously to the Vav SH2 domain, one in the canonical pTyr pocket and one in the specificity pocket on the opposite side of the central β-sheet. It is unknown if the specificity pocket can bind phosphotyrosine independent of phosphotyrosine binding the pTyr pocket. To address this gap in knowledge, we determined the structure of the complex between Vav1 SH2 and a peptide (SykLB-YpY) modeling the singly phosphorylated-Y346 form of Syk with unphosphorylated Y342. The nuclear magnetic resonance (NMR) data conclusively establish that recognition of phosphotyrosine is swapped between the two pockets; phosphorylated pY346 binds the specificity pocket of Vav1 SH2, and unphosphorylated Y342 occupies what is normally the pTyr binding pocket. Nearly identical changes in chemical shifts occurred upon binding all three forms of singly and doubly phosphorylated peptides; however, somewhat smaller shift perturbations for SykLB-YpY from residues in regions of high internal mobility suggest that internal motions are coupled to binding affinity. The differential recognition that includes this swapped binding of phosphotyrosine to the specificity pocket of Vav SH2 increases the repertoire of possible phosphotyrosine binding by SH2 domains in regulating protein-protein interactions in cellular signaling. Copyright © 2013 Wiley Periodicals, Inc.

  10. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    PubMed Central

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-01-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding. PMID:10727405

  11. The heparin-binding site in tetranectin is located in the N-terminal region and binding does not involve the carbohydrate recognition domain.

    PubMed

    Lorentsen, R H; Graversen, J H; Caterer, N R; Thogersen, H C; Etzerodt, M

    2000-04-01

    Tetranectin is a homotrimeric plasma and extracellular-matrix protein that binds plasminogen and complex sulphated polysaccharides including heparin. In terms of primary and tertiary structure, tetranectin is related to the collectin family of Ca(2+)-binding C-type lectins. Tetranectin is encoded in three exons. Exon 3 encodes the carbohydrate recognition domain, which binds to kringle 4 in plasminogen at low levels of Ca(2+). Exon 2 encodes an alpha-helix, which is necessary and sufficient to govern the trimerization of tetranectin by assembling into a triple-helical coiled-coil structural element. Here we show that the heparin-binding site in tetranectin resides not in the carbohydrate recognition domain but within the N-terminal region, comprising the 16 amino acid residues encoded by exon 1. In particular, the lysine residues in the decapeptide segment KPKKIVNAKK (tetranectin residues 6-15) are shown to be of primary importance in heparin binding.

  12. Mechanistic insights into the recognition of 5-methylcytosine oxidation derivatives by the SUVH5 SRA domain.

    PubMed

    Rajakumara, Eerappa; Nakarakanti, Naveen Kumar; Nivya, M Angel; Satish, Mutyala

    2016-02-04

    5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context of a CG sequence by the SET- and RING-associated domain (SRA) of the SUVH5 protein (SUVH5 SRA). Using calorimetric measurements, we demonstrate that the SRA domain binds to the hydroxymethylated CG (5hmCG) DNA duplex in a similar manner to methylated CG (5mCG). Interestingly, the SUVH5 SRA domain exhibits weaker affinity towards carboxylated CG (5caCG) and formylated CG (5fCG). We report the 2.6 Å resolution crystal structure of the SUVH5 SRA domain in a complex with fully hydroxymethyl-CG and demonstrate a dual flip-out mechanism, whereby the symmetrical 5hmCs are simultaneously extruded from the partner strands of the DNA duplex and are positioned within the binding pockets of individual SRA domains. The hydroxyl group of 5hmC establishes both intra- and intermolecular interactions in the binding pocket. Collectively, we show that SUVH5 SRA recognizes 5hmC in a similar manner to 5 mC, but exhibits weaker affinity towards 5 hmC oxidation derivatives.

  13. Offline Arabic handwriting recognition: a survey.

    PubMed

    Lorigo, Liana M; Govindaraju, Venu

    2006-05-01

    The automatic recognition of text on scanned images has enabled many applications such as searching for words in large volumes of documents, automatic sorting of postal mail, and convenient editing of previously printed documents. The domain of handwriting in the Arabic script presents unique technical challenges and has been addressed more recently than other domains. Many different methods have been proposed and applied to various types of images. This paper provides a comprehensive review of these methods. It is the first survey to focus on Arabic handwriting recognition and the first Arabic character recognition survey to provide recognition rates and descriptions of test data for the approaches discussed. It includes background on the field, discussion of the methods, and future research directions.

  14. Recognition of extremophilic archaeal viruses by eukaryotic cells: a promising nanoplatform from the third domain of life

    PubMed Central

    Uldahl, Kristine Buch; Wu, Linping; Hall, Arnaldur; Papathanasiou, Pavlos; Peng, Xu; Moghimi, Seyed Moein

    2016-01-01

    Viruses from the third domain of life, Archaea, exhibit unusual features including extreme stability that allow their survival in harsh environments. In addition, these species have never been reported to integrate into human or any other eukaryotic genomes, and could thus serve for exploration of novel medical nanoplatforms. Here, we selected two archaeal viruses Sulfolobus monocaudavirus 1 (SMV1) and Sulfolobus spindle shaped virus 2 (SSV2) owing to their unique spindle shape, hyperthermostable and acid-resistant nature and studied their interaction with mammalian cells. Accordingly, we followed viral uptake, intracellular trafficking and cell viability in human endothelial cells of brain (hCMEC/D3 cells) and umbilical vein (HUVEC) origin. Whereas SMV1 is efficiently internalized into both types of human cells, SSV2 differentiates between HUVECs and hCMEC/D3 cells, thus opening a path for selective cell targeting. On internalization, both viruses localize to the lysosomal compartments. Neither SMV1, nor SSV2 induced any detrimental effect on cell morphology, plasma membrane and mitochondrial functionality. This is the first study demonstrating recognition of archaeal viruses by eukaryotic cells which provides good basis for future exploration of archaeal viruses in bioengineering and development of multifunctional vectors. PMID:27892499

  15. Target recognition and scene interpretation in image/video understanding systems based on network-symbolic models

    NASA Astrophysics Data System (ADS)

    Kuvich, Gary

    2004-08-01

    Vision is only a part of a system that converts visual information into knowledge structures. These structures drive the vision process, resolving ambiguity and uncertainty via feedback, and provide image understanding, which is an interpretation of visual information in terms of these knowledge models. These mechanisms provide a reliable recognition if the object is occluded or cannot be recognized as a whole. It is hard to split the entire system apart, and reliable solutions to the target recognition problems are possible only within the solution of a more generic Image Understanding Problem. Brain reduces informational and computational complexities, using implicit symbolic coding of features, hierarchical compression, and selective processing of visual information. Biologically inspired Network-Symbolic representation, where both systematic structural/logical methods and neural/statistical methods are parts of a single mechanism, is the most feasible for such models. It converts visual information into relational Network-Symbolic structures, avoiding artificial precise computations of 3-dimensional models. Network-Symbolic Transformations derive abstract structures, which allows for invariant recognition of an object as exemplar of a class. Active vision helps creating consistent models. Attention, separation of figure from ground and perceptual grouping are special kinds of network-symbolic transformations. Such Image/Video Understanding Systems will be reliably recognizing targets.

  16. Target Control in Logical Models Using the Domain of Influence of Nodes.

    PubMed

    Yang, Gang; Gómez Tejeda Zañudo, Jorge; Albert, Réka

    2018-01-01

    Dynamical models of biomolecular networks are successfully used to understand the mechanisms underlying complex diseases and to design therapeutic strategies. Network control and its special case of target control, is a promising avenue toward developing disease therapies. In target control it is assumed that a small subset of nodes is most relevant to the system's state and the goal is to drive the target nodes into their desired states. An example of target control would be driving a cell to commit to apoptosis (programmed cell death). From the experimental perspective, gene knockout, pharmacological inhibition of proteins, and providing sustained external signals are among practical intervention techniques. We identify methodologies to use the stabilizing effect of sustained interventions for target control in Boolean network models of biomolecular networks. Specifically, we define the domain of influence (DOI) of a node (in a certain state) to be the nodes (and their corresponding states) that will be ultimately stabilized by the sustained state of this node regardless of the initial state of the system. We also define the related concept of the logical domain of influence (LDOI) of a node, and develop an algorithm for its identification using an auxiliary network that incorporates the regulatory logic. This way a solution to the target control problem is a set of nodes whose DOI can cover the desired target node states. We perform greedy randomized adaptive search in node state space to find such solutions. We apply our strategy to in silico biological network models of real systems to demonstrate its effectiveness.

  17. Increase in Speech Recognition Due to Linguistic Mismatch between Target and Masker Speech: Monolingual and Simultaneous Bilingual Performance

    ERIC Educational Resources Information Center

    Calandruccio, Lauren; Zhou, Haibo

    2014-01-01

    Purpose: To examine whether improved speech recognition during linguistically mismatched target-masker experiments is due to linguistic unfamiliarity of the masker speech or linguistic dissimilarity between the target and masker speech. Method: Monolingual English speakers (n = 20) and English-Greek simultaneous bilinguals (n = 20) listened to…

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

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin

    1992-01-01

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

  19. Structural basis of molecular recognition of helical histone H3 tail by PHD finger domains.

    PubMed

    Bortoluzzi, Alessio; Amato, Anastasia; Lucas, Xavier; Blank, Manuel; Ciulli, Alessio

    2017-05-04

    The plant homeodomain (PHD) fingers are among the largest family of epigenetic domains, first characterized as readers of methylated H3K4. Readout of histone post-translational modifications by PHDs has been the subject of intense investigation; however, less is known about the recognition of secondary structure features within the histone tail itself. We solved the crystal structure of the PHD finger of the bromodomain adjacent to zinc finger 2A [BAZ2A, also known as TIP5 (TTF-I/interacting protein 5)] in complex with unmodified N-terminal histone H3 tail. The peptide is bound in a helical folded-back conformation after K4, induced by an acidic patch on the protein surface that prevents peptide binding in an extended conformation. Structural bioinformatics analyses identify a conserved Asp/Glu residue that we name 'acidic wall', found to be mutually exclusive with the conserved Trp for K4Me recognition. Neutralization or inversion of the charges at the acidic wall patch in BAZ2A, and homologous BAZ2B, weakened H3 binding. We identify simple mutations on H3 that strikingly enhance or reduce binding, as a result of their stabilization or destabilization of H3 helicity. Our work unravels the structural basis for binding of the helical H3 tail by PHD fingers and suggests that molecular recognition of secondary structure motifs within histone tails could represent an additional layer of regulation in epigenetic processes. © 2017 The Author(s).

  20. GRP1 PH Domain, Like AKT1 PH Domain, Possesses a Sentry Glutamate Residue Essential for Specific Targeting to Plasma Membrane PI(3,4,5)P3

    PubMed Central

    Pilling, Carissa; Landgraf, Kyle E.; Falke, Joseph J.

    2011-01-01

    During the appearance of the signaling lipid PI(3,4,5)P3, an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P3-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P2 and bind the rare PI(3,4,5)P3 target lipid with sufficiently high affinity. Our previous study of the E17K mutant of protein kinase B (AKT1) PH domain, together with evidence from Carpten et al (1), revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P2, thereby playing an essential role in specific PI(3,4,5)P3 targeting (2). The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P3-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P2 affinity and constitutive plasma membrane targeting. To test this hypothesis the present study investigates the E345 residue, a putative sentry glutamate, of General Receptor for Phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into GRP1 PH domain enhances PI(4,5)P2 affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P2 releases E345K GRP1 PH domain into the cytoplasm and the efficiency of this release increases when target Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K (1, 3). Analysis of available PH domain structures suggests that a lone glutamate residue (or, in some cases an aspartate) is a common, perhaps ubiquitous, feature of PI(3,4,5)P3-specific binding

  1. Structure–function studies of STAR family Quaking proteins bound to their in vivo RNA target sites

    PubMed Central

    Teplova, Marianna; Hafner, Markus; Teplov, Dmitri; Essig, Katharina; Tuschl, Thomas; Patel, Dinshaw J.

    2013-01-01

    Mammalian Quaking (QKI) and its Caenorhabditis elegans homolog, GLD-1 (defective in germ line development), are evolutionarily conserved RNA-binding proteins, which post-transcriptionally regulate target genes essential for developmental processes and myelination. We present X-ray structures of the STAR (signal transduction and activation of RNA) domain, composed of Qua1, K homology (KH), and Qua2 motifs of QKI and GLD-1 bound to high-affinity in vivo RNA targets containing YUAAY RNA recognition elements (RREs). The KH and Qua2 motifs of the STAR domain synergize to specifically interact with bases and sugar-phosphate backbones of the bound RRE. Qua1-mediated homodimerization generates a scaffold that enables concurrent recognition of two RREs, thereby plausibly targeting tandem RREs present in many QKI-targeted transcripts. Structure-guided mutations reduced QKI RNA-binding affinity in vitro and in vivo, and expression of QKI mutants in human embryonic kidney cells (HEK293) significantly decreased the abundance of QKI target mRNAs. Overall, our studies define principles underlying RNA target selection by STAR homodimers and provide insights into the post-transcriptional regulatory function of mammalian QKI proteins. PMID:23630077

  2. Mechanistic insights into the recognition of 5-methylcytosine oxidation derivatives by the SUVH5 SRA domain

    PubMed Central

    Rajakumara, Eerappa; Nakarakanti, Naveen Kumar; Nivya, M. Angel; Satish, Mutyala

    2016-01-01

    5-Methylcytosine (5 mC) is associated with epigenetic gene silencing in mammals and plants. 5 mC is consecutively oxidized to 5-hydroxymethylcytosine (5 hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC) by ten-eleven translocation enzymes. We performed binding and structural studies to investigate the molecular basis of the recognition of the 5 mC oxidation derivatives in the context of a CG sequence by the SET- and RING-associated domain (SRA) of the SUVH5 protein (SUVH5 SRA). Using calorimetric measurements, we demonstrate that the SRA domain binds to the hydroxymethylated CG (5hmCG) DNA duplex in a similar manner to methylated CG (5mCG). Interestingly, the SUVH5 SRA domain exhibits weaker affinity towards carboxylated CG (5caCG) and formylated CG (5fCG). We report the 2.6 Å resolution crystal structure of the SUVH5 SRA domain in a complex with fully hydroxymethyl-CG and demonstrate a dual flip-out mechanism, whereby the symmetrical 5hmCs are simultaneously extruded from the partner strands of the DNA duplex and are positioned within the binding pockets of individual SRA domains. The hydroxyl group of 5hmC establishes both intra- and intermolecular interactions in the binding pocket. Collectively, we show that SUVH5 SRA recognizes 5hmC in a similar manner to 5 mC, but exhibits weaker affinity towards 5 hmC oxidation derivatives. PMID:26841909

  3. Lectin-Binding Specificity of the Fertilization-Relevant Protein PDC-109 by Means of Surface Plasmon Resonance and Carbohydrate REcognition Domain EXcision-Mass Spectrometry.

    PubMed

    Defaus, Sira; Avilés, Manuel; Andreu, David; Gutiérrez-Gallego, Ricardo

    2018-04-04

    Seminal plasma proteins are relevant for sperm functionality and some appear responsible for establishing sperm interactions with the various environments along the female genital tract towards the oocyte. In recent years, research has focused on characterizing the role of these proteins in the context of reproductive biology, fertility diagnostics and treatment of related problems. Herein, we focus on the main protein of bovine seminal plasma, PDC-109 (BSP-A1/-A2), which by virtue of its lectin properties is involved in fertilization. By means of surface plasmon resonance, the interaction of PDC-109 with a panel of the most relevant glycosidic epitopes of mammals has been qualitatively and quantitatively characterized, and a higher affinity for carbohydrates containing fucose has been observed, in line with previous studies. Additionally, using the orthogonal technique of Carbohydrate REcognition Domain EXcision-Mass Spectrometry (CREDEX-MS), the recognition domain of the interaction complexes between PDC-109 and all fucosylated disaccharides [(Fuc-α1,(3,4,6)-GlcNAc)] has been defined, revealing the specific glycotope and the peptide domain likely to act as the PDC-109 carbohydrate binding site.

  4. Quantifying domain-ligand affinities and specificities by high-throughput holdup assay

    PubMed Central

    Vincentelli, Renaud; Luck, Katja; Poirson, Juline; Polanowska, Jolanta; Abdat, Julie; Blémont, Marilyne; Turchetto, Jeremy; Iv, François; Ricquier, Kevin; Straub, Marie-Laure; Forster, Anne; Cassonnet, Patricia; Borg, Jean-Paul; Jacob, Yves; Masson, Murielle; Nominé, Yves; Reboul, Jérôme; Wolff, Nicolas; Charbonnier, Sebastian; Travé, Gilles

    2015-01-01

    Many protein interactions are mediated by small linear motifs interacting specifically with defined families of globular domains. Quantifying the specificity of a motif requires measuring and comparing its binding affinities to all its putative target domains. To this aim, we developed the high-throughput holdup assay, a chromatographic approach that can measure up to a thousand domain-motif equilibrium binding affinities per day. Extracts of overexpressed domains are incubated with peptide-coated resins and subjected to filtration. Binding affinities are deduced from microfluidic capillary electrophoresis of flow-throughs. After benchmarking the approach on 210 PDZ-peptide pairs with known affinities, we determined the affinities of two viral PDZ-binding motifs derived from Human Papillomavirus E6 oncoproteins for 209 PDZ domains covering 79% of the human PDZome. We obtained exquisite sequence-dependent binding profiles, describing quantitatively the PDZome recognition specificity of each motif. This approach, applicable to many categories of domain-ligand interactions, has a wide potential for quantifying the specificities of interactomes. PMID:26053890

  5. Recurrent neural networks with specialized word embeddings for health-domain named-entity recognition.

    PubMed

    Jauregi Unanue, Iñigo; Zare Borzeshi, Ehsan; Piccardi, Massimo

    2017-12-01

    Previous state-of-the-art systems on Drug Name Recognition (DNR) and Clinical Concept Extraction (CCE) have focused on a combination of text "feature engineering" and conventional machine learning algorithms such as conditional random fields and support vector machines. However, developing good features is inherently heavily time-consuming. Conversely, more modern machine learning approaches such as recurrent neural networks (RNNs) have proved capable of automatically learning effective features from either random assignments or automated word "embeddings". (i) To create a highly accurate DNR and CCE system that avoids conventional, time-consuming feature engineering. (ii) To create richer, more specialized word embeddings by using health domain datasets such as MIMIC-III. (iii) To evaluate our systems over three contemporary datasets. Two deep learning methods, namely the Bidirectional LSTM and the Bidirectional LSTM-CRF, are evaluated. A CRF model is set as the baseline to compare the deep learning systems to a traditional machine learning approach. The same features are used for all the models. We have obtained the best results with the Bidirectional LSTM-CRF model, which has outperformed all previously proposed systems. The specialized embeddings have helped to cover unusual words in DrugBank and MedLine, but not in the i2b2/VA dataset. We present a state-of-the-art system for DNR and CCE. Automated word embeddings has allowed us to avoid costly feature engineering and achieve higher accuracy. Nevertheless, the embeddings need to be retrained over datasets that are adequate for the domain, in order to adequately cover the domain-specific vocabulary. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Targeting a KH-domain protein with RNA decoys.

    PubMed

    Makeyev, Aleksandr V; Eastmond, Dawn L; Liebhaber, Stephen A

    2002-09-01

    RNA-binding proteins are involved in the regulation of many aspects of eukaryotic gene expression. Targeted interference with RNA-protein interactions could offer novel approaches to modulation of expression profiles, alteration of developmental pathways, and reversal of certain disease processes. Here we investigate a decoy strategy for the study of the alphaCP subgroup of KH-domain RNA-binding proteins. These poly(C)-binding proteins have been implicated in a wide spectrum of posttranscriptional controls. Three categories of RNA decoys to alphaCPs were studied: poly(C) homopolymers, native mRNA-binding sites, and a high-affinity structure selected from a combinatorial library. Native chemistry was found to be essential for alphaCP decoy action. Because alphaCP proteins are found in both the nucleus and cytoplasm, decoy cassettes were incorporated within both nuclear (U1 snRNA) and cytoplasmic (VA1 RNA) RNA frameworks. Several sequences demonstrated optimal decoy properties when assayed for protein-binding and decoy bioactivity in vitro. A subset of these transcripts was shown to mediate targeted inhibition of alphaCP-dependent translation when expressed in either the nucleus or cytoplasm of transfected cells. Significantly, these studies establish the feasibility of developing RNA decoys that can selectively target biologic functions of abundant and widely expressed RNA binding proteins.

  7. Targeting a KH-domain protein with RNA decoys.

    PubMed Central

    Makeyev, Aleksandr V; Eastmond, Dawn L; Liebhaber, Stephen A

    2002-01-01

    RNA-binding proteins are involved in the regulation of many aspects of eukaryotic gene expression. Targeted interference with RNA-protein interactions could offer novel approaches to modulation of expression profiles, alteration of developmental pathways, and reversal of certain disease processes. Here we investigate a decoy strategy for the study of the alphaCP subgroup of KH-domain RNA-binding proteins. These poly(C)-binding proteins have been implicated in a wide spectrum of posttranscriptional controls. Three categories of RNA decoys to alphaCPs were studied: poly(C) homopolymers, native mRNA-binding sites, and a high-affinity structure selected from a combinatorial library. Native chemistry was found to be essential for alphaCP decoy action. Because alphaCP proteins are found in both the nucleus and cytoplasm, decoy cassettes were incorporated within both nuclear (U1 snRNA) and cytoplasmic (VA1 RNA) RNA frameworks. Several sequences demonstrated optimal decoy properties when assayed for protein-binding and decoy bioactivity in vitro. A subset of these transcripts was shown to mediate targeted inhibition of alphaCP-dependent translation when expressed in either the nucleus or cytoplasm of transfected cells. Significantly, these studies establish the feasibility of developing RNA decoys that can selectively target biologic functions of abundant and widely expressed RNA binding proteins. PMID:12358435

  8. Computer-Assisted Face Processing Instruction Improves Emotion Recognition, Mentalizing, and Social Skills in Students with ASD.

    PubMed

    Rice, Linda Marie; Wall, Carla Anne; Fogel, Adam; Shic, Frederick

    2015-07-01

    This study examined the extent to which a computer-based social skills intervention called FaceSay was associated with improvements in affect recognition, mentalizing, and social skills of school-aged children with Autism Spectrum Disorder (ASD). FaceSay offers students simulated practice with eye gaze, joint attention, and facial recognition skills. This randomized control trial included school-aged children meeting educational criteria for autism (N = 31). Results demonstrated that participants who received the intervention improved their affect recognition and mentalizing skills, as well as their social skills. These findings suggest that, by targeting face-processing skills, computer-based interventions may produce changes in broader cognitive and social-skills domains in a cost- and time-efficient manner.

  9. Non-canonical binding interactions of the RNA recognition motif (RRM) domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP).

    PubMed

    Kamina, Anyango D; Williams, Noreen

    2017-01-01

    RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains' interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP) 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP.

  10. Diversity in the architecture of ATLs, a family of plant ubiquitin-ligases, leads to recognition and targeting of substrates in different cellular environments.

    PubMed

    Aguilar-Hernández, Victor; Aguilar-Henonin, Laura; Guzmán, Plinio

    2011-01-01

    Ubiquitin-ligases or E3s are components of the ubiquitin proteasome system (UPS) that coordinate the transfer of ubiquitin to the target protein. A major class of ubiquitin-ligases consists of RING-finger domain proteins that include the substrate recognition sequences in the same polypeptide; these are known as single-subunit RING finger E3s. We are studying a particular family of RING finger E3s, named ATL, that contain a transmembrane domain and the RING-H2 finger domain; none of the member of the family contains any other previously described domain. Although the study of a few members in A. thaliana and O. sativa has been reported, the role of this family in the life cycle of a plant is still vague. To provide tools to advance on the functional analysis of this family we have undertaken a phylogenetic analysis of ATLs in twenty-four plant genomes. ATLs were found in all the 24 plant species analyzed, in numbers ranging from 20-28 in two basal species to 162 in soybean. Analysis of ATLs arrayed in tandem indicates that sets of genes are expanding in a species-specific manner. To get insights into the domain architecture of ATLs we generated 75 pHMM LOGOs from 1815 ATLs, and unraveled potential protein-protein interaction regions by means of yeast two-hybrid assays. Several ATLs were found to interact with DSK2a/ubiquilin through a region at the amino-terminal end, suggesting that this is a widespread interaction that may assist in the mode of action of ATLs; the region was traced to a distinct sequence LOGO. Our analysis provides significant observations on the evolution and expansion of the ATL family in addition to information on the domain structure of this class of ubiquitin-ligases that may be involved in plant adaptation to environmental stress.

  11. Crystal Structure of the Human, FIC-Domain Containing Protein HYPE and Implications for Its Functions

    PubMed Central

    Bunney, Tom D.; Cole, Ambrose R.; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W.; Katan, Matilda

    2014-01-01

    Summary Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein, HYPE, which has remained poorly characterized. Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of autoAMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition. PMID:25435325

  12. Crystal structure of the human, FIC-domain containing protein HYPE and implications for its functions.

    PubMed

    Bunney, Tom D; Cole, Ambrose R; Broncel, Malgorzata; Esposito, Diego; Tate, Edward W; Katan, Matilda

    2014-12-02

    Protein AMPylation, the transfer of AMP from ATP to protein targets, has been recognized as a new mechanism of host-cell disruption by some bacterial effectors that typically contain a FIC-domain. Eukaryotic genomes also encode one FIC-domain protein,HYPE, which has remained poorly characterized.Here we describe the structure of human HYPE, solved by X-ray crystallography, representing the first structure of a eukaryotic FIC-domain protein. We demonstrate that HYPE forms stable dimers with structurally and functionally integrated FIC-domains and with TPR-motifs exposed for protein-protein interactions. As HYPE also uniquely possesses a transmembrane helix, dimerization is likely to affect its positioning and function in the membrane vicinity. The low rate of auto AMPylation of the wild-type HYPE could be due to autoinhibition, consistent with the mechanism proposed for a number of putative FIC AMPylators. Our findings also provide a basis to further consider possible alternative cofactors of HYPE and distinct modes of target-recognition.

  13. ADAM disintegrin-like domain recognition by the lymphocyte integrins α4β1 and α4β7

    PubMed Central

    Bridges, Lance C.; Sheppard, Dean; Bowditch, Ron D.

    2004-01-01

    The ADAM (a disintegrin and metalloprotease) family of proteins possess both proteolytic and adhesive domains. We have established previously that the disintegrin domain of ADAM28, an ADAM expressed by human lymphocytes, is recognized by the integrin α4β1. The present study characterizes the integrin binding properties of the disintegrin-like domains of human ADAM7, ADAM28 and ADAM33 with the integrins α4β1, α4β7 and α9β1. Cell-adhesion assays demonstrated that, similar to ADAM28, the ADAM7 disintegrin domain supported α4β1-dependent Jurkat cell adhesion, whereas the ADAM33 disintegrin domain did not. The lymphocyte integrin α4β7 was also found to recognize both disintegrin domains of ADAM7 and ADAM28, but not of ADAM33. This is the first demonstration that mammalian disintegrins are capable of interacting with α4β7. All three disintegrin domains supported α9β1-dependent cell adhesion. Recognition by both α4β1 and α4β7 of ADAM7 and ADAM28 was activation-dependent, requiring either the presence of Mn2+ or an activating monoclonal antibody for cell attachment. Charge-to-alanine mutagenesis experiments revealed that the same residues within an individual ADAM disintegrin domain function in recognizing multiple integrins. However, the residues within a specific region of each ADAM disintegrin-like domain required for integrin binding were distinct. These results establish that ADAM7 and ADAM28 are recognized by the leucocyte integrins α4β1, α4β7 and α9β1. ADAM33 exclusively supported only α9β1-dependent adhesion. PMID:15504110

  14. SAR target recognition using behaviour library of different shapes in different incidence angles and polarisations

    NASA Astrophysics Data System (ADS)

    Fallahpour, Mojtaba Behzad; Dehghani, Hamid; Jabbar Rashidi, Ali; Sheikhi, Abbas

    2018-05-01

    Target recognition is one of the most important issues in the interpretation of the synthetic aperture radar (SAR) images. Modelling, analysis, and recognition of the effects of influential parameters in the SAR can provide a better understanding of the SAR imaging systems, and therefore facilitates the interpretation of the produced images. Influential parameters in SAR images can be divided into five general categories of radar, radar platform, channel, imaging region, and processing section, each of which has different physical, structural, hardware, and software sub-parameters with clear roles in the finally formed images. In this paper, for the first time, a behaviour library that includes the effects of polarisation, incidence angle, and shape of targets, as radar and imaging region sub-parameters, in the SAR images are extracted. This library shows that the created pattern for each of cylindrical, conical, and cubic shapes is unique, and due to their unique properties these types of shapes can be recognised in the SAR images. This capability is applied to data acquired with the Canadian RADARSAT1 satellite.

  15. RecceMan: an interactive recognition assistance for image-based reconnaissance: synergistic effects of human perception and computational methods for object recognition, identification, and infrastructure analysis

    NASA Astrophysics Data System (ADS)

    El Bekri, Nadia; Angele, Susanne; Ruckhäberle, Martin; Peinsipp-Byma, Elisabeth; Haelke, Bruno

    2015-10-01

    infrastructure analysis mode pursues the goal to analyze the function of the infrastructure. The image analyst extracts visually certain target object signatures, assigns them to corresponding object features and is finally able to recognize the object type. The system offers him the possibility to assign the image signatures to features given by sample images. The underlying data set contains a wide range of objects features and object types for different domains like ships or land vehicles. Each domain has its own feature tree developed by aerial image analyst experts. By selecting the corresponding features, the possible solution set of objects is automatically reduced and matches only the objects that contain the selected features. Moreover, we give an outlook of current research in the field of ground target analysis in which we deal with partly automated methods to extract image signatures and assign them to the corresponding features. This research includes methods for automatically determining the orientation of an object and geometric features like width and length of the object. This step enables to reduce automatically the possible object types offered to the image analyst by the interactive recognition assistance system.

  16. Intracellular Protein Delivery System Using a Target-Specific Repebody and Translocation Domain of Bacterial Exotoxin.

    PubMed

    Kim, Hee-Yeon; Kang, Jung Ae; Ryou, Jeong-Hyun; Lee, Gyeong Hee; Choi, Dae Seong; Lee, Dong Eun; Kim, Hak-Sung

    2017-11-17

    With the high efficacy of protein-based therapeutics and plenty of intracellular drug targets, cytosolic protein delivery in a cell-specific manner has attracted considerable attention in the field of precision medicine. Herein, we present an intracellular protein delivery system based on a target-specific repebody and the translocation domain of Pseudomonas aeruginosa exotoxin A. The delivery platform was constructed by genetically fusing an EGFR-specific repebody as a targeting moiety to the translocation domain, while a protein cargo was fused to the C-terminal end of the delivery platform. The delivery platform was revealed to efficiently translocate a protein cargo to the cytosol in a target-specific manner. We demonstrate the utility and potential of the delivery platform by showing a remarkable tumor regression with negligible toxicity in a xenograft mice model when gelonin was used as the cytotoxic protein cargo. The present platform can find wide applications to the cell-selective cytosolic delivery of diverse proteins in many areas.

  17. Pattern recognition of the targets with help of polarization properties of the signal

    NASA Astrophysics Data System (ADS)

    Ponomaryov, Volodymyr I.; de Rivera, Luis N.; Castellanos, Aldo B.; Popov, Anatoly V.

    1999-10-01

    We proposed to use the possibility of recognition of the targets on background of the scattering from the surface, weather objects with the help of polarimetric 3-cm radar. It has been investigated such polarization characteristics: the amplitudes of the polarization matrix elements; an anisotropy coefficient; depolarization coefficient; asymmetry coefficient; the energy section was less than 1 dB at ranges up to 15 km and less than 1.5 dB at ranges up to 100 km. During the experiments urban objects and 6 various ships of small displacement having the closest values of the backscattering cross-section were used. The analysis has shown: the factor of the polarization selection for anisotropy objects and weather objects had the values about 0.02-0.08 Isotropy had the values of polarimetric correlation factor for hydrometers about 0.7-0.8, for earth surface about 0.8-0.9, for sea surface - from 0.33 to 0.7. The results of the work of recognition algorithm of a class 'concrete objects', and 'metal objects' are submitted as example in the paper. The result of experiments have shown that the probability of correct recognition of the identified objects was in the limits from 0.93 to 0.97.

  18. Action Recognition in a Crowded Environment

    PubMed Central

    Nieuwenhuis, Judith; Bülthoff, Isabelle; Barraclough, Nick; de la Rosa, Stephan

    2017-01-01

    So far, action recognition has been mainly examined with small point-light human stimuli presented alone within a narrow central area of the observer’s visual field. Yet, we need to recognize the actions of life-size humans viewed alone or surrounded by bystanders, whether they are seen in central or peripheral vision. Here, we examined the mechanisms in central vision and far periphery (40° eccentricity) involved in the recognition of the actions of a life-size actor (target) and their sensitivity to the presence of a crowd surrounding the target. In Experiment 1, we used an action adaptation paradigm to probe whether static or idly moving crowds might interfere with the recognition of a target’s action (hug or clap). We found that this type of crowds whose movements were dissimilar to the target action hardly affected action recognition in central and peripheral vision. In Experiment 2, we examined whether crowd actions that were more similar to the target actions affected action recognition. Indeed, the presence of that crowd diminished adaptation aftereffects in central vision as wells as in the periphery. We replicated Experiment 2 using a recognition task instead of an adaptation paradigm. With this task, we found evidence of decreased action recognition accuracy, but this was significant in peripheral vision only. Our results suggest that the presence of a crowd carrying out actions similar to that of the target affects its recognition. We outline how these results can be understood in terms of high-level crowding effects that operate on action-sensitive perceptual channels. PMID:29308177

  19. Structure and DNA-Binding Sites of the SWI1 AT-rich Interaction Domain (ARID) Suggest Determinants for Sequence-Specific DNA Recognition

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

    Kim, Suhkmann; Zhang, Ziming; Upchurch, Sean

    2004-04-16

    2 ARID is a homologous family of DNA-binding domains that occur in DNA binding proteins from a wide variety of species, ranging from yeast to nematodes, insects, mammals and plants. SWI1, a member of the SWI/SNF protein complex that is involved in chromatin remodeling during transcription, contains the ARID motif. The ARID domain of human SWI1 (also known as p270) does not select for a specific DNA sequence from a random sequence pool. The lack of sequence specificity shown by the SWI1 ARID domain stands in contrast to the other characterized ARID domains, which recognize specific AT-rich sequences. We havemore » solved the three-dimensional structure of human SWI1 ARID using solution NMR methods. In addition, we have characterized non-specific DNA-binding by the SWI1 ARID domain. Results from this study indicate that a flexible long internal loop in ARID motif is likely to be important for sequence specific DNA-recognition. The structure of human SWI1 ARID domain also represents a distinct structural subfamily. Studies of ARID indicate that boundary of the DNA binding structural and functional domains can extend beyond the sequence homologous region in a homologous family of proteins. Structural studies of homologous domains such as ARID family of DNA-binding domains should provide information to better predict the boundary of structural and functional domains in structural genomic studies. Key Words: ARID, SWI1, NMR, structural genomics, protein-DNA interaction.« less

  20. Target recognition for ladar range image using slice image

    NASA Astrophysics Data System (ADS)

    Xia, Wenze; Han, Shaokun; Wang, Liang

    2015-12-01

    A shape descriptor and a complete shape-based recognition system using slice images as geometric feature descriptor for ladar range images are introduced. A slice image is a two-dimensional image generated by three-dimensional Hough transform and the corresponding mathematical transformation. The system consists of two processes, the model library construction and recognition. In the model library construction process, a series of range images are obtained after the model object is sampled at preset attitude angles. Then, all the range images are converted into slice images. The number of slice images is reduced by clustering analysis and finding a representation to reduce the size of the model library. In the recognition process, the slice image of the scene is compared with the slice image in the model library. The recognition results depend on the comparison. Simulated ladar range images are used to analyze the recognition and misjudgment rates, and comparison between the slice image representation method and moment invariants representation method is performed. The experimental results show that whether in conditions without noise or with ladar noise, the system has a high recognition rate and low misjudgment rate. The comparison experiment demonstrates that the slice image has better representation ability than moment invariants.

  1. HMMerThread: detecting remote, functional conserved domains in entire genomes by combining relaxed sequence-database searches with fold recognition.

    PubMed

    Bradshaw, Charles Richard; Surendranath, Vineeth; Henschel, Robert; Mueller, Matthias Stefan; Habermann, Bianca Hermine

    2011-03-10

    Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs) are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ∼4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10), a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in proteins based on weak

  2. HMMerThread: Detecting Remote, Functional Conserved Domains in Entire Genomes by Combining Relaxed Sequence-Database Searches with Fold Recognition

    PubMed Central

    Bradshaw, Charles Richard; Surendranath, Vineeth; Henschel, Robert; Mueller, Matthias Stefan; Habermann, Bianca Hermine

    2011-01-01

    Conserved domains in proteins are one of the major sources of functional information for experimental design and genome-level annotation. Though search tools for conserved domain databases such as Hidden Markov Models (HMMs) are sensitive in detecting conserved domains in proteins when they share sufficient sequence similarity, they tend to miss more divergent family members, as they lack a reliable statistical framework for the detection of low sequence similarity. We have developed a greatly improved HMMerThread algorithm that can detect remotely conserved domains in highly divergent sequences. HMMerThread combines relaxed conserved domain searches with fold recognition to eliminate false positive, sequence-based identifications. With an accuracy of 90%, our software is able to automatically predict highly divergent members of conserved domain families with an associated 3-dimensional structure. We give additional confidence to our predictions by validation across species. We have run HMMerThread searches on eight proteomes including human and present a rich resource of remotely conserved domains, which adds significantly to the functional annotation of entire proteomes. We find ∼4500 cross-species validated, remotely conserved domain predictions in the human proteome alone. As an example, we find a DNA-binding domain in the C-terminal part of the A-kinase anchor protein 10 (AKAP10), a PKA adaptor that has been implicated in cardiac arrhythmias and premature cardiac death, which upon stress likely translocates from mitochondria to the nucleus/nucleolus. Based on our prediction, we propose that with this HLH-domain, AKAP10 is involved in the transcriptional control of stress response. Further remotely conserved domains we discuss are examples from areas such as sporulation, chromosome segregation and signalling during immune response. The HMMerThread algorithm is able to automatically detect the presence of remotely conserved domains in proteins based on weak

  3. Structure of the Get3 targeting factor in complex with its membrane protein cargo

    DOE PAGES

    Mateja, Agnieszka; Paduch, Marcin; Chang, Hsin-Yang; ...

    2015-03-06

    Tail-anchored (TA) proteins are a physiologically important class of membrane proteins targeted to the endoplasmic reticulum by the conserved guided-entry of TA proteins (GET) pathway. During transit, their hydrophobic transmembrane domains (TMDs) are chaperoned by the cytosolic targeting factor Get3, but the molecular nature of the functional Get3-TA protein targeting complex remains unknown. In this paper, we reconstituted the physiologic assembly pathway for a functional targeting complex and showed that it comprises a TA protein bound to a Get3 homodimer. Crystal structures of Get3 bound to different TA proteins showed an α-helical TMD occupying a hydrophobic groove that spans themore » Get3 homodimer. Finally, our data elucidate the mechanism of TA protein recognition and shielding by Get3 and suggest general principles of hydrophobic domain chaperoning by cellular targeting factors.« less

  4. Multivalent binding of formin-binding protein 21 (FBP21)-tandem-WW domains fosters protein recognition in the pre-spliceosome.

    PubMed

    Klippel, Stefan; Wieczorek, Marek; Schümann, Michael; Krause, Eberhard; Marg, Berenice; Seidel, Thorsten; Meyer, Tim; Knapp, Ernst-Walter; Freund, Christian

    2011-11-04

    The high abundance of repetitive but nonidentical proline-rich sequences in spliceosomal proteins raises the question of how these known interaction motifs recruit their interacting protein domains. Whereas complex formation of these adaptors with individual motifs has been studied in great detail, little is known about the binding mode of domains arranged in tandem repeats and long proline-rich sequences including multiple motifs. Here we studied the interaction of the two adjacent WW domains of spliceosomal protein FBP21 with several ligands of different lengths and composition to elucidate the hallmarks of multivalent binding for this class of recognition domains. First, we show that many of the proteins that define the cellular proteome interacting with FBP21-WW1-WW2 contain multiple proline-rich motifs. Among these is the newly identified binding partner SF3B4. Fluorescence resonance energy transfer (FRET) analysis reveals the tandem-WW domains of FBP21 to interact with splicing factor 3B4 (SF3B4) in nuclear speckles where splicing takes place. Isothermal titration calorimetry and NMR shows that the tandem arrangement of WW domains and the multivalency of the proline-rich ligands both contribute to affinity enhancement. However, ligand exchange remains fast compared with the NMR time scale. Surprisingly, a N-terminal spin label attached to a bivalent ligand induces NMR line broadening of signals corresponding to both WW domains of the FBP21-WW1-WW2 protein. This suggests that distinct orientations of the ligand contribute to a delocalized and semispecific binding mode that should facilitate search processes within the spliceosome.

  5. Non-canonical binding interactions of the RNA recognition motif (RRM) domains of P34 protein modulate binding within the 5S ribonucleoprotein particle (5S RNP)

    PubMed Central

    Kamina, Anyango D.; Williams, Noreen

    2017-01-01

    RNA binding proteins are involved in many aspects of RNA metabolism. In Trypanosoma brucei, our laboratory has identified two trypanosome-specific RNA binding proteins P34 and P37 that are involved in the maturation of the 60S subunit during ribosome biogenesis. These proteins are part of the T. brucei 5S ribonucleoprotein particle (5S RNP) and P34 binds to 5S ribosomal RNA (rRNA) and ribosomal protein L5 through its N-terminus and its RNA recognition motif (RRM) domains. We generated truncated P34 proteins to determine these domains’ interactions with 5S rRNA and L5. Our analyses demonstrate that RRM1 of P34 mediates the majority of binding with 5S rRNA and the N-terminus together with RRM1 contribute the most to binding with L5. We determined that the consensus ribonucleoprotein (RNP) 1 and 2 sequences, characteristic of canonical RRM domains, are not fully conserved in the RRM domains of P34. However, the aromatic amino acids previously described to mediate base stacking interactions with their RNA target are conserved in both of the RRM domains of P34. Surprisingly, mutation of these aromatic residues did not disrupt but instead enhanced 5S rRNA binding. However, we identified four arginine residues located in RRM1 of P34 that strongly impact L5 binding. These mutational analyses of P34 suggest that the binding site for 5S rRNA and L5 are near each other and specific residues within P34 regulate the formation of the 5S RNP. These studies show the unique way that the domains of P34 mediate binding with the T. brucei 5S RNP. PMID:28542332

  6. Target recognition based on the moment functions of radar signatures

    NASA Astrophysics Data System (ADS)

    Kim, Kyung-Tae; Kim, Hyo-Tae

    2002-03-01

    In this paper, we present the results of target recognition research based on the moment functions of various radar signatures, such as time-frequency signatures, range profiles, and scattering centers. The proposed approach utilizes geometrical moments or central moments of the obtained radar signatures. In particular, we derived exact and closed form expressions of the geometrical moments of the adaptive Gaussian representation (AGR), which is one of the adaptive joint time-frequency techniques, and also computed the central moments of range profiles and one-dimensional (1-D) scattering centers on a target, which are obtained by various super-resolution techniques. The obtained moment functions are further processed to provide small dimensional and redundancy-free feature vectors, and classified via a neural network approach or a Bayes classifier. The performances of the proposed technique are demonstrated using a simulated radar cross section (RCS) data set, or a measured RCS data set of various scaled aircraft models, obtained at the Pohang University of Science and Technology (POSTECH) compact range facility. Results show that the techniques in this paper can not only provide reliable classification accuracy, but also save computational resources.

  7. Structural basis underlying CAC RNA recognition by the RRM domain of dimeric RNA-binding protein RBPMS

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

    Teplova, Marianna; Farazi, Thalia A.; Tuschl, Thomas

    Abstract RNA-binding protein with multiple splicing (designated RBPMS) is a higher vertebrate mRNA-binding protein containing a single RNA recognition motif (RRM). RBPMS has been shown to be involved in mRNA transport, localization and stability, with key roles in axon guidance, smooth muscle plasticity, as well as regulation of cancer cell proliferation and migration. We report on structure-function studies of the RRM domain of RBPMS bound to a CAC-containing single-stranded RNA. These results provide insights into potential topologies of complexes formed by the RBPMS RRM domain and the tandem CAC repeat binding sites as detected by photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation. Thesemore » studies establish that the RRM domain of RBPMS forms a symmetrical dimer in the free state, with each monomer binding sequence-specifically to all three nucleotides of a CAC segment in the RNA bound state. Structure-guided mutations within the dimerization and RNA-binding interfaces of RBPMS RRM on RNA complex formation resulted in both disruption of dimerization and a decrease in RNA-binding affinity as observed by size exclusion chromatography and isothermal titration calorimetry. As anticipated from biochemical binding studies, over-expression of dimerization or RNA-binding mutants of Flag-HA-tagged RBPMS were no longer able to track with stress granules in HEK293 cells, thereby documenting the deleterious effects of such mutationsin vivo.« less

  8. A Pathogenic Nematode Targets Recognition Proteins to Avoid Insect Defenses

    PubMed Central

    Toubarro, Duarte; Avila, Mónica Martinez; Montiel, Rafael; Simões, Nelson

    2013-01-01

    Steinernema carpocapsae is a nematode pathogenic in a wide variety of insect species. The great pathogenicity of this nematode has been ascribed to its ability to overcome the host immune response; however, little is known about the mechanisms involved in this process. The analysis of an expressed sequence tags (EST) library in the nematode during the infective phase was performed and a highly abundant contig homologous to serine protease inhibitors was identified. In this work, we show that this contig is part of a 641-bp cDNA that encodes a BPTI-Kunitz family inhibitor (Sc-KU-4), which is up-regulated in the parasite during invasion and installation. Recombinant Sc-KU-4 protein was produced in Escherichia coli and shown to inhibit chymotrypsin and elastase activities in a dose-dependent manner by a competitive mechanism with Ki values of 1.8 nM and 2.6 nM, respectively. Sc-KU-4 also inhibited trypsin and thrombin activities to a lesser extent. Studies of the mode of action of Sc-KU-4 and its effects on insect defenses suggest that although Sc-KU-4 did not inhibit the activation of hemocytes or the formation of clotting fibers, it did inhibit hemocyte aggregation and the entrapment of foreign particles by fibers. Moreover, Sc-KU-4 avoided encapsulation and the deposition of clotting materials, which usually occurs in response to foreign particles. We show by protein-protein interaction that Sc-KU-4 targets recognition proteins of insect immune system such as masquerade-like and serine protease-like homologs. The interaction of Sc-KU-4 with these proteins explains the ability of the nematode to overcome host reactions and its large pathogenic spectrum, once these immune proteins are well conserved in insects. The discovery of this inhibitor targeting insect recognition proteins opens new avenues for the development of S . carpocapsae as a biological control agent and provides a new tool to study host-pathogen interactions. PMID:24098715

  9. Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum

    PubMed Central

    2012-01-01

    Background Hidden Markov Models (HMMs) are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such as P. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains. Results Using P. falciparum as an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD) procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values. Conclusion We show that the new approaches allow identification of several domain families previously absent in the P. falciparum proteome

  10. Fitting hidden Markov models of protein domains to a target species: application to Plasmodium falciparum.

    PubMed

    Terrapon, Nicolas; Gascuel, Olivier; Maréchal, Eric; Bréhélin, Laurent

    2012-05-01

    Hidden Markov Models (HMMs) are a powerful tool for protein domain identification. The Pfam database notably provides a large collection of HMMs which are widely used for the annotation of proteins in new sequenced organisms. In Pfam, each domain family is represented by a curated multiple sequence alignment from which a profile HMM is built. In spite of their high specificity, HMMs may lack sensitivity when searching for domains in divergent organisms. This is particularly the case for species with a biased amino-acid composition, such as P. falciparum, the main causal agent of human malaria. In this context, fitting HMMs to the specificities of the target proteome can help identify additional domains. Using P. falciparum as an example, we compare approaches that have been proposed for this problem, and present two alternative methods. Because previous attempts strongly rely on known domain occurrences in the target species or its close relatives, they mainly improve the detection of domains which belong to already identified families. Our methods learn global correction rules that adjust amino-acid distributions associated with the match states of HMMs. These rules are applied to all match states of the whole HMM library, thus enabling the detection of domains from previously absent families. Additionally, we propose a procedure to estimate the proportion of false positives among the newly discovered domains. Starting with the Pfam standard library, we build several new libraries with the different HMM-fitting approaches. These libraries are first used to detect new domain occurrences with low E-values. Second, by applying the Co-Occurrence Domain Discovery (CODD) procedure we have recently proposed, the libraries are further used to identify likely occurrences among potential domains with higher E-values. We show that the new approaches allow identification of several domain families previously absent in the P. falciparum proteome and the Apicomplexa phylum, and

  11. A Tail of Two Sites: A Bipartite Mechanism for Recognition of Notch Ligands by Mind Bomb E3 Ligases

    PubMed Central

    McMillan, Brian J.; Schnute, Björn; Ohlenhard, Nadja; Zimmerman, Brandon; Miles, Laura; Beglova, Natalia; Klein, Thomas; Blacklow, Stephen C.

    2015-01-01

    Summary Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. We present here crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membrane proximal region and the other near the C-terminus. Together, these studies provide new insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential new target for therapeutic modulation of Notch signal transduction in disease. PMID:25747658

  12. A Tail of Two Sites: A Bipartite Mechanism for Recognition of Notch Ligands by Mind Bomb E3 Ligases

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

    McMillan, Brian J.; Schnute, Björn; Ohlenhard, Nadja

    Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. Here we present crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membranemore » proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.« less

  13. A Tail of Two Sites: A Bipartite Mechanism for Recognition of Notch Ligands by Mind Bomb E3 Ligases

    DOE PAGES

    McMillan, Brian J.; Schnute, Björn; Ohlenhard, Nadja; ...

    2015-03-05

    Mind bomb (Mib) proteins are large, multi-domain E3 ligases that promote ubiquitination of the cytoplasmic tails of Notch ligands. This ubiquitination step marks the ligand proteins for epsin-dependent endocytosis, which is critical for in vivo Notch receptor activation. Here we present crystal structures of the substrate recognition domains of Mib1, both in isolation and in complex with peptides derived from Notch ligands. The structures, in combination with biochemical, cellular, and in vivo assays, show that Mib1 contains two independent substrate recognition domains that engage two distinct epitopes from the cytoplasmic tail of the ligand Jagged1, one in the intracellular membranemore » proximal region and the other near the C terminus. Together, these studies provide insights into the mechanism of ubiquitin transfer by Mind bomb E3 ligases, illuminate a key event in ligand-induced activation of Notch receptors, and identify a potential target for therapeutic modulation of Notch signal transduction in disease.« less

  14. Rsp5 WW domains interact directly with the carboxyl-terminal domain of RNA polymerase II.

    PubMed

    Chang, A; Cheang, S; Espanel, X; Sudol, M

    2000-07-07

    RSP5 is an essential gene in Saccharomyces cerevisiae and was recently shown to form a physical and functional complex with RNA polymerase II (RNA pol II). The amino-terminal half of Rsp5 consists of four domains: a C2 domain, which binds membrane phospholipids; and three WW domains, which are protein interaction modules that bind proline-rich ligands. The carboxyl-terminal half of Rsp5 contains a HECT (homologous to E6-AP carboxyl terminus) domain that catalytically ligates ubiquitin to proteins and functionally classifies Rsp5 as an E3 ubiquitin-protein ligase. The C2 and WW domains are presumed to act as membrane localization and substrate recognition modules, respectively. We report that the second (and possibly third) Rsp5 WW domain mediates binding to the carboxyl-terminal domain (CTD) of the RNA pol II large subunit. The CTD comprises a heptamer (YSPTSPS) repeated 26 times and a PXY core that is critical for interaction with a specific group of WW domains. An analysis of synthetic peptides revealed a minimal CTD sequence that is sufficient to bind to the second Rsp5 WW domain (Rsp5 WW2) in vitro and in yeast two-hybrid assays. Furthermore, we found that specific "imperfect" CTD repeats can form a complex with Rsp5 WW2. In addition, we have shown that phosphorylation of this minimal CTD sequence on serine, threonine and tyrosine residues acts as a negative regulator of the Rsp5 WW2-CTD interaction. In view of the recent data pertaining to phosphorylation-driven interactions between the RNA pol II CTD and the WW domain of Ess1/Pin1, we suggest that CTD dephosphorylation may be a prerequisite for targeted RNA pol II degradation.

  15. Modeling side-chains using molecular dynamics improve recognition of binding region in CAPRI targets.

    PubMed

    Camacho, Carlos J

    2005-08-01

    The CAPRI-II experiment added an extra level of complexity to the problem of predicting protein-protein interactions by including 5 targets for which participants had to build or complete the 3-dimensional (3D) structure of either the receptor or ligand based on the structure of a close homolog. In this article, we describe how modeling key side-chains using molecular dynamics (MD) in explicit solvent improved the recognition of the binding region of a free energy- based computational docking method. In particular, we show that MD is able to predict with relatively high accuracy the rotamer conformation of the anchor side-chains important for molecular recognition as suggested by Rajamani et al. (Proc Natl Acad Sci USA 2004;101:11287-11292). As expected, the conformations are some of the most common rotamers for the given residue, while latch side-chains that undergo induced fit upon binding are forced into less common conformations. Using these models as starting conformations in conjunction with the rigid-body docking server ClusPro and the flexible docking algorithm SmoothDock, we produced valuable predictions for 6 of the 9 targets in CAPRI-II, missing only the 3 targets that underwent significant structural rearrangements upon binding. We also show that our free energy- based scoring function, consisting of the sum of van der Waals, Coulombic electrostatic with a distance-dependent dielectric, and desolvation free energy successfully discriminates the nativelike conformation of our submitted predictions. The latter emphasizes the critical role that thermodynamics plays on our methodology, and validates the generality of the algorithm to predict protein interactions.

  16. Emotional recognition from dynamic facial, vocal and musical expressions following traumatic brain injury.

    PubMed

    Drapeau, Joanie; Gosselin, Nathalie; Peretz, Isabelle; McKerral, Michelle

    2017-01-01

    To assess emotion recognition from dynamic facial, vocal and musical expressions in sub-groups of adults with traumatic brain injuries (TBI) of different severities and identify possible common underlying mechanisms across domains. Forty-one adults participated in this study: 10 with moderate-severe TBI, nine with complicated mild TBI, 11 with uncomplicated mild TBI and 11 healthy controls, who were administered experimental (emotional recognition, valence-arousal) and control tasks (emotional and structural discrimination) for each domain. Recognition of fearful faces was significantly impaired in moderate-severe and in complicated mild TBI sub-groups, as compared to those with uncomplicated mild TBI and controls. Effect sizes were medium-large. Participants with lower GCS scores performed more poorly when recognizing fearful dynamic facial expressions. Emotion recognition from auditory domains was preserved following TBI, irrespective of severity. All groups performed equally on control tasks, indicating no perceptual disorders. Although emotional recognition from vocal and musical expressions was preserved, no correlation was found across auditory domains. This preliminary study may contribute to improving comprehension of emotional recognition following TBI. Future studies of larger samples could usefully include measures of functional impacts of recognition deficits for fearful facial expressions. These could help refine interventions for emotional recognition following a brain injury.

  17. Induced oligomerization targets Golgi proteins for degradation in lysosomes.

    PubMed

    Tewari, Ritika; Bachert, Collin; Linstedt, Adam D

    2015-12-01

    Manganese protects cells against forms of Shiga toxin by down-regulating the cycling Golgi protein GPP130. Down-regulation occurs when Mn binding causes GPP130 to oligomerize and traffic to lysosomes. To determine how GPP130 is redirected to lysosomes, we tested the role of GGA1 and clathrin, which mediate sorting in the canonical Golgi-to-lysosome pathway. GPP130 oligomerization was induced using either Mn or a self-interacting version of the FKBP domain. Inhibition of GGA1 or clathrin specifically blocked GPP130 redistribution, suggesting recognition of the aggregated GPP130 by the GGA1/clathrin-sorting complex. Unexpectedly, however, GPP130's cytoplasmic domain was not required, and redistribution also occurred after removal of GPP130 sequences needed for its normal cycling. Therefore, to test whether aggregate recognition might be a general phenomenon rather than one involving a specific GPP130 determinant, we induced homo-oligomerization of two unrelated Golgi-targeted constructs using the FKBP strategy. These were targeted to the cis- and trans-Golgi, respectively, using domains from mannosidase-1 and galactosyltransferase. Significantly, upon oligomerization, each redistributed to peripheral punctae and was degraded. This occurred in the absence of detectable UPR activation. These findings suggest the unexpected presence of quality control in the Golgi that recognizes aggregated Golgi proteins and targets them for degradation in lysosomes. © 2015 Tewari et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0).

  18. Perceptual fluency and affect without recognition.

    PubMed

    Anand, P; Sternthal, B

    1991-05-01

    A dichotic listening task was used to investigate the affect-without-recognition phenomenon. Subjects performed a distractor task by responding to the information presented in one ear while ignoring the target information presented in the other ear. The subjects' recognition of and affect toward the target information as well as toward foils was measured. The results offer evidence for the affect-without-recognition phenomenon. Furthermore, the data suggest that the subjects' affect toward the stimuli depended primarily on the extent to which the stimuli were perceived as familiar (i.e., subjective familiarity), and this perception was influenced by the ear in which the distractor or the target information was presented. These data are interpreted in terms of current models of recognition memory and hemispheric lateralization.

  19. TIA-1 RRM23 binding and recognition of target oligonucleotides

    PubMed Central

    Waris, Saboora; García-Mauriño, Sofía M.; Sivakumaran, Andrew; Beckham, Simone A.; Loughlin, Fionna E.; Gorospe, Myriam; Díaz-Moreno, Irene; Wilce, Matthew C.J.

    2017-01-01

    Abstract TIA-1 (T-cell restricted intracellular antigen-1) is an RNA-binding protein involved in splicing and translational repression. It mainly interacts with RNA via its second and third RNA recognition motifs (RRMs), with specificity for U-rich sequences directed by RRM2. It has recently been shown that RRM3 also contributes to binding, with preferential binding for C-rich sequences. Here we designed UC-rich and CU-rich 10-nt sequences for engagement of both RRM2 and RRM3 and demonstrated that the TIA-1 RRM23 construct preferentially binds the UC-rich RNA ligand (5΄-UUUUUACUCC-3΄). Interestingly, this binding depends on the presence of Lys274 that is C-terminal to RRM3 and binding to equivalent DNA sequences occurs with similar affinity. Small-angle X-ray scattering was used to demonstrate that, upon complex formation with target RNA or DNA, TIA-1 RRM23 adopts a compact structure, showing that both RRMs engage with the target 10-nt sequences to form the complex. We also report the crystal structure of TIA-1 RRM2 in complex with DNA to 2.3 Å resolution providing the first atomic resolution structure of any TIA protein RRM in complex with oligonucleotide. Together our data support a specific mode of TIA-1 RRM23 interaction with target oligonucleotides consistent with the role of TIA-1 in binding RNA to regulate gene expression. PMID:28184449

  20. A domain unique to plant RanGAP is responsible for its targeting to the plant nuclear rim

    PubMed Central

    Rose, Annkatrin; Meier, Iris

    2001-01-01

    Ran is a small signaling GTPase that is involved in nucleocytoplasmic transport. Two additional functions of animal Ran in the formation of spindle asters and the reassembly of the nuclear envelope in mitotic cells have been recently reported. In contrast to Ras or Rho, Ran is not associated with membranes. Instead, the spatial sequestering of its accessory proteins, the Ran GTPase-activating protein RanGAP and the nucleotide exchange factor RCC1, appears to define the local concentration of RanGTP vs. RanGDP involved in signaling. Mammalian RanGAP is bound to the nuclear pore by a mechanism involving the attachment of small ubiquitin-related modifier protein (SUMO) to its C terminus and the subsequent binding of the SUMOylated domain to the nucleoporin Nup358. Here we show that plant RanGAP utilizes a different mechanism for nuclear envelope association, involving a novel targeting domain that appears to be unique to plants. The N-terminal WPP domain is highly conserved among plant RanGAPs and the small, plant-specific nuclear envelope-associated protein MAF1, but not present in yeast or animal RanGAP. Confocal laser scanning microscopy of green fluorescent protein (GFP) fusion proteins showed that it is necessary for RanGAP targeting and sufficient to target the heterologous protein GFP to the plant nuclear rim. The highly conserved tryptophan and proline residues of the WPP motif are necessary for its function. The 110-aa WPP domain is the first nuclear-envelope targeting domain identified in plants. Its fundamental difference to its mammalian counterpart implies that different mechanisms have evolved in plants and animals to anchor RanGAP at the nuclear surface. PMID:11752475

  1. Finding Semirigid Domains in Biomolecules by Clustering Pair-Distance Variations

    PubMed Central

    Schreiner, Wolfgang

    2014-01-01

    Dynamic variations in the distances between pairs of atoms are used for clustering subdomains of biomolecules. We draw on a well-known target function for clustering and first show mathematically that the assignment of atoms to clusters has to be crisp, not fuzzy, as hitherto assumed. This reduces the computational load of clustering drastically, and we demonstrate results for several biomolecules relevant in immunoinformatics. Results are evaluated regarding the number of clusters, cluster size, cluster stability, and the evolution of clusters over time. Crisp clustering lends itself as an efficient tool to locate semirigid domains in the simulation of biomolecules. Such domains seem crucial for an optimum performance of subsequent statistical analyses, aiming at detecting minute motional patterns related to antigen recognition and signal transduction. PMID:24959586

  2. The structure and dynamics of tandem WW domains in a negative regulator of notch signaling, Suppressor of deltex.

    PubMed

    Fedoroff, Oleg Y; Townson, Sharon A; Golovanov, Alexander P; Baron, Martin; Avis, Johanna M

    2004-08-13

    WW domains mediate protein recognition, usually though binding to proline-rich sequences. In many proteins, WW domains occur in tandem arrays. Whether or how individual domains within such arrays cooperate to recognize biological partners is, as yet, poorly characterized. An important question is whether functional diversity of different WW domain proteins is reflected in the structural organization and ligand interaction mechanisms of their multiple domains. We have determined the solution structure and dynamics of a pair of WW domains (WW3-4) from a Drosophila Nedd4 family protein called Suppressor of deltex (Su(dx)), a regulator of Notch receptor signaling. We find that the binding of a type 1 PPPY ligand to WW3 stabilizes the structure with effects propagating to the WW4 domain, a domain that is not active for ligand binding. Both WW domains adopt the characteristic triple-stranded beta-sheet structure, and significantly, this is the first example of a WW domain structure to include a domain (WW4) lacking the second conserved Trp (replaced by Phe). The domains are connected by a flexible linker, which allows a hinge-like motion of domains that may be important for the recognition of functionally relevant targets. Our results contrast markedly with those of the only previously determined three-dimensional structure of tandem WW domains, that of the rigidly oriented WW domain pair from the RNA-splicing factor Prp40. Our data illustrate that arrays of WW domains can exhibit a variety of higher order structures and ligand interaction mechanisms.

  3. Research on application of LADAR in ground vehicle recognition

    NASA Astrophysics Data System (ADS)

    Lan, Jinhui; Shen, Zhuoxun

    2009-11-01

    For the requirement of many practical applications in the field of military, the research of 3D target recognition is active. The representation that captures the salient attributes of a 3D target independent of the viewing angle will be especially useful to the automatic 3D target recognition system. This paper presents a new approach of image generation based on Laser Detection and Ranging (LADAR) data. Range image of target is obtained by transformation of point cloud. In order to extract features of different ground vehicle targets and to recognize targets, zernike moment properties of typical ground vehicle targets are researched in this paper. A technique of support vector machine is applied to the classification and recognition of target. The new method of image generation and feature representation has been applied to the outdoor experiments. Through outdoor experiments, it can be proven that the method of image generation is stability, the moments are effective to be used as features for recognition, and the LADAR can be applied to the field of 3D target recognition.

  4. Toward More Accurate Iris Recognition Using Cross-Spectral Matching.

    PubMed

    Nalla, Pattabhi Ramaiah; Kumar, Ajay

    2017-01-01

    Iris recognition systems are increasingly deployed for large-scale applications such as national ID programs, which continue to acquire millions of iris images to establish identity among billions. However, with the availability of variety of iris sensors that are deployed for the iris imaging under different illumination/environment, significant performance degradation is expected while matching such iris images acquired under two different domains (either sensor-specific or wavelength-specific). This paper develops a domain adaptation framework to address this problem and introduces a new algorithm using Markov random fields model to significantly improve cross-domain iris recognition. The proposed domain adaptation framework based on the naive Bayes nearest neighbor classification uses a real-valued feature representation, which is capable of learning domain knowledge. Our approach to estimate corresponding visible iris patterns from the synthesis of iris patches in the near infrared iris images achieves outperforming results for the cross-spectral iris recognition. In this paper, a new class of bi-spectral iris recognition system that can simultaneously acquire visible and near infra-red images with pixel-to-pixel correspondences is proposed and evaluated. This paper presents experimental results from three publicly available databases; PolyU cross-spectral iris image database, IIITD CLI and UND database, and achieve outperforming results for the cross-sensor and cross-spectral iris matching.

  5. Haem Recognition By a Staphylococcus Aureus NEAT Domain

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

    Grigg, J.C.; Vermeiren, C.; Heinrichs, D.E.

    2009-06-01

    Successful pathogenic organisms have developed mechanisms to thrive under extreme levels of iron restriction. Haem-iron represents the largest iron reservoir in the human body and is a significant source of iron for some bacterial pathogens. NEAT (NEAr Transporter) domains are found exclusively in a family of cell surface proteins in Gram-positive bacteria. Many NEAT domain-containing proteins, including IsdA in Staphylococcus aureus, are implicated in haem binding. Here, we show that overexpression of IsdA in S. aureus enhances growth and an inactivation mutant of IsdA has a growth defect, compared with wild type, when grown in media containing haem as themore » sole iron source. Furthermore, the haem-binding property of IsdA is contained within the NEAT domain. Crystal structures of the apo-IsdA NEAT domain and in complex with haem were solved and reveal a clathrin adapter-like beta-sandwich fold with a large hydrophobic haem-binding pocket. Haem is bound with the propionate groups directed at the molecular surface and the iron is co-ordinated solely by Tyr(166). The phenol groups of Tyr(166) and Tyr(170) form an H-bond that may function in regulating haem binding and release. An analysis of IsdA structure-sequence alignments indicate that conservation of Tyr(166) is a predictor of haem binding by NEAT domains.« less

  6. Structural Basis for Telomerase RNA Recognition and RNP Assembly by the Holoenzyme La Family Protein p65

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

    Singh, Mahavir; Wang, Zhonghua; Koo, Bon-Kyung

    2012-07-01

    Telomerase is a ribonucleoprotein complex essential for maintenance of telomere DNA at linear chromosome ends. The catalytic core of Tetrahymena telomerase comprises a ternary complex of telomerase RNA (TER), telomerase reverse transcriptase (TERT), and the essential La family protein p65. NMR and crystal structures of p65 C-terminal domain and its complex with stem IV of TER reveal that RNA recognition is achieved by a combination of single- and double-stranded RNA binding, which induces a 105{sup o} bend in TER. The domain is a cryptic, atypical RNA recognition motif with a disordered C-terminal extension that forms an {alpha} helix in themore » complex necessary for hierarchical assembly of TERT with p65-TER. This work provides the first structural insight into biogenesis and assembly of TER with a telomerase-specific protein. Additionally, our studies define a structurally homologous domain (xRRM) in genuine La and LARP7 proteins and suggest a general mode of RNA binding for biogenesis of their diverse RNA targets.« less

  7. Digital signal processing algorithms for automatic voice recognition

    NASA Technical Reports Server (NTRS)

    Botros, Nazeih M.

    1987-01-01

    The current digital signal analysis algorithms are investigated that are implemented in automatic voice recognition algorithms. Automatic voice recognition means, the capability of a computer to recognize and interact with verbal commands. The digital signal is focused on, rather than the linguistic, analysis of speech signal. Several digital signal processing algorithms are available for voice recognition. Some of these algorithms are: Linear Predictive Coding (LPC), Short-time Fourier Analysis, and Cepstrum Analysis. Among these algorithms, the LPC is the most widely used. This algorithm has short execution time and do not require large memory storage. However, it has several limitations due to the assumptions used to develop it. The other 2 algorithms are frequency domain algorithms with not many assumptions, but they are not widely implemented or investigated. However, with the recent advances in the digital technology, namely signal processors, these 2 frequency domain algorithms may be investigated in order to implement them in voice recognition. This research is concerned with real time, microprocessor based recognition algorithms.

  8. Multivalent Binding of Formin-binding Protein 21 (FBP21)-Tandem-WW Domains Fosters Protein Recognition in the Pre-spliceosome*

    PubMed Central

    Klippel, Stefan; Wieczorek, Marek; Schümann, Michael; Krause, Eberhard; Marg, Berenice; Seidel, Thorsten; Meyer, Tim; Knapp, Ernst-Walter; Freund, Christian

    2011-01-01

    The high abundance of repetitive but nonidentical proline-rich sequences in spliceosomal proteins raises the question of how these known interaction motifs recruit their interacting protein domains. Whereas complex formation of these adaptors with individual motifs has been studied in great detail, little is known about the binding mode of domains arranged in tandem repeats and long proline-rich sequences including multiple motifs. Here we studied the interaction of the two adjacent WW domains of spliceosomal protein FBP21 with several ligands of different lengths and composition to elucidate the hallmarks of multivalent binding for this class of recognition domains. First, we show that many of the proteins that define the cellular proteome interacting with FBP21-WW1-WW2 contain multiple proline-rich motifs. Among these is the newly identified binding partner SF3B4. Fluorescence resonance energy transfer (FRET) analysis reveals the tandem-WW domains of FBP21 to interact with splicing factor 3B4 (SF3B4) in nuclear speckles where splicing takes place. Isothermal titration calorimetry and NMR shows that the tandem arrangement of WW domains and the multivalency of the proline-rich ligands both contribute to affinity enhancement. However, ligand exchange remains fast compared with the NMR time scale. Surprisingly, a N-terminal spin label attached to a bivalent ligand induces NMR line broadening of signals corresponding to both WW domains of the FBP21-WW1-WW2 protein. This suggests that distinct orientations of the ligand contribute to a delocalized and semispecific binding mode that should facilitate search processes within the spliceosome. PMID:21917930

  9. Target of Rapamycin Regulates Development and Ribosomal RNA Expression through Kinase Domain in Arabidopsis1[W][OA

    PubMed Central

    Ren, Maozhi; Qiu, Shuqing; Venglat, Prakash; Xiang, Daoquan; Feng, Li; Selvaraj, Gopalan; Datla, Raju

    2011-01-01

    Target of rapamycin (TOR) is a central regulator of cell growth, cell death, nutrition, starvation, hormone, and stress responses in diverse eukaryotes. However, very little is known about TOR signaling and the associated functional domains in plants. We have taken a genetic approach to dissect TOR functions in Arabidopsis (Arabidopsis thaliana) and report here that the kinase domain is essential for the role of TOR in embryogenesis and 45S rRNA expression. Twelve new T-DNA insertion mutants, spanning 14.2 kb of TOR-encoding genomic region, have been characterized. Nine of these share expression of defective kinase domain and embryo arrest at 16 to 32 cell stage. However, three T-DNA insertion lines affecting FATC domain displayed normal embryo development, indicating that FATC domain was dispensable in Arabidopsis. Genetic complementation showed that the TOR kinase domain alone in tor-10/tor-10 mutant background can rescue early embryo lethality and restore normal development. Overexpression of full-length TOR or kinase domain in Arabidopsis displayed developmental abnormalities in meristem, leaf, root, stem, flowering time, and senescence. We further show that TOR, especially the kinase domain, plays a role in ribosome biogenesis by activating 45S rRNA production. Of the six putative nuclear localization sequences in the kinase domain, nuclear localization sequence 6 was identified to confer TOR nuclear targeting in transient expression assays. Chromatin immunoprecipitation studies revealed that the HEAT repeat domain binds to 45S rRNA promoter and the 5′ external transcribed spacer elements motif. Together, these results show that TOR controls the embryogenesis, postembryonic development, and 45S rRNA production through its kinase domain in Arabidopsis. PMID:21266656

  10. In Silico Screening for Inhibitors of P-Glycoprotein That Target the Nucleotide Binding Domains

    PubMed Central

    Brewer, Frances K.; Follit, Courtney A.; Vogel, Pia D.

    2014-01-01

    Multidrug resistances and the failure of chemotherapies are often caused by the expression or overexpression of ATP-binding cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp). P-gp is expressed in the plasma membrane of many cell types and protects cells from accumulation of toxins. P-gp uses ATP hydrolysis to catalyze the transport of a broad range of mostly hydrophobic compounds across the plasma membrane and out of the cell. During cancer chemotherapy, the administration of therapeutics often selects for cells which overexpress P-gp, thereby creating populations of cancer cells resistant to a variety of chemically unrelated chemotherapeutics. The present study describes extremely high-throughput, massively parallel in silico ligand docking studies aimed at identifying reversible inhibitors of ATP hydrolysis that target the nucleotide-binding domains of P-gp. We used a structural model of human P-gp that we obtained from molecular dynamics experiments as the protein target for ligand docking. We employed a novel approach of subtractive docking experiments that identified ligands that bound predominantly to the nucleotide-binding domains but not the drug-binding domains of P-gp. Four compounds were found that inhibit ATP hydrolysis by P-gp. Using electron spin resonance spectroscopy, we showed that at least three of these compounds affected nucleotide binding to the transporter. These studies represent a successful proof of principle demonstrating the potential of targeted approaches for identifying specific inhibitors of P-gp. PMID:25270578

  11. Deficiency in chromosome congression by the inhibition of Plk1 polo box domain-dependent recognition.

    PubMed

    Watanabe, Nobumoto; Sekine, Tomomi; Takagi, Masatoshi; Iwasaki, Jun-ichi; Imamoto, Naoko; Kawasaki, Hisashi; Osada, Hiroyuki

    2009-01-23

    Polo-like kinase 1 (Plk1) is one of the key regulators of mitotic cell division. In addition to an N-terminal protein kinase catalytic domain, Plk1 possesses a phosphopeptide binding domain named polo box domain (PBD) at its C terminus. PBD is postulated to be essential for Plk1 localization and substrate targeting. Here, we developed a high-throughput screening system to identify inhibitors of PBD-dependent binding and screened a chemical library. We isolated a benzotropolone-containing natural compound derived from nutgalls (purpurogallin (PPG)) that inhibited PBD-dependent binding in vitro and in vivo. PPG not only delayed the onset of mitosis but also prolonged the progression of mitosis in HeLa cells. Although apparently normal bipolar spindles were formed even in the presence of PPG, the perturbation of chromosome alignment at metaphase plates activated the spindle assembly checkpoint pathway. These results demonstrate the predominant role of PBD-dependent binding on smooth chromosome congression at metaphase.

  12. Recognition mechanism of p63 by the E3 ligase Itch: novel strategy in the study and inhibition of this interaction.

    PubMed

    Bellomaria, Alessia; Barbato, Gaetano; Melino, Gerry; Paci, Maurizio; Melino, Sonia

    2012-10-01

    The HECT-containing E3 ubiquitin ligase Itch mediates the degradation of several proteins, including p63 and p73, involved in cell specification and fate. Itch contains four WW domains, which are essential for recognition on the target substrate, which contains a short proline-rich sequence. Several signaling complexes containing these domains have been associated with human diseases such as muscular dystrophy, Alzheimer's or Huntington's diseases. To gain further insight into the structural determinants of the Itch-WW2 domain, we investigated its interaction with p63. We assigned, by 3D heteronuclear NMR experiments, the backbone and side chains of the uniformly (13)C-(15)N-labeled Itch-WW2. In vitro interaction of Itch-WW2 domain with p63 was studied using its interactive p63 peptide, pep63. Pep63 is an 18-mer peptide corresponding to the region from 534-551 residue of p63, encompassing the PPxY motif that interacts with the Itch-WW domains, and we identified the residues involved in this molecular recognition. Moreover, here, a strategy of stabilization of the conformation of the PPxY peptide has been adopted, increasing the WW-ligand binding. We demonstrated that cyclization of pep63 leads to an increase of both the biological stability of the peptide and of the WW-ligand complex. Stable metal-binding complexes of the pep63 have been also obtained, and localized oxidative damage on Itch-WW2 domain has been induced, demonstrating the possibility of use of metal-pep63 complexes as models for the design of metal drugs to inhibit the Itch-WW-p63 recognition in vivo. Thus, our data suggest a novel strategy to study and inhibit the recognition mechanism of Itch E3-ligase.

  13. Infrared variation reduction by simultaneous background suppression and target contrast enhancement for deep convolutional neural network-based automatic target recognition

    NASA Astrophysics Data System (ADS)

    Kim, Sungho

    2017-06-01

    Automatic target recognition (ATR) is a traditionally challenging problem in military applications because of the wide range of infrared (IR) image variations and the limited number of training images. IR variations are caused by various three-dimensional target poses, noncooperative weather conditions (fog and rain), and difficult target acquisition environments. Recently, deep convolutional neural network-based approaches for RGB images (RGB-CNN) showed breakthrough performance in computer vision problems, such as object detection and classification. The direct use of RGB-CNN to the IR ATR problem fails to work because of the IR database problems (limited database size and IR image variations). An IR variation-reduced deep CNN (IVR-CNN) to cope with the problems is presented. The problem of limited IR database size is solved by a commercial thermal simulator (OKTAL-SE). The second problem of IR variations is mitigated by the proposed shifted ramp function-based intensity transformation. This can suppress the background and enhance the target contrast simultaneously. The experimental results on the synthesized IR images generated by the thermal simulator (OKTAL-SE) validated the feasibility of IVR-CNN for military ATR applications.

  14. Cooperative and selective roles of the WW domains of the yeast Nedd4-like ubiquitin ligase Rsp5 in the recognition of the arrestin-like adaptors Bul1 and Bul2.

    PubMed

    Watanabe, Daisuke; Murai, Hiroki; Tanahashi, Ryoya; Nakamura, Keishi; Sasaki, Toshiya; Takagi, Hiroshi

    The ubiquitin ligase Rsp5, which is the only yeast Saccharomyces cerevisiae member of the Nedd4-family, recognizes and ubiquitinates various substrate proteins through the functions of three conserved WW domains. To elucidate the role of each WW domain in endocytosis of the general amino acid permease Gap1 via interaction with the arrestin-like adaptor proteins Bul1 and Bul2 (Bul1/2), we investigated the effects of the double mutations that abrogate the recognition of PY motifs on target proteins (rsp5(W257F/P260A), rsp5(W359F/P362A), and rsp5(W415F/P418A)) and the alanine substitutions of the conserved threonine residues that are regarded as putative phosphorylation sites (rsp5(T255A), RSP5(T357A), and rsp5(T413A)), both of which are located within each WW domain. The rsp5(W257F/P260A), rsp5(W359F/P362A), and rsp5(W415F/P418A) mutations increased sensitivity to the proline analog azetidine-2-carboxylate (AZC), defective endocytosis of Gap1, and impaired interactions with Bul1. These results demonstrate that molecular recognition by each WW domain is responsible for the cooperative interaction with Bul1. Intriguingly, the RSP5(T357A) mutation enhanced AZC tolerance and endocytosis of Gap1, although rsp5(T255A) and rsp5(T413A) decreased both of them. While rsp5(T255A), RSP5(T357A), and rsp5(T413A) impaired the interaction of Rsp5 with Bul1, the RSP5(T357A) mutation specifically augmented the interaction with Bul2. The AZC tolerance enhanced by RSP5(T357A) was fully abolished by combining with each of the rsp5(W257F/P260A), rsp5(W359F/P362A), or rsp5(W415F/P418A) mutations. It was thus suggested that Thr357 in the WW2 domain has a unique role in preventing from the constitutive activation of Bul1/2-mediated endocytosis of Gap1. Taken together, our results highlight the cooperative and specific roles of WW domains in the regulation of Bul1/2-mediated cellular events. Copyright © 2015 Elsevier Inc. All rights reserved.

  15. OST-HTH: a novel predicted RNA-binding domain

    PubMed Central

    2010-01-01

    Background The mechanism by which the arthropod Oskar and vertebrate TDRD5/TDRD7 proteins nucleate or organize structurally related ribonucleoprotein (RNP) complexes, the polar granule and nuage, is poorly understood. Using sequence profile searches we identify a novel domain in these proteins that is widely conserved across eukaryotes and bacteria. Results Using contextual information from domain architectures, sequence-structure superpositions and available functional information we predict that this domain is likely to adopt the winged helix-turn-helix fold and bind RNA with a potential specificity for dsRNA. We show that in eukaryotes this domain is often combined in the same polypeptide with protein-protein- or lipid- interaction domains that might play a role in anchoring these proteins to specific cytoskeletal structures. Conclusions Thus, proteins with this domain might have a key role in the recognition and localization of dsRNA, including miRNAs, rasiRNAs and piRNAs hybridized to their targets. In other cases, this domain is fused to ubiquitin-binding, E3 ligase and ubiquitin-like domains indicating a previously under-appreciated role for ubiquitination in regulating the assembly and stability of nuage-like RNP complexes. Both bacteria and eukaryotes encode a conserved family of proteins that combines this predicted RNA-binding domain with a previously uncharacterized domain (DUF88). We present evidence that it is an RNAse belonging to the superfamily that includes the 5'->3' nucleases, PIN and NYN domains and might be recruited to degrade certain RNAs. Reviewers This article was reviewed by Sandor Pongor and Arcady Mushegian. PMID:20302647

  16. Programmable and multiparameter DNA-based logic platform for cancer recognition and targeted therapy.

    PubMed

    You, Mingxu; Zhu, Guizhi; Chen, Tao; Donovan, Michael J; Tan, Weihong

    2015-01-21

    The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy.

  17. Programmable and Multiparameter DNA-Based Logic Platform For Cancer Recognition and Targeted Therapy

    PubMed Central

    2014-01-01

    The specific inventory of molecules on diseased cell surfaces (e.g., cancer cells) provides clinicians an opportunity for accurate diagnosis and intervention. With the discovery of panels of cancer markers, carrying out analyses of multiple cell-surface markers is conceivable. As a trial to accomplish this, we have recently designed a DNA-based device that is capable of performing autonomous logic-based analysis of two or three cancer cell-surface markers. Combining the specific target-recognition properties of DNA aptamers with toehold-mediated strand displacement reactions, multicellular marker-based cancer analysis can be realized based on modular AND, OR, and NOT Boolean logic gates. Specifically, we report here a general approach for assembling these modular logic gates to execute programmable and higher-order profiling of multiple coexisting cell-surface markers, including several found on cancer cells, with the capacity to report a diagnostic signal and/or deliver targeted photodynamic therapy. The success of this strategy demonstrates the potential of DNA nanotechnology in facilitating targeted disease diagnosis and effective therapy. PMID:25361164

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

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

  19. Enhancement of Ebola Virus Infection via Ficolin-1 Interaction with the Mucin Domain of GP Glycoprotein.

    PubMed

    Favier, Anne-Laure; Gout, Evelyne; Reynard, Olivier; Ferraris, Olivier; Kleman, Jean-Philippe; Volchkov, Viktor; Peyrefitte, Christophe; Thielens, Nicole M

    2016-06-01

    Ebola virus infection requires the surface viral glycoprotein to initiate entry into the target cells. The trimeric glycoprotein is a highly glycosylated viral protein which has been shown to interact with host C-type lectin receptors and the soluble complement recognition protein mannose-binding lectin, thereby enhancing viral infection. Similarly to mannose-binding lectin, ficolins are soluble effectors of the innate immune system that recognize particular glycans at the pathogen surface. In this study, we demonstrate that ficolin-1 interacts with the Zaire Ebola virus (EBOV) glycoprotein, and we characterized this interaction by surface plasmon resonance spectroscopy. Ficolin-1 was shown to bind to the viral glycoprotein with a high affinity. This interaction was mediated by the fibrinogen-like recognition domain of ficolin-1 and the mucin-like domain of the viral glycoprotein. Using a ficolin-1 control mutant devoid of sialic acid-binding capacity, we identified sialylated moieties of the mucin domain to be potential ligands on the glycoprotein. In cell culture, using both pseudotyped viruses and EBOV, ficolin-1 was shown to enhance EBOV infection independently of the serum complement. We also observed that ficolin-1 enhanced EBOV infection on human monocyte-derived macrophages, described to be major viral target cells,. Competition experiments suggested that although ficolin-1 and mannose-binding lectin recognized different carbohydrate moieties on the EBOV glycoprotein, the observed enhancement of the infection likely depended on a common cellular receptor/partner. In conclusion, ficolin-1 could provide an alternative receptor-mediated mechanism for enhancing EBOV infection, thereby contributing to viral subversion of the host innate immune system. A specific interaction involving ficolin-1 (M-ficolin), a soluble effector of the innate immune response, and the glycoprotein (GP) of EBOV was identified. Ficolin-1 enhanced virus infection instead of tipping the

  20. Spatial location of neutralizing and non-neutralizing B cell epitopes on domain 1 of ricin toxin's binding subunit.

    PubMed

    Rong, Yinghui; Van Slyke, Greta; Vance, David J; Westfall, Jennifer; Ehrbar, Dylan; Mantis, Nicholas J

    2017-01-01

    Ricin toxin's binding subunit (RTB) is a galactose-/N-acetylgalactosamine (Gal/GalNac)-specific lectin that mediates uptake and intracellular trafficking of ricin within mammalian cells. Structurally, RTB consists of two globular domains, each divided into three homologous sub-domains (α, β, γ). In this report, we describe five new murine IgG monoclonal antibodies (mAbs) against RTB: MH3, 8A1, 8B3, LF1, and LC5. The mAbs have similar binding affinities (KD) for ricin holotoxin, but displayed a wide range of in vitro toxin-neutralizing activities. Competition ELISAs indicate that the two most potent toxin-neutralizing mAbs (MH3, 8A1), as well as one of the moderate toxin-neutralizing mAbs (LF1), recognize distinct epitopes near the low affinity Gal recognition domain in RTB subdomain 1α. Evaluated in a mouse model of systemic ricin challenge, all five mAbs afforded some benefit against intoxication, but only MH3 was protective. However, neither MH3 nor 24B11, another well-characterized mAb against RTB subdomain 1α, could passively protect mice against a mucosal (intranasal) ricin challenge. This is in contrast to SylH3, a previously characterized mAb directed against an epitope near RTB's high affinity Gal/GalNac recognition element in sub-domain 2γ, which protected animals against systemic and mucosal ricin exposure. SylH3 was significantly more effective than MH3 and 24B11 at blocking ricin attachment to host cell receptors, suggesting that mucosal immunity to ricin is best imparted by antibodies that target RTB's high affinity Gal/GalNac recognition element in subdomain 2γ, not the low affinity Gal recognition domain in subdomain 1α.

  1. TIA-1 RRM23 binding and recognition of target oligonucleotides.

    PubMed

    Waris, Saboora; García-Mauriño, Sofía M; Sivakumaran, Andrew; Beckham, Simone A; Loughlin, Fionna E; Gorospe, Myriam; Díaz-Moreno, Irene; Wilce, Matthew C J; Wilce, Jacqueline A

    2017-05-05

    TIA-1 (T-cell restricted intracellular antigen-1) is an RNA-binding protein involved in splicing and translational repression. It mainly interacts with RNA via its second and third RNA recognition motifs (RRMs), with specificity for U-rich sequences directed by RRM2. It has recently been shown that RRM3 also contributes to binding, with preferential binding for C-rich sequences. Here we designed UC-rich and CU-rich 10-nt sequences for engagement of both RRM2 and RRM3 and demonstrated that the TIA-1 RRM23 construct preferentially binds the UC-rich RNA ligand (5΄-UUUUUACUCC-3΄). Interestingly, this binding depends on the presence of Lys274 that is C-terminal to RRM3 and binding to equivalent DNA sequences occurs with similar affinity. Small-angle X-ray scattering was used to demonstrate that, upon complex formation with target RNA or DNA, TIA-1 RRM23 adopts a compact structure, showing that both RRMs engage with the target 10-nt sequences to form the complex. We also report the crystal structure of TIA-1 RRM2 in complex with DNA to 2.3 Å resolution providing the first atomic resolution structure of any TIA protein RRM in complex with oligonucleotide. Together our data support a specific mode of TIA-1 RRM23 interaction with target oligonucleotides consistent with the role of TIA-1 in binding RNA to regulate gene expression. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  2. Assessing the performance of a covert automatic target recognition algorithm

    NASA Astrophysics Data System (ADS)

    Ehrman, Lisa M.; Lanterman, Aaron D.

    2005-05-01

    Passive radar systems exploit illuminators of opportunity, such as TV and FM radio, to illuminate potential targets. Doing so allows them to operate covertly and inexpensively. Our research seeks to enhance passive radar systems by adding automatic target recognition (ATR) capabilities. In previous papers we proposed conducting ATR by comparing the radar cross section (RCS) of aircraft detected by a passive radar system to the precomputed RCS of aircraft in the target class. To effectively model the low-frequency setting, the comparison is made via a Rician likelihood model. Monte Carlo simulations indicate that the approach is viable. This paper builds on that work by developing a method for quickly assessing the potential performance of the ATR algorithm without using exhaustive Monte Carlo trials. This method exploits the relation between the probability of error in a binary hypothesis test under the Bayesian framework to the Chernoff information. Since the data are well-modeled as Rician, we begin by deriving a closed-form approximation for the Chernoff information between two Rician densities. This leads to an approximation for the probability of error in the classification algorithm that is a function of the number of available measurements. We conclude with an application that would be particularly cumbersome to accomplish via Monte Carlo trials, but that can be quickly addressed using the Chernoff information approach. This application evaluates the length of time that an aircraft must be tracked before the probability of error in the ATR algorithm drops below a desired threshold.

  3. Structural biology of antibody recognition of carbohydrate epitopes and potential uses for targeted cancer immunotherapies.

    PubMed

    Dingjan, Tamir; Spendlove, Ian; Durrant, Lindy G; Scott, Andrew M; Yuriev, Elizabeth; Ramsland, Paul A

    2015-10-01

    Monoclonal antibodies represent the most successful class of biopharmaceuticals for the treatment of cancer. Mechanisms of action of therapeutic antibodies are very diverse and reflect their ability to engage in antibody-dependent effector mechanisms, internalize to deliver cytotoxic payloads, and display direct effects on cells by lysis or by modulating the biological pathways of their target antigens. Importantly, one of the universal changes in cancer is glycosylation and carbohydrate-binding antibodies can be produced to selectively recognize tumor cells over normal tissues. A promising group of cell surface antibody targets consists of carbohydrates presented as glycolipids or glycoproteins. In this review, we outline the basic principles of antibody-based targeting of carbohydrate antigens in cancer. We also present a detailed structural view of antibody recognition and the conformational properties of a series of related tissue-blood group (Lewis) carbohydrates that are being pursued as potential targets of cancer immunotherapy. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. The GRP1 PH domain, like the AKT1 PH domain, possesses a sentry glutamate residue essential for specific targeting to plasma membrane PI(3,4,5)P(3).

    PubMed

    Pilling, Carissa; Landgraf, Kyle E; Falke, Joseph J

    2011-11-15

    During the appearance of the signaling lipid PI(3,4,5)P(3), an important subset of pleckstrin homology (PH) domains target signaling proteins to the plasma membrane. To ensure proper pathway regulation, such PI(3,4,5)P(3)-specific PH domains must exclude the more prevalant, constitutive plasma membrane lipid PI(4,5)P(2) and bind the rare PI(3,4,5)P(3) target lipid with sufficiently high affinity. Our previous study of the E17K mutant of the protein kinase B (AKT1) PH domain, together with evidence from Carpten et al. [Carpten, J. D., et al. (2007) Nature 448, 439-444], revealed that the native AKT1 E17 residue serves as a sentry glutamate that excludes PI(4,5)P(2), thereby playing an essential role in specific PI(3,4,5)P(3) targeting [Landgraf, K. E., et al. (2008) Biochemistry 47, 12260-12269]. The sentry glutamate hypothesis proposes that an analogous sentry glutamate residue is a widespread feature of PI(3,4,5)P(3)-specific PH domains, and that charge reversal mutation at the sentry glutamate position will yield both increased PI(4,5)P(2) affinity and constitutive plasma membrane targeting. To test this hypothesis, we investigated the E345 residue, a putative sentry glutamate, of the general receptor for phosphoinositides 1 (GRP1) PH domain. The results show that incorporation of the E345K charge reversal mutation into the GRP1 PH domain enhances PI(4,5)P(2) affinity 8-fold and yields constitutive plasma membrane targeting in cells, reminiscent of the effects of the E17K mutation in the AKT1 PH domain. Hydrolysis of plasma membrane PI(4,5)P(2) releases the E345K GRP1 PH domain into the cytoplasm, and the efficiency of this release increases when Arf6 binding is disrupted. Overall, the findings provide strong support for the sentry glutamate hypothesis and suggest that the GRP1 E345K mutation will be linked to changes in cell physiology and human pathologies, as demonstrated for AKT1 E17K [Carpten, J. D., et al. (2007) Nature 448, 439-444; Lindhurst, M. J., et al

  5. Strategies of targeting the extracellular domain of RON tyrosine kinase receptor for cancer therapy and drug delivery.

    PubMed

    Zarei, Omid; Benvenuti, Silvia; Ustun-Alkan, Fulya; Hamzeh-Mivehroud, Maryam; Dastmalchi, Siavoush

    2016-12-01

    Cancer is one of the most important life-threatening diseases in the world. The current efforts to combat cancer are being focused on molecular-targeted therapies. The main purpose of such approaches is based on targeting cancer cell-specific molecules to minimize toxicity for the normal cells. RON (Recepteur d'Origine Nantais) tyrosine kinase receptor is one of the promising targets in cancer-targeted therapy and drug delivery. In this review, we will summarize the available agents against extracellular domain of RON with potential antitumor activities. The presented antibodies and antibody drug conjugates against RON in this review showed wide spectrum of in vitro and in vivo antitumor activities promising the hope for them entering the clinical trials. Due to critical role of extracellular domain of RON in receptor activation, the development of therapeutic agents against this region could lead to fruitful outcome in cancer therapy.

  6. New partner proteins containing novel internal recognition motif for human Glutaminase Interacting Protein (hGIP)

    PubMed Central

    Zencir, Sevil; Banerjee, Monimoy; Dobson, Melanie J.; Ayaydin, Ferhan; Fodor, Elfrieda Ayaydin; Topcu, Zeki; Mohanty, Smita

    2013-01-01

    Regulation of gene expression in cells is mediated by protein-protein, DNA-protein and receptor-ligand interactions. PDZ (PSD-95/Discs-large/ZO-1) domains are protein–protein interaction modules. PDZ-containing proteins function in the organization of multi-protein complexes controlling spatial and temporal fidelity of intracellular signaling pathways. In general, PDZ proteins possess multiple domains facilitating distinct interactions. The human Glutaminase Interacting Protein (hGIP) is an unusual PDZ protein comprising entirely of a single PDZ domain and plays pivotal roles in many cellular processes through its interaction with the C-terminus of partner proteins. Here, we report the identification by yeast two-hybrid screening of two new hGIP-interacting partners, DTX1 and STAU1. Both proteins lack the typical C-terminal PDZ recognition motif but contain a novel internal hGIP recognition motif recently identified in a phage display library screen. Fluorescence resonance energy transfer and confocal microscopy analysis confirmed the in vivo association of hGIP with DTX1 and STAU1 in mammalian cells validating the previous discovery of S/T-X-V/L-D as a consensus internal motif for hGIP recognition. Similar to hGIP, DTX1 and STAU1 have been implicated in neuronal function. Identification of these new interacting partners furthers our understanding of GIP-regulated signaling cascades and these interactions may represent potential new drug targets in humans. PMID:23395680

  7. Loop nucleotides control primary and mature miRNA function in target recognition and repression

    PubMed Central

    Yue, Si-Biao; Deis Trujillo, Robin; Tang, Yujie; O'Gorman, William E

    2011-01-01

    MicroRNA (miRNA) genes produce three major RNA products; primary (pri-), precursor (pre-), and mature miRNAs. Each product includes sequences complementary to cognate targets, thus they all can in principle interact with the targets. In a recent study we showed that pri-miRNAs play a direct role in target recognition and repression in the absence of functional mature miRNAs. Here we examined the functional contribution of pri-miRNAs in target regulation when full-length functional miRNAs are present. We found that pri-let-7 loop nucleotides control the production of the 5′ end of mature miRNAs and modulate the activity of the miRNA gene. This insight enabled us to modulate biogenesis of functional mature miRNAs and dissect the causal relationships between mature miRNA biogenesis and target repression. We demonstrate that both pri- and mature miRNAs can contribute to target repression and that their contributions can be distinguished by the differences between the pri- and mature miRNAs' sensitivity to bind to the first seed nucleotide. Our results demonstrate that the regulatory information encoded in the pri-/pre-miRNA loop nucleotides controls the activities of pri-miRNAs and mature let-7 by influencing pri-miRNA and target complex formation and the fidelity of mature miRNA seed generation. PMID:22142974

  8. In silico screening for inhibitors of p-glycoprotein that target the nucleotide binding domains.

    PubMed

    Brewer, Frances K; Follit, Courtney A; Vogel, Pia D; Wise, John G

    2014-12-01

    Multidrug resistances and the failure of chemotherapies are often caused by the expression or overexpression of ATP-binding cassette transporter proteins such as the multidrug resistance protein, P-glycoprotein (P-gp). P-gp is expressed in the plasma membrane of many cell types and protects cells from accumulation of toxins. P-gp uses ATP hydrolysis to catalyze the transport of a broad range of mostly hydrophobic compounds across the plasma membrane and out of the cell. During cancer chemotherapy, the administration of therapeutics often selects for cells which overexpress P-gp, thereby creating populations of cancer cells resistant to a variety of chemically unrelated chemotherapeutics. The present study describes extremely high-throughput, massively parallel in silico ligand docking studies aimed at identifying reversible inhibitors of ATP hydrolysis that target the nucleotide-binding domains of P-gp. We used a structural model of human P-gp that we obtained from molecular dynamics experiments as the protein target for ligand docking. We employed a novel approach of subtractive docking experiments that identified ligands that bound predominantly to the nucleotide-binding domains but not the drug-binding domains of P-gp. Four compounds were found that inhibit ATP hydrolysis by P-gp. Using electron spin resonance spectroscopy, we showed that at least three of these compounds affected nucleotide binding to the transporter. These studies represent a successful proof of principle demonstrating the potential of targeted approaches for identifying specific inhibitors of P-gp. Copyright © 2014 by The American Society for Pharmacology and Experimental Therapeutics.

  9. Increase in Speech Recognition due to Linguistic Mismatch Between Target and Masker Speech: Monolingual and Simultaneous Bilingual Performance

    PubMed Central

    Calandruccio, Lauren; Zhou, Haibo

    2014-01-01

    Purpose To examine whether improved speech recognition during linguistically mismatched target–masker experiments is due to linguistic unfamiliarity of the masker speech or linguistic dissimilarity between the target and masker speech. Method Monolingual English speakers (n = 20) and English–Greek simultaneous bilinguals (n = 20) listened to English sentences in the presence of competing English and Greek speech. Data were analyzed using mixed-effects regression models to determine differences in English recogition performance between the 2 groups and 2 masker conditions. Results Results indicated that English sentence recognition for monolinguals and simultaneous English–Greek bilinguals improved when the masker speech changed from competing English to competing Greek speech. Conclusion The improvement in speech recognition that has been observed for linguistically mismatched target–masker experiments cannot be simply explained by the masker language being linguistically unknown or unfamiliar to the listeners. Listeners can improve their speech recognition in linguistically mismatched target–masker experiments even when the listener is able to obtain meaningful linguistic information from the masker speech. PMID:24167230

  10. ICPR-2016 - International Conference on Pattern Recognition

    Science.gov Websites

    Learning for Scene Understanding" Speakers ICPR2016 PAPER AWARDS Best Piero Zamperoni Student Paper -Paced Dictionary Learning for Cross-Domain Retrieval and Recognition Xu, Dan; Song, Jingkuan; Alameda discussions on recent advances in the fields of Pattern Recognition, Machine Learning and Computer Vision, and

  11. Molecular recognition of glyconanoparticles by RCA and E. coli K88 - designing transports for targeted therapy.

    PubMed

    Gallegos-Tabanico, Amed; Sarabia-Sainz, Jose A; Sarabia-Sainz, H Manuel; Carrillo Torres, Roberto; Guzman-Partida, Ana M; Monfort, Gabriela Ramos-Clamont; Silva-Campa, Erika; Burgara-Estrella, Alexel J; Angulo-Molina, Aracely; Acosta-Elias, Mónica; Pedroza-Montero, Martín; Vazquez-Moreno, Luz

    2017-01-01

    The targeted drug delivery has been studied as one of the main methods in medicine to ensure successful treatments of diseases. Pharmaceutical sciences are using micro or nano carriers to obtain a controlled delivery of drugs, able to selectively interact with pathogens, cells or tissues. In this work, we modified bovine serum albumin (BSA) with lactose, obtaining a neoglycan (BSA-Lac). Subsequently, we synthesized glyconanoparticles (NPBSA-Lac) with the premise that it would be recognized by microbial galactose specific lectins. NPBSA-Lac were tested for bio-recognition with adhesins of E. coli K88 and Ricinus communis agglutinin I (RCA). Glycation of BSA with lactose was analyzed by electrophoresis, infrared spectroscopy and fluorescence. Approximately 41 lactoses per BSA molecule were estimated. Nanoparticles were obtained using water in oil emulsion method and spheroid morphology with a range size of 300-500 nm was observed. Specific recognition of NPBSA-Lac by RCA and E. coli K88 was displayed by aggregation of nanoparticles analyzed by dynamic light scattering and atomic force microscopy. The results indicate that the lactosylated nanovectors could be targeted at the E. coli K88 adhesin and potentially could be used as a transporter for an antibacterial drug.

  12. Spatial location of neutralizing and non-neutralizing B cell epitopes on domain 1 of ricin toxin’s binding subunit

    PubMed Central

    Rong, Yinghui; Van Slyke, Greta; Vance, David J.; Westfall, Jennifer; Ehrbar, Dylan

    2017-01-01

    Ricin toxin’s binding subunit (RTB) is a galactose-/N-acetylgalactosamine (Gal/GalNac)-specific lectin that mediates uptake and intracellular trafficking of ricin within mammalian cells. Structurally, RTB consists of two globular domains, each divided into three homologous sub-domains (α, β, γ). In this report, we describe five new murine IgG monoclonal antibodies (mAbs) against RTB: MH3, 8A1, 8B3, LF1, and LC5. The mAbs have similar binding affinities (KD) for ricin holotoxin, but displayed a wide range of in vitro toxin-neutralizing activities. Competition ELISAs indicate that the two most potent toxin-neutralizing mAbs (MH3, 8A1), as well as one of the moderate toxin-neutralizing mAbs (LF1), recognize distinct epitopes near the low affinity Gal recognition domain in RTB subdomain 1α. Evaluated in a mouse model of systemic ricin challenge, all five mAbs afforded some benefit against intoxication, but only MH3 was protective. However, neither MH3 nor 24B11, another well-characterized mAb against RTB subdomain 1α, could passively protect mice against a mucosal (intranasal) ricin challenge. This is in contrast to SylH3, a previously characterized mAb directed against an epitope near RTB’s high affinity Gal/GalNac recognition element in sub-domain 2γ, which protected animals against systemic and mucosal ricin exposure. SylH3 was significantly more effective than MH3 and 24B11 at blocking ricin attachment to host cell receptors, suggesting that mucosal immunity to ricin is best imparted by antibodies that target RTB’s high affinity Gal/GalNac recognition element in subdomain 2γ, not the low affinity Gal recognition domain in subdomain 1α. PMID:28700745

  13. Peptides derived from human galectin-3 N-terminal tail interact with its carbohydrate recognition domain in a phosphorylation-dependent manner

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

    Berbís, M. Álvaro; André, Sabine; Cañada, F. Javier

    2014-01-03

    Highlights: •Galectin-3 is composed of a carbohydrate recognition domain and an N-terminal tail. •Synthetic peptides derived from the tail are shown to interact with the CRD. •This interaction is modulated by Ser- and Tyr-phosphorylation of the peptides. -- Abstract: Galectin-3 (Gal-3) is a multi-functional effector protein that functions in the cytoplasm and the nucleus, as well as extracellularly following non-classical secretion. Structurally, Gal-3 is unique among galectins with its carbohydrate recognition domain (CRD) attached to a rather long N-terminal tail composed mostly of collagen-like repeats (nine in the human protein) and terminating in a short non-collagenous terminal peptide sequence uniquemore » in this lectin family and not yet fully explored. Although several Ser and Tyr sites within the N-terminal tail can be phosphorylated, the physiological significance of this post-translational modification remains unclear. Here, we used a series of synthetic (phospho)peptides derived from the tail to assess phosphorylation-mediated interactions with {sup 15}N-labeled Gal-3 CRD. HSQC-derived chemical shift perturbations revealed selective interactions at the backface of the CRD that were attenuated by phosphorylation of Tyr 107 and Tyr 118, while phosphorylation of Ser 6 and Ser 12 was essential. Controls with sequence scrambling underscored inherent specificity. Our studies shed light on how phosphorylation of the N-terminal tail may impact on Gal-3 function and prompt further studies using phosphorylated full-length protein.« less

  14. Sparse and redundant representations for inverse problems and recognition

    NASA Astrophysics Data System (ADS)

    Patel, Vishal M.

    Sparse and redundant representation of data enables the description of signals as linear combinations of a few atoms from a dictionary. In this dissertation, we study applications of sparse and redundant representations in inverse problems and object recognition. Furthermore, we propose two novel imaging modalities based on the recently introduced theory of Compressed Sensing (CS). This dissertation consists of four major parts. In the first part of the dissertation, we study a new type of deconvolution algorithm that is based on estimating the image from a shearlet decomposition. Shearlets provide a multi-directional and multi-scale decomposition that has been mathematically shown to represent distributed discontinuities such as edges better than traditional wavelets. We develop a deconvolution algorithm that allows for the approximation inversion operator to be controlled on a multi-scale and multi-directional basis. Furthermore, we develop a method for the automatic determination of the threshold values for the noise shrinkage for each scale and direction without explicit knowledge of the noise variance using a generalized cross validation method. In the second part of the dissertation, we study a reconstruction method that recovers highly undersampled images assumed to have a sparse representation in a gradient domain by using partial measurement samples that are collected in the Fourier domain. Our method makes use of a robust generalized Poisson solver that greatly aids in achieving a significantly improved performance over similar proposed methods. We will demonstrate by experiments that this new technique is more flexible to work with either random or restricted sampling scenarios better than its competitors. In the third part of the dissertation, we introduce a novel Synthetic Aperture Radar (SAR) imaging modality which can provide a high resolution map of the spatial distribution of targets and terrain using a significantly reduced number of needed

  15. Impact of surfactants on the target recognition of Fab-conjugated PLGA nanoparticles.

    PubMed

    Kennedy, Patrick J; Perreira, Ines; Ferreira, Daniel; Nestor, Marika; Oliveira, Carla; Granja, Pedro L; Sarmento, Bruno

    2018-06-01

    Targeted drug delivery with nanoparticles (NPs) requires proper surface ligand presentation and availability. Surfactants are often used as stabilizers in the production of targeted NPs. Here, we evaluated the impact of surfactants on ligand functionalization and downstream molecular recognition. Our model system consisted of fluorescent poly(lactic-co-glycolic acid) (PLGA) NPs that were nanoprecipitated in one of a small panel of commonly-used surfactants followed by equivalent washes and conjugation of an engineered Fab antibody fragment. Size, polydispersity index and zeta potential were determined by dynamic light scattering and laser Doppler anemometry, and Fab presence on the NPs was assessed by enzyme-linked immunosorbent assay. Most importantly, Fab-decorated NP binding to the cell surface receptor was monitored by fluorescence-activated cell sorting. 2% polyvinyl alcohol, 1% sodium cholate, 0.5% Pluronic F127 (F127) and 2% Tween-80 were initially tested. Of the four surfactants tested, PLGA NPs in 0.5% F127 and 2% Tween-80 had the highest cell binding. These two surfactants were then retested in two different concentrations, 0.5% and 2%. The Fab-decorated PLGA NPs in 2% F127 had the highest cell binding. This study highlights the impact of common surfactants and their concentrations on the downstream targeting of ligand-decorated NPs. Similar principles should be applied in the development of future targeted nanosystems where surfactants are employed. Copyright © 2018 Elsevier B.V. All rights reserved.

  16. The role of conformational selection in the molecular recognition of the wild type and mutants XPA67-80 peptides by ERCC1.

    PubMed

    Fadda, Elisa

    2015-07-01

    Molecular recognition is a fundamental step in the coordination of biomolecular pathways. Understanding how recognition and binding occur between highly flexible protein domains is a complex task. The conformational selection theory provides an elegant rationalization of the recognition mechanism, especially valid in cases when unstructured protein regions are involved. The recognition of a poorly structured peptide, namely XPA67-80 , by its target receptor ERCC1, falls in this challenging study category. The microsecond molecular dynamics (MD) simulations, discussed in this work, show that the conformational propensity of the wild type XPA67-80 peptide in solution supports conformational selection as the key mechanism driving its molecular recognition by ERCC1. Moreover, all the mutations of the XPA67-80 peptide studied here cause a significant increase of its conformational disorder, relative to the wild type. Comparison to experimental data suggests that the loss of the recognized structural motifs at the microscopic time scale can contribute to the critical decrease in binding observed for one of the mutants, further substantiating the key role of conformational selection in recognition. Ultimately, because of the high sequence identity and analogy in binding, it is conceivable that the conclusions of this study on the XPA67-80 peptide also apply to the ERCC1-binding domain of the XPA protein. © 2015 Wiley Periodicals, Inc.

  17. Vigilante: Ultrafast Smart Sensor for Target Recognition and Precision Tracking in a Simulated CMD Scenario

    NASA Technical Reports Server (NTRS)

    Uldomkesmalee, Suraphol; Suddarth, Steven C.

    1997-01-01

    VIGILANTE is an ultrafast smart sensor testbed for generic Automatic Target Recognition (ATR) applications with a series of capability demonstration focussed on cruise missile defense (CMD). VIGILANTE's sensor/processor architecture is based on next-generation UV/visible/IR sensors and a tera-operations per second sugar-cube processor, as well as supporting airborne vehicle. Excellent results of efficient ATR methodologies that use an eigenvectors/neural network combination and feature-based precision tracking have been demonstrated in the laboratory environment.

  18. Structures of BIR domains from human NAIP and cIAP2.

    PubMed

    Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

    2009-11-01

    The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1'-P4' side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3' position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2' and P4' pockets make similar interactions to those seen in other BIR domain-peptide complexes. The structures also reveal how a serine in the P1' position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins.

  19. Chemiresistive and Gravimetric Dual-Mode Gas Sensor toward Target Recognition and Differentiation.

    PubMed

    Chen, Yan; Zhang, Hao; Feng, Zhihong; Zhang, Hongxiang; Zhang, Rui; Yu, Yuanyuan; Tao, Jin; Zhao, Hongyuan; Guo, Wenlan; Pang, Wei; Duan, Xuexin; Liu, Jing; Zhang, Daihua

    2016-08-24

    We demonstrate a dual-mode gas sensor for simultaneous and independent acquisition of electrical and mechanical signals from the same gas adsorption event. The device integrates a graphene field-effect transistor (FET) with a piezoelectric resonator in a seamless manner by leveraging multiple structural and functional synergies. Dual signals resulting from independent physical processes, i.e., mass attachment and charge transfer can reflect intrinsic properties of gas molecules and potentially enable target recognition and quantification at the same time. Fabrication of the device is based on standard Integrated Circuit (IC) foundry processes and fully compatible with system-on-a-chip (SoC) integration to achieve extremely small form factors. In addition, the ability of simultaneous measurements of mass adsorption and charge transfer guides us to a more precise understanding of the interactions between graphene and various gas molecules. Besides its practical functions, the device serves as an effective tool to quantitatively investigate the physical processes and sensing mechanisms for a large library of sensing materials and target analytes.

  20. Identification of influenza A nucleoprotein body domain residues essential for viral RNA expression expose antiviral target.

    PubMed

    Davis, Alicia M; Ramirez, Jose; Newcomb, Laura L

    2017-02-07

    Influenza A virus is controlled with yearly vaccination while emerging global pandemics are kept at bay with antiviral medications. Unfortunately, influenza A viruses have emerged resistance to approved influenza antivirals. Accordingly, there is an urgent need for novel antivirals to combat emerging influenza A viruses resistant to current treatments. Conserved viral proteins are ideal targets because conserved protein domains are present in most, if not all, influenza subtypes, and are presumed less prone to evolve viable resistant versions. The threat of an antiviral resistant influenza pandemic justifies our study to identify and characterize antiviral targets within influenza proteins that are highly conserved. Influenza A nucleoprotein (NP) is highly conserved and plays essential roles throughout the viral lifecycle, including viral RNA synthesis. Using NP crystal structure, we targeted accessible amino acids for substitution. To characterize the NP proteins, reconstituted viral ribonucleoproteins (vRNPs) were expressed in 293 T cells, RNA was isolated, and reverse transcription - quantitative PCR (RT-qPCR) was employed to assess viral RNA expressed from reconstituted vRNPs. Location was confirmed using cellular fractionation and western blot, along with observation of NP-GFP fusion proteins. Nucleic acid binding, oligomerization, and vRNP formation, were each assessed with native gel electrophoresis. Here we report characterization of an accessible and conserved five amino acid region within the NP body domain that plays a redundant but essential role in viral RNA synthesis. Our data demonstrate substitutions in this domain did not alter NP localization, oligomerization, or ability to bind nucleic acids, yet resulted in a defect in viral RNA expression. To define this region further, single and double amino acid substitutions were constructed and investigated. All NP single substitutions were functional, suggesting redundancy, yet different combinations of

  1. Carbohydrate recognition by the antiviral lectin cyanovirin-N

    PubMed Central

    Fujimoto, Yukiji K.; Green, David F.

    2012-01-01

    Cyanovirin-N is a cyanobacterial lectin with potent antiviral activity, and has been the focus of extensive pre-clinical investigation as a potential prophylactic for the prevention of the sexual transmission of the human immunodeficiency virus (HIV). Here we present a detailed analysis of carbohydrate recognition by this important protein, using a combination of computational methods, including extensive molecular dynamics simulations and Molecular-Mechanics/ Poisson–Boltzmann/Surface-Area (MM/PBSA) energetic analysis. The simulation results strongly suggest that the observed tendency of wildtype CVN to form domain-swapped dimers is the result of a previously unidentified cis-peptide bond present in the monomeric state. The energetic analysis additionally indicates that the highest-affinity ligand for CVN characterized to date (α-Man-(1,2)-α-Man-(1,2)-α-Man) is recognized asymmetrically by the two binding sites. Finally, we are able to provide a detailed map of the role of all binding site functional groups (both backbone and side chain) to various aspects of molecular recognition: general affinity for cognate ligands, specificity for distinct oligosaccharide targets and the asymmetric recognition of α-Man-(1,2)-α-Man-(1,2)-α-Man. Taken as a whole, these results complement past experimental characterization (both structural and thermodynamic) to provide the most complete understanding of carbohydrate recognition by CVN to date. The results also provide strong support for the application of similar approaches to the understanding of other protein–carbohydrate complexes. PMID:23057413

  2. Familiar Person Recognition: Is Autonoetic Consciousness More Likely to Accompany Face Recognition Than Voice Recognition?

    NASA Astrophysics Data System (ADS)

    Barsics, Catherine; Brédart, Serge

    2010-11-01

    Autonoetic consciousness is a fundamental property of human memory, enabling us to experience mental time travel, to recollect past events with a feeling of self-involvement, and to project ourselves in the future. Autonoetic consciousness is a characteristic of episodic memory. By contrast, awareness of the past associated with a mere feeling of familiarity or knowing relies on noetic consciousness, depending on semantic memory integrity. Present research was aimed at evaluating whether conscious recollection of episodic memories is more likely to occur following the recognition of a familiar face than following the recognition of a familiar voice. Recall of semantic information (biographical information) was also assessed. Previous studies that investigated the recall of biographical information following person recognition used faces and voices of famous people as stimuli. In this study, the participants were presented with personally familiar people's voices and faces, thus avoiding the presence of identity cues in the spoken extracts and allowing a stricter control of frequency exposure with both types of stimuli (voices and faces). In the present study, the rate of retrieved episodic memories, associated with autonoetic awareness, was significantly higher from familiar faces than familiar voices even though the level of overall recognition was similar for both these stimuli domains. The same pattern was observed regarding semantic information retrieval. These results and their implications for current Interactive Activation and Competition person recognition models are discussed.

  3. The auto-inhibitory state of Rho guanine nucleotide exchange factor ARHGEF5/TIM can be relieved by targeting its SH3 domain with rationally designed peptide aptamers.

    PubMed

    He, Ping; Tan, De-Li; Liu, Hong-Xiang; Lv, Feng-Lin; Wu, Wei

    2015-04-01

    The short isoform of Rho guanine nucleotide exchange factor ARHGEF5 is known as TIM, which plays diverse roles in, for example, tumorigenesis, neuronal development and Src-induced podosome formation through the activation of its substrates, the Rho family of GTPases. The activation is auto-inhibited by a putative helix N-terminal to the DH domain of TIM, which is stabilized by the intramolecular interaction of C-terminal SH3 domain with a poly-proline sequence between the putative helix and the DH domain. In this study, we systematically investigated the structural basis, energetic landscape and biological implication underlying TIM auto-inhibition by using atomistic molecular dynamics simulations and binding free energy analysis. The computational study revealed that the binding of SH3 domain to poly-proline sequence is the prerequisite for the stabilization of TIM auto-inhibition. Thus, it is suggested that targeting SH3 domain with competitors of the poly-proline sequence would be a promising strategy to relieve the auto-inhibitory state of TIM. In this consideration, we rationally designed a number of peptide aptamers for competitively inhibiting the SH3 domain based on modeled TIM structure and computationally generated data. Peptide binding test and guanine nucleotide exchange analysis solidified that these designed peptides can both bind to the SH3 domain potently and activate TIM-catalyzed RhoA exchange reaction effectively. Interestingly, a positive correlation between the peptide affinity and induced exchange activity was observed. In addition, separate mutation of three conserved residues Pro49, Pro52 and Lys54 - they are required for peptide recognition by SH3 domain -- in a designed peptide to Ala would completely abolish the capability of this peptide activating TIM. All these come together to suggest an intrinsic relationship between peptide binding to SH3 domain and the activation of TIM. Copyright © 2015 Elsevier B.V. and Société Française de

  4. FPGA design of correlation-based pattern recognition

    NASA Astrophysics Data System (ADS)

    Jridi, Maher; Alfalou, Ayman

    2017-05-01

    Optical/Digital pattern recognition and tracking based on optical/digital correlation are a well-known techniques to detect, identify and localize a target object in a scene. Despite the limited number of treatments required by the correlation scheme, computational time and resources are relatively high. The most computational intensive treatment required by the correlation is the transformation from spatial to spectral domain and then from spectral to spatial domain. Furthermore, these transformations are used on optical/digital encryption schemes like the double random phase encryption (DRPE). In this paper, we present a VLSI architecture for the correlation scheme based on the fast Fourier transform (FFT). One interesting feature of the proposed scheme is its ability to stream image processing in order to perform correlation for video sequences. A trade-off between the hardware consumption and the robustness of the correlation can be made in order to understand the limitations of the correlation implementation in reconfigurable and portable platforms. Experimental results obtained from HDL simulations and FPGA prototype have demonstrated the advantages of the proposed scheme.

  5. New approach for logo recognition

    NASA Astrophysics Data System (ADS)

    Chen, Jingying; Leung, Maylor K. H.; Gao, Yongsheng

    2000-03-01

    The problem of logo recognition is of great interest in the document domain, especially for document database. By recognizing the logo we obtain semantic information about the document which may be useful in deciding whether or not to analyze the textual components. In order to develop a logo recognition method that is efficient to compute and product intuitively reasonable results, we investigate the Line Segment Hausdorff Distance on logo recognition. Researchers apply Hausdorff Distance to measure the dissimilarity of two point sets. It has been extended to match two sets of line segments. The new approach has the advantage to incorporate structural and spatial information to compute the dissimilarity. The added information can conceptually provide more and better distinctive capability for recognition. The proposed technique has been applied on line segments of logos with encouraging results that support the concept experimentally. This might imply a new way for logo recognition.

  6. The crystal structure of the Sox4 HMG domain-DNA complex suggests a mechanism for positional interdependence in DNA recognition.

    PubMed

    Jauch, Ralf; Ng, Calista K L; Narasimhan, Kamesh; Kolatkar, Prasanna R

    2012-04-01

    It has recently been proposed that the sequence preferences of DNA-binding TFs (transcription factors) can be well described by models that include the positional interdependence of the nucleotides of the target sites. Such binding models allow for multiple motifs to be invoked, such as principal and secondary motifs differing at two or more nucleotide positions. However, the structural mechanisms underlying the accommodation of such variant motifs by TFs remain elusive. In the present study we examine the crystal structure of the HMG (high-mobility group) domain of Sox4 [Sry (sex-determining region on the Y chromosome)-related HMG box 4] bound to DNA. By comparing this structure with previously solved structures of Sox17 and Sox2, we observed subtle conformational differences at the DNA-binding interface. Furthermore, using quantitative electrophoretic mobility-shift assays we validated the positional interdependence of two nucleotides and the presence of a secondary Sox motif in the affinity landscape of Sox4. These results suggest that a concerted rearrangement of two interface amino acids enables Sox4 to accommodate primary and secondary motifs. The structural adaptations lead to altered dinucleotide preferences that mutually reinforce each other. These analyses underline the complexity of the DNA recognition by TFs and provide an experimental validation for the conceptual framework of positional interdependence and secondary binding motifs.

  7. Structural characterization of human galectin-4 C-terminal domain: elucidating the molecular basis for recognition of glycosphingolipids, sulfated saccharides and blood group antigens.

    PubMed

    Bum-Erdene, Khuchtumur; Leffler, Hakon; Nilsson, Ulf J; Blanchard, Helen

    2015-09-01

    Human galectin-4 is a lectin that is expressed mainly in the gastrointestinal tract and exhibits metastasis-promoting roles in some cancers. Its tandem-repeat nature exhibits two distinct carbohydrate recognition domains allowing crosslinking by simultaneous binding to sulfated and non-sulfated (but not sialylated) glycosphingolipids and glycoproteins, facilitating stabilization of lipid rafts. Critically, galectin-4 exerts favourable or unfavourable effects depending upon the cancer. Here we report the first X-ray crystallographic structural information on human galectin-4, specifically the C-terminal carbohydrate recognition domain of human (galectin-4C) in complex with lactose, lactose-3'-sulfate, 2'-fucosyllactose, lacto-N-tetraose and lacto-N-neotetraose. These structures enable elucidation of galectin-4C binding fine-specificity towards sulfated and non-sulfated lacto- and neolacto-series sphingolipids as well as to human blood group antigens. Analysis of the lactose-3'-sulfate complex structure shows that galectin-4C does not recognize the sulfate group using any specific amino acid, but binds the ligand nonetheless. Complex structures with lacto-N-tetraose and lacto-N-neotetraose displayed differences in binding interactions exhibited by the non-reducing-end galactose. That of lacto-N-tetraose points outward from the protein surface whereas that of lacto-N-neotetraose interacts directly with the protein. Recognition patterns of human galectin-4C towards lacto- and neolacto-series glycosphingolipids are similar to those of human galectin-3; however, detailed scrutiny revealed differences stemming from the extended binding site that offer distinction in ligand profiles of these two galectins. Structural characterization of the complex with 2'-fucosyllactose, a carbohydrate with similarity to the H antigen, and molecular dynamics studies highlight structural features that allow specific recognition of A and B antigens, whilst a lack of interaction with the 2

  8. Differential recognition of terminal extracellular Plasmodium falciparum VAR2CSA domains by sera from multigravid, malaria-exposed Malian women.

    PubMed

    Travassos, Mark A; Coulibaly, Drissa; Bailey, Jason A; Niangaly, Amadou; Adams, Matthew; Nyunt, Myaing M; Ouattara, Amed; Lyke, Kirsten E; Laurens, Matthew B; Pablo, Jozelyn; Jasinskas, Algis; Nakajima, Rie; Berry, Andrea A; Takala-Harrison, Shannon; Kone, Abdoulaye K; Kouriba, Bourema; Rowe, J Alexandra; Doumbo, Ogobara K; Thera, Mahamadou A; Laufer, Miriam K; Felgner, Philip L; Plowe, Christopher V

    2015-06-01

    The Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) family mediates parasite sequestration in small capillaries through tissue-specific cytoadherence. The best characterized of these proteins is VAR2CSA, which is expressed on the surface of infected erythrocytes that bind to chondroitin sulfate in the placental matrix. Antibodies to VAR2CSA prevent placental cytoadherence and protect against placental malaria. The size and complexity of the VAR2CSA protein pose challenges for vaccine development, but smaller constitutive domains may be suitable for subunit vaccine development. A protein microarray was printed to include five overlapping fragments of the 3D7 VAR2CSA extracellular region. Malian women with a history of at least one pregnancy had antibody recognition of four of these fragments and had stronger reactivity against the two distal fragments than did nulliparous women, children, and men from Mali, suggesting that the C-terminal extracellular VAR2CSA domains are a potential focus of protective immunity. With carefully chosen sera from longitudinal studies of pregnant women, this approach has the potential to identify seroreactive VAR2CSA domains associated with protective immunity against pregnancy-associated malaria. © The American Society of Tropical Medicine and Hygiene.

  9. Multi-source feature extraction and target recognition in wireless sensor networks based on adaptive distributed wavelet compression algorithms

    NASA Astrophysics Data System (ADS)

    Hortos, William S.

    2008-04-01

    Proposed distributed wavelet-based algorithms are a means to compress sensor data received at the nodes forming a wireless sensor network (WSN) by exchanging information between neighboring sensor nodes. Local collaboration among nodes compacts the measurements, yielding a reduced fused set with equivalent information at far fewer nodes. Nodes may be equipped with multiple sensor types, each capable of sensing distinct phenomena: thermal, humidity, chemical, voltage, or image signals with low or no frequency content as well as audio, seismic or video signals within defined frequency ranges. Compression of the multi-source data through wavelet-based methods, distributed at active nodes, reduces downstream processing and storage requirements along the paths to sink nodes; it also enables noise suppression and more energy-efficient query routing within the WSN. Targets are first detected by the multiple sensors; then wavelet compression and data fusion are applied to the target returns, followed by feature extraction from the reduced data; feature data are input to target recognition/classification routines; targets are tracked during their sojourns through the area monitored by the WSN. Algorithms to perform these tasks are implemented in a distributed manner, based on a partition of the WSN into clusters of nodes. In this work, a scheme of collaborative processing is applied for hierarchical data aggregation and decorrelation, based on the sensor data itself and any redundant information, enabled by a distributed, in-cluster wavelet transform with lifting that allows multiple levels of resolution. The wavelet-based compression algorithm significantly decreases RF bandwidth and other resource use in target processing tasks. Following wavelet compression, features are extracted. The objective of feature extraction is to maximize the probabilities of correct target classification based on multi-source sensor measurements, while minimizing the resource expenditures at

  10. A Compact Methodology to Understand, Evaluate, and Predict the Performance of Automatic Target Recognition

    PubMed Central

    Li, Yanpeng; Li, Xiang; Wang, Hongqiang; Chen, Yiping; Zhuang, Zhaowen; Cheng, Yongqiang; Deng, Bin; Wang, Liandong; Zeng, Yonghu; Gao, Lei

    2014-01-01

    This paper offers a compacted mechanism to carry out the performance evaluation work for an automatic target recognition (ATR) system: (a) a standard description of the ATR system's output is suggested, a quantity to indicate the operating condition is presented based on the principle of feature extraction in pattern recognition, and a series of indexes to assess the output in different aspects are developed with the application of statistics; (b) performance of the ATR system is interpreted by a quality factor based on knowledge of engineering mathematics; (c) through a novel utility called “context-probability” estimation proposed based on probability, performance prediction for an ATR system is realized. The simulation result shows that the performance of an ATR system can be accounted for and forecasted by the above-mentioned measures. Compared to existing technologies, the novel method can offer more objective performance conclusions for an ATR system. These conclusions may be helpful in knowing the practical capability of the tested ATR system. At the same time, the generalization performance of the proposed method is good. PMID:24967605

  11. Receptor-binding domain as a target for developing SARS vaccines.

    PubMed

    Zhu, Xiaojie; Liu, Qi; Du, Lanying; Lu, Lu; Jiang, Shibo

    2013-08-01

    A decade ago, severe acute respiratory syndrome (SARS) coronavirus (SARS-CoV) caused a global pandemic with a mortality rate of 10%. Reports of recent outbreaks of a SARS-like disease caused by Middle East respiratory syndrome coronavirus (MERS-CoV) have raised serious concerns of a possible reemergence of SARS-CoV, either by laboratory escape or the presence of a natural reservoir. Therefore, the development of effective and safe SARS vaccines is still needed. Based on our previous studies, we believe that the receptor-binding domain (RBD) in the S1 subunit of the SARS-CoV spike (S) protein is the most important target for developing a SARS vaccine. In particular, RBD of S protein contains the critical neutralizing domain (CND), which is able to induce highly potent neutralizing antibody response and cross-protection against divergent SARS-CoV strains. Furthermore, a RBD-based subunit vaccine is expected to be safer than other vaccines that may induce Th2-type immunopathology. This review will discuss key advances in the development of RBD-based SARS vaccines and the possibility of using a similar strategy to develop vaccines against MERS-CoV.

  12. Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach.

    PubMed

    Amato, Anastasia; Lucas, Xavier; Bortoluzzi, Alessio; Wright, David; Ciulli, Alessio

    2018-04-20

    Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers.

  13. Chemical recognition of gases and gas mixtures with terahertz waves.

    PubMed

    Jacobsen, R H; Mittleman, D M; Nuss, M C

    1996-12-15

    A time-domain chemical-recognition system for classifying gases and analyzing gas mixtures is presented. We analyze the free induction decay exhibited by gases excited by far-infrared (terahertz) pulses in the time domain, using digital signal-processing techniques. A simple geometric picture is used for the classif ication of the waveforms measured for unknown gas species. We demonstrate how the recognition system can be used to determine the partial pressures of an ammonia-water gas mixture.

  14. Chemical recognition of gases and gas mixtures with terahertz waves

    NASA Astrophysics Data System (ADS)

    Jacobsen, R. H.; Mittleman, D. M.; Nuss, M. C.

    1996-12-01

    A time-domain chemical-recognition system for classifying gases and analyzing gas mixtures is presented. We analyze the free induction decay exhibited by gases excited by far-infrared (terahertz) pulses in the time domain, using digital signal-processing techniques. A simple geometric picture is used for the classification of the waveforms measured for unknown gas species. We demonstrate how the recognition system can be used to determine the partial pressures of an ammonia-water gas mixture.

  15. Radar HRRP Target Recognition Based on Stacked Autoencoder and Extreme Learning Machine

    PubMed Central

    Liu, Yongxiang; Huo, Kai; Zhang, Zhongshuai

    2018-01-01

    A novel radar high-resolution range profile (HRRP) target recognition method based on a stacked autoencoder (SAE) and extreme learning machine (ELM) is presented in this paper. As a key component of deep structure, the SAE does not only learn features by making use of data, it also obtains feature expressions at different levels of data. However, with the deep structure, it is hard to achieve good generalization performance with a fast learning speed. ELM, as a new learning algorithm for single hidden layer feedforward neural networks (SLFNs), has attracted great interest from various fields for its fast learning speed and good generalization performance. However, ELM needs more hidden nodes than conventional tuning-based learning algorithms due to the random set of input weights and hidden biases. In addition, the existing ELM methods cannot utilize the class information of targets well. To solve this problem, a regularized ELM method based on the class information of the target is proposed. In this paper, SAE and the regularized ELM are combined to make full use of their advantages and make up for each of their shortcomings. The effectiveness of the proposed method is demonstrated by experiments with measured radar HRRP data. The experimental results show that the proposed method can achieve good performance in the two aspects of real-time and accuracy, especially when only a few training samples are available. PMID:29320453

  16. Radar HRRP Target Recognition Based on Stacked Autoencoder and Extreme Learning Machine.

    PubMed

    Zhao, Feixiang; Liu, Yongxiang; Huo, Kai; Zhang, Shuanghui; Zhang, Zhongshuai

    2018-01-10

    A novel radar high-resolution range profile (HRRP) target recognition method based on a stacked autoencoder (SAE) and extreme learning machine (ELM) is presented in this paper. As a key component of deep structure, the SAE does not only learn features by making use of data, it also obtains feature expressions at different levels of data. However, with the deep structure, it is hard to achieve good generalization performance with a fast learning speed. ELM, as a new learning algorithm for single hidden layer feedforward neural networks (SLFNs), has attracted great interest from various fields for its fast learning speed and good generalization performance. However, ELM needs more hidden nodes than conventional tuning-based learning algorithms due to the random set of input weights and hidden biases. In addition, the existing ELM methods cannot utilize the class information of targets well. To solve this problem, a regularized ELM method based on the class information of the target is proposed. In this paper, SAE and the regularized ELM are combined to make full use of their advantages and make up for each of their shortcomings. The effectiveness of the proposed method is demonstrated by experiments with measured radar HRRP data. The experimental results show that the proposed method can achieve good performance in the two aspects of real-time and accuracy, especially when only a few training samples are available.

  17. Mixed Pattern Matching-Based Traffic Abnormal Behavior Recognition

    PubMed Central

    Cui, Zhiming; Zhao, Pengpeng

    2014-01-01

    A motion trajectory is an intuitive representation form in time-space domain for a micromotion behavior of moving target. Trajectory analysis is an important approach to recognize abnormal behaviors of moving targets. Against the complexity of vehicle trajectories, this paper first proposed a trajectory pattern learning method based on dynamic time warping (DTW) and spectral clustering. It introduced the DTW distance to measure the distances between vehicle trajectories and determined the number of clusters automatically by a spectral clustering algorithm based on the distance matrix. Then, it clusters sample data points into different clusters. After the spatial patterns and direction patterns learned from the clusters, a recognition method for detecting vehicle abnormal behaviors based on mixed pattern matching was proposed. The experimental results show that the proposed technical scheme can recognize main types of traffic abnormal behaviors effectively and has good robustness. The real-world application verified its feasibility and the validity. PMID:24605045

  18. Structural insight into RNA recognition motifs: versatile molecular Lego building blocks for biological systems.

    PubMed

    Muto, Yutaka; Yokoyama, Shigeyuki

    2012-01-01

    'RNA recognition motifs (RRMs)' are common domain-folds composed of 80-90 amino-acid residues in eukaryotes, and have been identified in many cellular proteins. At first they were known as RNA binding domains. Through discoveries over the past 20 years, however, the RRMs have been shown to exhibit versatile molecular recognition activities and to behave as molecular Lego building blocks to construct biological systems. Novel RNA/protein recognition modes by RRMs are being identified, and more information about the molecular recognition by RRMs is becoming available. These RNA/protein recognition modes are strongly correlated with their biological significance. In this review, we would like to survey the recent progress on these versatile molecular recognition modules. Copyright © 2012 John Wiley & Sons, Ltd.

  19. SH2 Domains Recognize Contextual Peptide Sequence Information to Determine Selectivity*

    PubMed Central

    Liu, Bernard A.; Jablonowski, Karl; Shah, Eshana E.; Engelmann, Brett W.; Jones, Richard B.; Nash, Piers D.

    2010-01-01

    Selective ligand recognition by modular protein interaction domains is a primary determinant of specificity in signaling pathways. Src homology 2 (SH2) domains fulfill this capacity immediately downstream of tyrosine kinases, acting to recruit their host polypeptides to ligand proteins harboring phosphorylated tyrosine residues. The degree to which SH2 domains are selective and the mechanisms underlying selectivity are fundamental to understanding phosphotyrosine signaling networks. An examination of interactions between 50 SH2 domains and a set of 192 phosphotyrosine peptides corresponding to physiological motifs within FGF, insulin, and IGF-1 receptor pathways indicates that individual SH2 domains have distinct recognition properties and exhibit a remarkable degree of selectivity beyond that predicted by previously described binding motifs. The underlying basis for such selectivity is the ability of SH2 domains to recognize both permissive amino acid residues that enhance binding and non-permissive amino acid residues that oppose binding in the vicinity of the essential phosphotyrosine. Neighboring positions affect one another so local sequence context matters to SH2 domains. This complex linguistics allows SH2 domains to distinguish subtle differences in peptide ligands. This newly appreciated contextual dependence substantially increases the accessible information content embedded in the peptide ligands that can be effectively integrated to determine binding. This concept may serve more broadly as a paradigm for subtle recognition of physiological ligands by protein interaction domains. PMID:20627867

  20. Development and Evaluation of Single Domain Antibodies for Vaccinia and the L1 Antigen

    PubMed Central

    Walper, Scott A.; Liu, Jinny L.; Zabetakis, Daniel; Anderson, George P.; Goldman, Ellen R.

    2014-01-01

    There is ongoing interest to develop high affinity, thermal stable recognition elements to replace conventional antibodies in biothreat detection assays. As part of this effort, single domain antibodies that target vaccinia virus were developed. Two llamas were immunized with killed viral particles followed by boosts with the recombinant membrane protein, L1, to stimulate the immune response for envelope and membrane proteins of the virus. The variable domains of the induced heavy chain antibodies were selected from M13 phage display libraries developed from isolated RNA. Selection via biopanning on the L1 antigen produced single domain antibodies that were specific and had affinities ranging from 4×10−9 M to 7.0×10−10 M, as determined by surface plasmon resonance. Several showed good ability to refold after heat denaturation. These L1-binding single domain antibodies, however, failed to recognize the killed vaccinia antigen. Useful vaccinia binding single domain antibodies were isolated by a second selection using the killed virus as the target. The virus binding single domain antibodies were incorporated in sandwich assays as both capture and tracer using the MAGPIX system yielding limits of detection down to 4×105 pfu/ml, a four-fold improvement over the limit obtained using conventional antibodies. This work demonstrates the development of anti-vaccinia single domain antibodies and their incorporation into sandwich assays for viral detection. It also highlights the properties of high affinity and thermal stability that are hallmarks of single domain antibodies. PMID:25211488

  1. Sequence Discrimination by Alternatively Spliced Isoforms of a DNA Binding Zinc Finger Domain

    NASA Astrophysics Data System (ADS)

    Gogos, Joseph A.; Hsu, Tien; Bolton, Jesse; Kafatos, Fotis C.

    1992-09-01

    Two major developmentally regulated isoforms of the Drosophila chorion transcription factor CF2 differ by an extra zinc finger within the DNA binding domain. The preferred DNA binding sites were determined and are distinguished by an internal duplication of TAT in the site recognized by the isoform with the extra finger. The results are consistent with modular interactions between zinc fingers and trinucleotides and also suggest rules for recognition of AT-rich DNA sites by zinc finger proteins. The results show how modular finger interactions with trinucleotides can be used, in conjunction with alternative splicing, to alter the binding specificity and increase the spectrum of sites recognized by a DNA binding domain. Thus, CF2 may potentially regulate distinct sets of target genes during development.

  2. Age-Related Differences in Face Recognition: Neural Correlates of Repetition and Semantic Priming in Young and Older Adults

    ERIC Educational Resources Information Center

    Wiese, Holger; Komes, Jessica; Tüttenberg, Simone; Leidinger, Jana; Schweinberger, Stefan R.

    2017-01-01

    Difficulties in person recognition are among the common complaints associated with cognitive ageing. The present series of experiments therefore investigated face and person recognition in young and older adults. The authors examined how within-domain and cross-domain repetition as well as semantic priming affect familiar face recognition and…

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

    NASA Technical Reports Server (NTRS)

    Chao, Tien-Hsin; Stoner, William W.

    1993-01-01

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

  4. Emotion Recognition from EEG Signals Using Multidimensional Information in EMD Domain.

    PubMed

    Zhuang, Ning; Zeng, Ying; Tong, Li; Zhang, Chi; Zhang, Hanming; Yan, Bin

    2017-01-01

    This paper introduces a method for feature extraction and emotion recognition based on empirical mode decomposition (EMD). By using EMD, EEG signals are decomposed into Intrinsic Mode Functions (IMFs) automatically. Multidimensional information of IMF is utilized as features, the first difference of time series, the first difference of phase, and the normalized energy. The performance of the proposed method is verified on a publicly available emotional database. The results show that the three features are effective for emotion recognition. The role of each IMF is inquired and we find that high frequency component IMF1 has significant effect on different emotional states detection. The informative electrodes based on EMD strategy are analyzed. In addition, the classification accuracy of the proposed method is compared with several classical techniques, including fractal dimension (FD), sample entropy, differential entropy, and discrete wavelet transform (DWT). Experiment results on DEAP datasets demonstrate that our method can improve emotion recognition performance.

  5. A robust algorithm for automated target recognition using precomputed radar cross sections

    NASA Astrophysics Data System (ADS)

    Ehrman, Lisa M.; Lanterman, Aaron D.

    2004-09-01

    Passive radar is an emerging technology that offers a number of unique benefits, including covert operation. Many such systems are already capable of detecting and tracking aircraft. The goal of this work is to develop a robust algorithm for adding automated target recognition (ATR) capabilities to existing passive radar systems. In previous papers, we proposed conducting ATR by comparing the precomputed RCS of known targets to that of detected targets. To make the precomputed RCS as accurate as possible, a coordinated flight model is used to estimate aircraft orientation. Once the aircraft's position and orientation are known, it is possible to determine the incident and observed angles on the aircraft, relative to the transmitter and receiver. This makes it possible to extract the appropriate radar cross section (RCS) from our simulated database. This RCS is then scaled to account for propagation losses and the receiver's antenna gain. A Rician likelihood model compares these expected signals from different targets to the received target profile. We have previously employed Monte Carlo runs to gauge the probability of error in the ATR algorithm; however, generation of a statistically significant set of Monte Carlo runs is computationally intensive. As an alternative to Monte Carlo runs, we derive the relative entropy (also known as Kullback-Liebler distance) between two Rician distributions. Since the probability of Type II error in our hypothesis testing problem can be expressed as a function of the relative entropy via Stein's Lemma, this provides us with a computationally efficient method for determining an upper bound on our algorithm's performance. It also provides great insight into the types of classification errors we can expect from our algorithm. This paper compares the numerically approximated probability of Type II error with the results obtained from a set of Monte Carlo runs.

  6. Whole CMV Proteome Pattern Recognition Analysis after HSCT Identifies Unique Epitope Targets Associated with the CMV Status

    PubMed Central

    Pérez-Bercoff, Lena; Valentini, Davide; Gaseitsiwe, Simani; Mahdavifar, Shahnaz; Schutkowski, Mike; Poiret, Thomas; Pérez-Bercoff, Åsa; Ljungman, Per; Maeurer, Markus J.

    2014-01-01

    Cytomegalovirus (CMV) infection represents a vital complication after Hematopoietic Stem Cell Transplantation (HSCT). We screened the entire CMV proteome to visualize the humoral target epitope-focus profile in serum after HSCT. IgG profiling from four patient groups (donor and/or recipient +/− for CMV) was performed at 6, 12 and 24 months after HSCT using microarray slides containing 17174 of 15mer-peptides overlapping by 4 aa covering 214 proteins from CMV. Data were analyzed using maSigPro, PAM and the ‘exclusive recognition analysis (ERA)’ to identify unique CMV epitope responses for each patient group. The ‘exclusive recognition analysis’ of serum epitope patterns segregated best 12 months after HSCT for the D+/R+ group (versus D−/R−). Epitopes were derived from UL123 (IE1), UL99 (pp28), UL32 (pp150), this changed at 24 months to 2 strongly recognized peptides provided from UL123 and UL100. Strongly (IgG) recognized CMV targets elicited also robust cytokine production in T-cells from patients after HSCT defined by intracellular cytokine staining (IL-2, TNF, IFN and IL-17). High-content peptide microarrays allow epitope profiling of entire viral proteomes; this approach can be useful to map relevant targets for diagnostics and therapy in patients with well defined clinical endpoints. Peptide microarray analysis visualizes the breadth of B-cell immune reconstitution after HSCT and provides a useful tool to gauge immune reconstitution. PMID:24740411

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

    NASA Astrophysics Data System (ADS)

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

    2017-10-01

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

  8. The conserved RNA recognition motif and C3H1 domain of the Not4 ubiquitin ligase regulate in vivo ligase function.

    PubMed

    Chen, Hongfeng; Sirupangi, Tirupataiah; Wu, Zhao-Hui; Johnson, Daniel L; Laribee, R Nicholas

    2018-05-25

    The Ccr4-Not complex controls RNA polymerase II (Pol II) dependent gene expression and proteasome function. The Not4 ubiquitin ligase is a Ccr4-Not subunit that has both a RING domain and a conserved RNA recognition motif and C3H1 domain (referred to as the RRM-C domain) with unknown function. We demonstrate that while individual Not4 RING or RRM-C mutants fail to replicate the proteasomal defects found in Not4 deficient cells, mutation of both exhibits a Not4 loss of function phenotype. Transcriptome analysis revealed that the Not4 RRM-C affects a specific subset of Pol II-regulated genes, including those involved in transcription elongation, cyclin-dependent kinase regulated nutrient responses, and ribosomal biogenesis. The Not4 RING, RRM-C, or RING/RRM-C mutations cause a generalized increase in Pol II binding at a subset of these genes, yet their impact on gene expression does not always correlate with Pol II recruitment which suggests Not4 regulates their expression through additional mechanisms. Intriguingly, we find that while the Not4 RRM-C is dispensable for Ccr4-Not association with RNA Pol II, the Not4 RING domain is required for these interactions. Collectively, these data elucidate previously unknown roles for the conserved Not4 RRM-C and RING domains in regulating Ccr4-Not dependent functions in vivo.

  9. Targeting Ligandable Pockets on Plant Homeodomain (PHD) Zinc Finger Domains by a Fragment-Based Approach

    PubMed Central

    2018-01-01

    Plant homeodomain (PHD) zinc fingers are histone reader domains that are often associated with human diseases. Despite this, they constitute a poorly targeted class of readers, suggesting low ligandability. Here, we describe a successful fragment-based campaign targeting PHD fingers from the proteins BAZ2A and BAZ2B as model systems. We validated a pool of in silico fragments both biophysically and structurally and solved the first crystal structures of PHD zinc fingers in complex with fragments bound to an anchoring pocket at the histone binding site. The best-validated hits were found to displace a histone H3 tail peptide in competition assays. This work identifies new chemical scaffolds that provide suitable starting points for future ligand optimization using structure-guided approaches. The demonstrated ligandability of the PHD reader domains could pave the way for the development of chemical probes to drug this family of epigenetic readers. PMID:29529862

  10. Hierarchical Context Modeling for Video Event Recognition.

    PubMed

    Wang, Xiaoyang; Ji, Qiang

    2016-10-11

    Current video event recognition research remains largely target-centered. For real-world surveillance videos, targetcentered event recognition faces great challenges due to large intra-class target variation, limited image resolution, and poor detection and tracking results. To mitigate these challenges, we introduced a context-augmented video event recognition approach. Specifically, we explicitly capture different types of contexts from three levels including image level, semantic level, and prior level. At the image level, we introduce two types of contextual features including the appearance context features and interaction context features to capture the appearance of context objects and their interactions with the target objects. At the semantic level, we propose a deep model based on deep Boltzmann machine to learn event object representations and their interactions. At the prior level, we utilize two types of prior-level contexts including scene priming and dynamic cueing. Finally, we introduce a hierarchical context model that systematically integrates the contextual information at different levels. Through the hierarchical context model, contexts at different levels jointly contribute to the event recognition. We evaluate the hierarchical context model for event recognition on benchmark surveillance video datasets. Results show that incorporating contexts in each level can improve event recognition performance, and jointly integrating three levels of contexts through our hierarchical model achieves the best performance.

  11. Dual streams of auditory afferents target multiple domains in the primate prefrontal cortex

    PubMed Central

    Romanski, L. M.; Tian, B.; Fritz, J.; Mishkin, M.; Goldman-Rakic, P. S.; Rauschecker, J. P.

    2009-01-01

    ‘What’ and ‘where’ visual streams define ventrolateral object and dorsolateral spatial processing domains in the prefrontal cortex of nonhuman primates. We looked for similar streams for auditory–prefrontal connections in rhesus macaques by combining microelectrode recording with anatomical tract-tracing. Injection of multiple tracers into physiologically mapped regions AL, ML and CL of the auditory belt cortex revealed that anterior belt cortex was reciprocally connected with the frontal pole (area 10), rostral principal sulcus (area 46) and ventral prefrontal regions (areas 12 and 45), whereas the caudal belt was mainly connected with the caudal principal sulcus (area 46) and frontal eye fields (area 8a). Thus separate auditory streams originate in caudal and rostral auditory cortex and target spatial and non-spatial domains of the frontal lobe, respectively. PMID:10570492

  12. Phylogenetic analysis and expression profiling of the pattern recognition receptors: insights into molecular recognition of invading pathogens in Manduca sexta

    PubMed Central

    Zhang, Xiufeng; He, Yan; Cao, Xiaolong; Gunaratna, Ramesh T.; Chen, Yun-ru; Blissard, Gary; Kanost, Michael R.; Jiang, Haobo

    2015-01-01

    Pattern recognition receptors (PRRs) detect microbial pathogens and trigger innate immune responses. Previous biochemical studies have elucidated the physiological functions of eleven PRRs in Manduca sexta but our understanding of the recognition process is still limited, lacking genomic perspectives. While 34 C-type lectin-domain proteins and 16 Toll-like receptors are reported in the companion papers, we present here 120 other putative PRRs identified through the genome annotation. These include 76 leucine-rich repeat (LRR) proteins, 14 peptidoglycan recognition proteins, 6 EGF/Nim-domain proteins, 5 β-1,3-glucanase-related proteins, 4 galectins, 4 fibrinogen-related proteins, 3 thioester proteins, 5 immunoglobulin-domain proteins, 2 hemocytins, and 1 Reeler. Sequence alignment and phylogenetic analysis reveal the evolution history of a diverse repertoire of proteins for pathogen recognition. While functions of insect LRR proteins are mostly unknown, their structure diversification is phenomenal: In addition to the Toll homologs, 22 LRR proteins with a signal peptide are expected to be secreted; 18 LRR proteins lacking signal peptides may be cytoplasmic; 36 LRRs with a signal peptide and a transmembrane segment may be non-Toll receptors on the surface of cells. Expression profiles of the 120 genes in 52 tissue samples reflect complex regulation in various developmental stages and physiological states, including some likely by Rel family transcription factors via κB motifs in the promoter regions. This collection of information is expected to facilitate future biochemical studies detailing their respective roles in this model insect. PMID:25701384

  13. Conditional random fields for pattern recognition applied to structured data

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

    Burr, Tom; Skurikhin, Alexei

    In order to predict labels from an output domain, Y, pattern recognition is used to gather measurements from an input domain, X. Image analysis is one setting where one might want to infer whether a pixel patch contains an object that is “manmade” (such as a building) or “natural” (such as a tree). Suppose the label for a pixel patch is “manmade”; if the label for a nearby pixel patch is then more likely to be “manmade” there is structure in the output domain that can be exploited to improve pattern recognition performance. Modeling P(X) is difficult because features betweenmore » parts of the model are often correlated. Thus, conditional random fields (CRFs) model structured data using the conditional distribution P(Y|X = x), without specifying a model for P(X), and are well suited for applications with dependent features. Our paper has two parts. First, we overview CRFs and their application to pattern recognition in structured problems. Our primary examples are image analysis applications in which there is dependence among samples (pixel patches) in the output domain. Second, we identify research topics and present numerical examples.« less

  14. Conditional random fields for pattern recognition applied to structured data

    DOE PAGES

    Burr, Tom; Skurikhin, Alexei

    2015-07-14

    In order to predict labels from an output domain, Y, pattern recognition is used to gather measurements from an input domain, X. Image analysis is one setting where one might want to infer whether a pixel patch contains an object that is “manmade” (such as a building) or “natural” (such as a tree). Suppose the label for a pixel patch is “manmade”; if the label for a nearby pixel patch is then more likely to be “manmade” there is structure in the output domain that can be exploited to improve pattern recognition performance. Modeling P(X) is difficult because features betweenmore » parts of the model are often correlated. Thus, conditional random fields (CRFs) model structured data using the conditional distribution P(Y|X = x), without specifying a model for P(X), and are well suited for applications with dependent features. Our paper has two parts. First, we overview CRFs and their application to pattern recognition in structured problems. Our primary examples are image analysis applications in which there is dependence among samples (pixel patches) in the output domain. Second, we identify research topics and present numerical examples.« less

  15. Three-dimensional object recognition using similar triangles and decision trees

    NASA Technical Reports Server (NTRS)

    Spirkovska, Lilly

    1993-01-01

    A system, TRIDEC, that is capable of distinguishing between a set of objects despite changes in the objects' positions in the input field, their size, or their rotational orientation in 3D space is described. TRIDEC combines very simple yet effective features with the classification capabilities of inductive decision tree methods. The feature vector is a list of all similar triangles defined by connecting all combinations of three pixels in a coarse coded 127 x 127 pixel input field. The classification is accomplished by building a decision tree using the information provided from a limited number of translated, scaled, and rotated samples. Simulation results are presented which show that TRIDEC achieves 94 percent recognition accuracy in the 2D invariant object recognition domain and 98 percent recognition accuracy in the 3D invariant object recognition domain after training on only a small sample of transformed views of the objects.

  16. One-Reason Decision Making Unveiled: A Measurement Model of the Recognition Heuristic

    ERIC Educational Resources Information Center

    Hilbig, Benjamin E.; Erdfelder, Edgar; Pohl, Rudiger F.

    2010-01-01

    The fast-and-frugal recognition heuristic (RH) theory provides a precise process description of comparative judgments. It claims that, in suitable domains, judgments between pairs of objects are based on recognition alone, whereas further knowledge is ignored. However, due to the confound between recognition and further knowledge, previous…

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

    PubMed

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

    2012-01-09

    Behavioral and electrophysiological measures of target and distractor processing were examined in an auditory selective attention task before and after three weeks of distractor suppression training. Behaviorally, training improved target recognition and led to less conservative and more rapid responding. Training also effectively shortened the temporal distance between distractors and targets needed to achieve a fixed level of target sensitivity. The effects of training on event-related potentials were restricted to the distracting stimulus: earlier N1 latency, enhanced P2 amplitude, and weakened P3 amplitude. Nevertheless, as distractor P2 amplitude increased, so too did target P3 amplitude, connecting experience-dependent changes in distractor processing with greater distinctiveness of targets in working memory. We consider the effects of attention training on the processing priorities, representational noise, and inhibitory processes operating in working memory. Copyright © 2011 Elsevier B.V. All rights reserved.

  18. Intact suppression of increased false recognition in schizophrenia.

    PubMed

    Weiss, Anthony P; Dodson, Chad S; Goff, Donald C; Schacter, Daniel L; Heckers, Stephan

    2002-09-01

    Recognition memory is impaired in patients with schizophrenia, as they rely largely on item familiarity, rather than conscious recollection, to make mnemonic decisions. False recognition of novel items (foils) is increased in schizophrenia and may relate to this deficit in conscious recollection. By studying pictures of the target word during encoding, healthy adults can suppress false recognition. This study examined the effect of pictorial encoding on subsequent recognition of repeated foils in patients with schizophrenia. The study included 40 patients with schizophrenia and 32 healthy comparison subjects. After incidental encoding of 60 words or pictures, subjects were tested for recognition of target items intermixed with 60 new foils. These new foils were subsequently repeated following either a two- or 24-word delay. Subjects were instructed to label these repeated foils as new and not to mistake them for old target words. Schizophrenic patients showed greater overall false recognition of repeated foils. The rate of false recognition of repeated foils was lower after picture encoding than after word encoding. Despite higher levels of false recognition of repeated new items, patients and comparison subjects demonstrated a similar degree of false recognition suppression after picture, as compared to word, encoding. Patients with schizophrenia displayed greater false recognition of repeated foils than comparison subjects, suggesting both a decrement of item- (or source-) specific recollection and a consequent reliance on familiarity in schizophrenia. Despite these deficits, presenting pictorial information at encoding allowed schizophrenic subjects to suppress false recognition to a similar degree as the comparison group, implying the intact use of a high-level cognitive strategy in this population.

  19. AIDA: ab initio domain assembly for automated multi-domain protein structure prediction and domain–domain interaction prediction

    PubMed Central

    Xu, Dong; Jaroszewski, Lukasz; Li, Zhanwen; Godzik, Adam

    2015-01-01

    Motivation: Most proteins consist of multiple domains, independent structural and evolutionary units that are often reshuffled in genomic rearrangements to form new protein architectures. Template-based modeling methods can often detect homologous templates for individual domains, but templates that could be used to model the entire query protein are often not available. Results: We have developed a fast docking algorithm ab initio domain assembly (AIDA) for assembling multi-domain protein structures, guided by the ab initio folding potential. This approach can be extended to discontinuous domains (i.e. domains with ‘inserted’ domains). When tested on experimentally solved structures of multi-domain proteins, the relative domain positions were accurately found among top 5000 models in 86% of cases. AIDA server can use domain assignments provided by the user or predict them from the provided sequence. The latter approach is particularly useful for automated protein structure prediction servers. The blind test consisting of 95 CASP10 targets shows that domain boundaries could be successfully determined for 97% of targets. Availability and implementation: The AIDA package as well as the benchmark sets used here are available for download at http://ffas.burnham.org/AIDA/. Contact: adam@sanfordburnham.org Supplementary information: Supplementary data are available at Bioinformatics online. PMID:25701568

  20. Surface targeting of the dopamine transporter involves discrete epitopes in the distal C terminus but does not require canonical PDZ domain interactions.

    PubMed

    Bjerggaard, Christian; Fog, Jacob U; Hastrup, Hanne; Madsen, Kenneth; Loland, Claus J; Javitch, Jonathan A; Gether, Ulrik

    2004-08-04

    The human dopamine transporter (hDAT) contains a C-terminal type 2 PDZ (postsynaptic density 95/Discs large/zona occludens 1) domain-binding motif (LKV) known to interact with PDZ domain proteins such as PICK1 (protein interacting with C-kinase 1). As reported previously, we found that, after deletion of this motif, hDAT was retained in the endoplasmic reticulum (ER) of human embryonic kidney (HEK) 293 and Neuro2A cells, suggesting that PDZ domain interactions might be critical for hDAT targeting. Nonetheless, substitution of LKV with SLL, the type 1 PDZ-binding sequence from the beta2-adrenergic receptor, did not disrupt plasma membrane targeting. Moreover, the addition of an alanine to the hDAT C terminus (+Ala), resulting in an LKVA termination sequence, or substitution of LKV with alanines (3xAla_618-620) prevented neither plasma membrane targeting nor targeting into sprouting neurites of differentiated N2A cells. The inability of +Ala and 3xAla_618-620 to bind PDZ domains was confirmed by lack of colocalization with PICK1 in cotransfected HEK293 cells and by the inability of corresponding C-terminal fusion proteins to pull down purified PICK1. Thus, although residues in the hDAT C terminus are indispensable for proper targeting, PDZ domain interactions are not required. By progressive substitutions with beta2-adrenergic receptor sequence, and by triple-alanine substitutions in the hDAT C terminus, we examined the importance of epitopes preceding the LKV motif. Substitution of RHW(615-617) with alanines caused retention of the transporter in the ER despite preserved ability of this mutant to bind PICK1. We propose dual roles of the hDAT C terminus: a role independent of PDZ interactions for ER export and surface targeting, and a not fully clarified role involving PDZ interactions with proteins such as PICK1.

  1. Social appraisal influences recognition of emotions.

    PubMed

    Mumenthaler, Christian; Sander, David

    2012-06-01

    The notion of social appraisal emphasizes the importance of a social dimension in appraisal theories of emotion by proposing that the way an individual appraises an event is influenced by the way other individuals appraise and feel about the same event. This study directly tested this proposal by asking participants to recognize dynamic facial expressions of emotion (fear, happiness, or anger in Experiment 1; fear, happiness, anger, or neutral in Experiment 2) in a target face presented at the center of a screen while a contextual face, which appeared simultaneously in the periphery of the screen, expressed an emotion (fear, happiness, anger) or not (neutral) and either looked at the target face or not. We manipulated gaze direction to be able to distinguish between a mere contextual effect (gaze away from both the target face and the participant) and a specific social appraisal effect (gaze toward the target face). Results of both experiments provided evidence for a social appraisal effect in emotion recognition, which differed from the mere effect of contextual information: Whereas facial expressions were identical in both conditions, the direction of the gaze of the contextual face influenced emotion recognition. Social appraisal facilitated the recognition of anger, happiness, and fear when the contextual face expressed the same emotion. This facilitation was stronger than the mere contextual effect. Social appraisal also allowed better recognition of fear when the contextual face expressed anger and better recognition of anger when the contextual face expressed fear. 2012 APA, all rights reserved

  2. Modularly assembled designer TAL effector nucleases for targeted gene knockout and gene replacement in eukaryotes

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

    Li, T; Huang, S; Zhao, XF

    Recent studies indicate that the DNA recognition domain of transcription activator-like (TAL) effectors can be combined with the nuclease domain of FokI restriction enzyme to produce TAL effector nucleases (TALENs) that, in pairs, bind adjacent DNA target sites and produce double-strand breaks between the target sequences, stimulating non-homologous end-joining and homologous recombination. Here, we exploit the four prevalent TAL repeats and their DNA recognition cipher to develop a 'modular assembly' method for rapid production of designer TALENs (dTALENs) that recognize unique DNA sequence up to 23 bases in any gene. We have used this approach to engineer 10 dTALENs tomore » target specific loci in native yeast chromosomal genes. All dTALENs produced high rates of site-specific gene disruptions and created strains with expected mutant phenotypes. Moreover, dTALENs stimulated high rates (up to 34%) of gene replacement by homologous recombination. Finally, dTALENs caused no detectable cytotoxicity and minimal levels of undesired genetic mutations in the treated yeast strains. These studies expand the realm of verified TALEN activity from cultured human cells to an intact eukaryotic organism and suggest that low-cost, highly dependable dTALENs can assume a significant role for gene modifications of value in human and animal health, agriculture and industry.« less

  3. Recognition of the murine coronavirus genomic RNA packaging signal depends on the second RNA-binding domain of the nucleocapsid protein.

    PubMed

    Kuo, Lili; Koetzner, Cheri A; Hurst, Kelley R; Masters, Paul S

    2014-04-01

    The coronavirus nucleocapsid (N) protein forms a helical ribonucleoprotein with the viral positive-strand RNA genome and binds to the principal constituent of the virion envelope, the membrane (M) protein, to facilitate assembly and budding. Besides these structural roles, N protein associates with a component of the replicase-transcriptase complex, nonstructural protein 3, at a critical early stage of infection. N protein has also been proposed to participate in the replication and selective packaging of genomic RNA and the transcription and translation of subgenomic mRNA. Coronavirus N proteins contain two structurally distinct RNA-binding domains, an unusual characteristic among RNA viruses. To probe the functions of these domains in the N protein of the model coronavirus mouse hepatitis virus (MHV), we constructed mutants in which each RNA-binding domain was replaced by its counterpart from the N protein of severe acute respiratory syndrome coronavirus (SARS-CoV). Mapping of revertants of the resulting chimeric viruses provided evidence for extensive intramolecular interactions between the two RNA-binding domains. Through analysis of viral RNA that was packaged into virions we identified the second of the two RNA-binding domains as a principal determinant of MHV packaging signal recognition. As expected, the interaction of N protein with M protein was not affected in either of the chimeric viruses. Moreover, the SARS-CoV N substitutions did not alter the fidelity of leader-body junction formation during subgenomic mRNA synthesis. These results more clearly delineate the functions of N protein and establish a basis for further exploration of the mechanism of genomic RNA packaging. This work describes the interactions of the two RNA-binding domains of the nucleocapsid protein of a model coronavirus, mouse hepatitis virus. The main finding is that the second of the two domains plays an essential role in recognizing the RNA structure that allows the selective

  4. Structure of the Legionella Virulence Factor, SidC Reveals a Unique PI(4)P-Specific Binding Domain Essential for Its Targeting to the Bacterial Phagosome.

    PubMed

    Luo, Xi; Wasilko, David J; Liu, Yao; Sun, Jiayi; Wu, Xiaochun; Luo, Zhao-Qing; Mao, Yuxin

    2015-06-01

    The opportunistic intracellular pathogen Legionella pneumophila is the causative agent of Legionnaires' disease. L. pneumophila delivers nearly 300 effector proteins into host cells for the establishment of a replication-permissive compartment known as the Legionella-containing vacuole (LCV). SidC and its paralog SdcA are two effectors that have been shown to anchor on the LCV via binding to phosphatidylinositol-4-phosphate [PI(4)P] to facilitate the recruitment of ER proteins to the LCV. We recently reported that the N-terminal SNL (SidC N-terminal E3 Ligase) domain of SidC is a ubiquitin E3 ligase, and its activity is required for the recruitment of ER proteins to the LCV. Here we report the crystal structure of SidC (1-871). The structure reveals that SidC contains four domains that are packed into an arch-like shape. The P4C domain (PI(4)P binding of SidC) comprises a four α-helix bundle and covers the ubiquitin ligase catalytic site of the SNL domain. Strikingly, a pocket with characteristic positive electrostatic potentials is formed at one end of this bundle. Liposome binding assays of the P4C domain further identified the determinants of phosphoinositide recognition and membrane interaction. Interestingly, we also found that binding with PI(4)P stimulates the E3 ligase activity, presumably due to a conformational switch induced by PI(4)P from a closed form to an open active form. Mutations of key residues involved in PI(4)P binding significantly reduced the association of SidC with the LCV and abolished its activity in the recruitment of ER proteins and ubiquitin signals, highlighting that PI(4)P-mediated targeting of SidC is critical to its function in the remodeling of the bacterial phagosome membrane. Finally, a GFP-fusion with the P4C domain was demonstrated to be specifically localized to PI(4)P-enriched compartments in mammalian cells. This domain shows the potential to be developed into a sensitive and accurate PI(4)P probe in living cells.

  5. Material recognition based on thermal cues: Mechanisms and applications

    PubMed Central

    Ho, Hsin-Ni

    2018-01-01

    ABSTRACT Some materials feel colder to the touch than others, and we can use this difference in perceived coldness for material recognition. This review focuses on the mechanisms underlying material recognition based on thermal cues. It provides an overview of the physical, perceptual, and cognitive processes involved in material recognition. It also describes engineering domains in which material recognition based on thermal cues have been applied. This includes haptic interfaces that seek to reproduce the sensations associated with contact in virtual environments and tactile sensors aim for automatic material recognition. The review concludes by considering the contributions of this line of research in both science and engineering. PMID:29687043

  6. Material recognition based on thermal cues: Mechanisms and applications.

    PubMed

    Ho, Hsin-Ni

    2018-01-01

    Some materials feel colder to the touch than others, and we can use this difference in perceived coldness for material recognition. This review focuses on the mechanisms underlying material recognition based on thermal cues. It provides an overview of the physical, perceptual, and cognitive processes involved in material recognition. It also describes engineering domains in which material recognition based on thermal cues have been applied. This includes haptic interfaces that seek to reproduce the sensations associated with contact in virtual environments and tactile sensors aim for automatic material recognition. The review concludes by considering the contributions of this line of research in both science and engineering.

  7. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition.

    PubMed

    Tamayo, Joel V; Teramoto, Takamasa; Chatterjee, Seema; Hall, Traci M Tanaka; Gavis, Elizabeth R

    2017-04-04

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo's RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subset of Glo's functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  8. The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition

    DOE PAGES

    Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema; ...

    2017-04-04

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subsetmore » of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Lastly, our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.« less

  9. The Drosophila hnRNP F/H Homolog Glorund Uses Two Distinct RNA-Binding Modes to Diversify Target Recognition

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

    Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subsetmore » of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.« less

  10. The Drosophila hnRNP F/H homolog glorund uses two distinct RNA-binding modes to diversify target recognition

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

    Tamayo, Joel V.; Teramoto, Takamasa; Chatterjee, Seema

    The Drosophila hnRNP F/H homolog, Glorund (Glo), regulates nanos mRNA translation by interacting with a structured UA-rich motif in the nanos 3' untranslated region. Glo regulates additional RNAs, however, and mammalian homologs bind G-tract sequences to regulate alternative splicing, suggesting that Glo also recognizes G-tract RNA. To gain insight into how Glo recognizes both structured UA-rich and G-tract RNAs, we used mutational analysis guided by crystal structures of Glo’s RNA-binding domains and identified two discrete RNA-binding surfaces that allow Glo to recognize both RNA motifs. By engineering Glo variants that favor a single RNA-binding mode, we show that a subsetmore » of Glo’s functions in vivo is mediated solely by the G-tract binding mode, whereas regulation of nanos requires both recognition modes. Lastly, our findings suggest a molecular mechanism for the evolution of dual RNA motif recognition in Glo that may be applied to understanding the functional diversity of other RNA-binding proteins.« less

  11. Identification of the RNA recognition element of the RBPMS family of RNA-binding proteins and their transcriptome-wide mRNA targets

    PubMed Central

    Farazi, Thalia A.; Leonhardt, Carl S.; Mukherjee, Neelanjan; Mihailovic, Aleksandra; Li, Song; Max, Klaas E.A.; Meyer, Cindy; Yamaji, Masashi; Cekan, Pavol; Jacobs, Nicholas C.; Gerstberger, Stefanie; Bognanni, Claudia; Larsson, Erik; Ohler, Uwe; Tuschl, Thomas

    2014-01-01

    Recent studies implicated the RNA-binding protein with multiple splicing (RBPMS) family of proteins in oocyte, retinal ganglion cell, heart, and gastrointestinal smooth muscle development. These RNA-binding proteins contain a single RNA recognition motif (RRM), and their targets and molecular function have not yet been identified. We defined transcriptome-wide RNA targets using photoactivatable-ribonucleoside-enhanced crosslinking and immunoprecipitation (PAR-CLIP) in HEK293 cells, revealing exonic mature and intronic pre-mRNA binding sites, in agreement with the nuclear and cytoplasmic localization of the proteins. Computational and biochemical approaches defined the RNA recognition element (RRE) as a tandem CAC trinucleotide motif separated by a variable spacer region. Similar to other mRNA-binding proteins, RBPMS family of proteins relocalized to cytoplasmic stress granules under oxidative stress conditions suggestive of a support function for mRNA localization in large and/or multinucleated cells where it is preferentially expressed. PMID:24860013

  12. Oral streptococci utilize a Siglec-like domain of serine-rich repeat adhesins to preferentially target platelet sialoglycans in human blood.

    PubMed

    Deng, Lingquan; Bensing, Barbara A; Thamadilok, Supaporn; Yu, Hai; Lau, Kam; Chen, Xi; Ruhl, Stefan; Sullam, Paul M; Varki, Ajit

    2014-12-01

    Damaged cardiac valves attract blood-borne bacteria, and infective endocarditis is often caused by viridans group streptococci. While such bacteria use multiple adhesins to maintain their normal oral commensal state, recognition of platelet sialoglycans provides an intermediary for binding to damaged valvular endocardium. We use a customized sialoglycan microarray to explore the varied binding properties of phylogenetically related serine-rich repeat adhesins, the GspB, Hsa, and SrpA homologs from Streptococcus gordonii and Streptococcus sanguinis species, which belong to a highly conserved family of glycoproteins that contribute to virulence for a broad range of Gram-positive pathogens. Binding profiles of recombinant soluble homologs containing novel sialic acid-recognizing Siglec-like domains correlate well with binding of corresponding whole bacteria to arrays. These bacteria show multiple modes of glycan, protein, or divalent cation-dependent binding to synthetic glycoconjugates and isolated glycoproteins in vitro. However, endogenous asialoglycan-recognizing clearance receptors are known to ensure that only fully sialylated glycans dominate in the endovascular system, wherein we find these particular streptococci become primarily dependent on their Siglec-like adhesins for glycan-mediated recognition events. Remarkably, despite an excess of alternate sialoglycan ligands in cellular and soluble blood components, these adhesins selectively target intact bacteria to sialylated ligands on platelets, within human whole blood. These preferred interactions are inhibited by corresponding recombinant soluble adhesins, which also preferentially recognize platelets. Our data indicate that circulating platelets may act as inadvertent Trojan horse carriers of oral streptococci to the site of damaged endocardium, and provide an explanation why it is that among innumerable microbes that gain occasional access to the bloodstream, certain viridans group streptococci have a

  13. Kazakh Traditional Dance Gesture Recognition

    NASA Astrophysics Data System (ADS)

    Nussipbekov, A. K.; Amirgaliyev, E. N.; Hahn, Minsoo

    2014-04-01

    Full body gesture recognition is an important and interdisciplinary research field which is widely used in many application spheres including dance gesture recognition. The rapid growth of technology in recent years brought a lot of contribution in this domain. However it is still challenging task. In this paper we implement Kazakh traditional dance gesture recognition. We use Microsoft Kinect camera to obtain human skeleton and depth information. Then we apply tree-structured Bayesian network and Expectation Maximization algorithm with K-means clustering to calculate conditional linear Gaussians for classifying poses. And finally we use Hidden Markov Model to detect dance gestures. Our main contribution is that we extend Kinect skeleton by adding headwear as a new skeleton joint which is calculated from depth image. This novelty allows us to significantly improve the accuracy of head gesture recognition of a dancer which in turn plays considerable role in whole body gesture recognition. Experimental results show the efficiency of the proposed method and that its performance is comparable to the state-of-the-art system performances.

  14. Characterization of the targeting signal in mitochondrial β-barrel proteins

    PubMed Central

    Jores, Tobias; Klinger, Anna; Groß, Lucia E.; Kawano, Shin; Flinner, Nadine; Duchardt-Ferner, Elke; Wöhnert, Jens; Kalbacher, Hubert; Endo, Toshiya; Schleiff, Enrico; Rapaport, Doron

    2016-01-01

    Mitochondrial β-barrel proteins are synthesized on cytosolic ribosomes and must be specifically targeted to the organelle before their integration into the mitochondrial outer membrane. The signal that assures such precise targeting and its recognition by the organelle remained obscure. In the present study we show that a specialized β-hairpin motif is this long searched for signal. We demonstrate that a synthetic β-hairpin peptide competes with the import of mitochondrial β-barrel proteins and that proteins harbouring a β-hairpin peptide fused to passenger domains are targeted to mitochondria. Furthermore, a β-hairpin motif from mitochondrial proteins targets chloroplast β-barrel proteins to mitochondria. The mitochondrial targeting depends on the hydrophobicity of the β-hairpin motif. Finally, this motif interacts with the mitochondrial import receptor Tom20. Collectively, we reveal that β-barrel proteins are targeted to mitochondria by a dedicated β-hairpin element, and this motif is recognized at the organelle surface by the outer membrane translocase. PMID:27345737

  15. Structural basis of sterol recognition and nonvesicular transport by lipid transfer proteins anchored at membrane contact sites.

    PubMed

    Tong, Junsen; Manik, Mohammad Kawsar; Im, Young Jun

    2018-01-30

    Membrane contact sites (MCSs) in eukaryotic cells are hotspots for lipid exchange, which is essential for many biological functions, including regulation of membrane properties and protein trafficking. Lipid transfer proteins anchored at membrane contact sites (LAMs) contain sterol-specific lipid transfer domains [StARkin domain (SD)] and multiple targeting modules to specific membrane organelles. Elucidating the structural mechanisms of targeting and ligand recognition by LAMs is important for understanding the interorganelle communication and exchange at MCSs. Here, we determined the crystal structures of the yeast Lam6 pleckstrin homology (PH)-like domain and the SDs of Lam2 and Lam4 in the apo form and in complex with ergosterol. The Lam6 PH-like domain displays a unique PH domain fold with a conserved N-terminal α-helix. The Lam6 PH-like domain lacks the basic surface for phosphoinositide binding, but contains hydrophobic patches on its surface, which are critical for targeting to endoplasmic reticulum (ER)-mitochondrial contacts. Structures of the LAM SDs display a helix-grip fold with a hydrophobic cavity and a flexible Ω1-loop as a lid. Ergosterol is bound to the pocket in a head-down orientation, with its hydrophobic acyl group located in the tunnel entrance. The Ω1-loop in an open conformation is essential for ergosterol binding by direct hydrophobic interaction. Structural comparison suggested that the sterol binding mode of the Lam2 SD2 is likely conserved among the sterol transfer proteins of the StARkin superfamily. Structural models of full-length Lam2 correlated with the sterol transport function at the membrane contact sites.

  16. Action recognition in depth video from RGB perspective: A knowledge transfer manner

    NASA Astrophysics Data System (ADS)

    Chen, Jun; Xiao, Yang; Cao, Zhiguo; Fang, Zhiwen

    2018-03-01

    Different video modal for human action recognition has becoming a highly promising trend in the video analysis. In this paper, we propose a method for human action recognition from RGB video to Depth video using domain adaptation, where we use learned feature from RGB videos to do action recognition for depth videos. More specifically, we make three steps for solving this problem in this paper. First, different from image, video is more complex as it has both spatial and temporal information, in order to better encode this information, dynamic image method is used to represent each RGB or Depth video to one image, based on this, most methods for extracting feature in image can be used in video. Secondly, as video can be represented as image, so standard CNN model can be used for training and testing for videos, beside, CNN model can be also used for feature extracting as its powerful feature expressing ability. Thirdly, as RGB videos and Depth videos are belong to two different domains, in order to make two different feature domains has more similarity, domain adaptation is firstly used for solving this problem between RGB and Depth video, based on this, the learned feature from RGB video model can be directly used for Depth video classification. We evaluate the proposed method on one complex RGB-D action dataset (NTU RGB-D), and our method can have more than 2% accuracy improvement using domain adaptation from RGB to Depth action recognition.

  17. User acceptance of intelligent avionics: A study of automatic-aided target recognition

    NASA Technical Reports Server (NTRS)

    Becker, Curtis A.; Hayes, Brian C.; Gorman, Patrick C.

    1991-01-01

    User acceptance of new support systems typically was evaluated after the systems were specified, designed, and built. The current study attempts to assess user acceptance of an Automatic-Aided Target Recognition (ATR) system using an emulation of such a proposed system. The detection accuracy and false alarm level of the ATR system were varied systematically, and subjects rated the tactical value of systems exhibiting different performance levels. Both detection accuracy and false alarm level affected the subjects' ratings. The data from two experiments suggest a cut-off point in ATR performance below which the subjects saw little tactical value in the system. An ATR system seems to have obvious tactical value only if it functions at a correct detection rate of 0.7 or better with a false alarm level of 0.167 false alarms per square degree or fewer.

  18. C1 Domain-Targeted Isophthalate Derivatives Induce Cell Elongation and Cell Cycle Arrest in HeLa Cells

    PubMed Central

    Talman, Virpi; Tuominen, Raimo K.; Gennäs, Gustav Boije af; Yli-Kauhaluoma, Jari; Ekokoski, Elina

    2011-01-01

    Diacylglycerol (DAG)-mediated signaling pathways, such as those mediated by protein kinase C (PKC), are central in regulating cell proliferation and apoptosis. DAG-responsive C1 domains are therefore considered attractive drug targets. Our group has designed a novel class of compounds targeted to the DAG binding site within the C1 domain of PKC. We have previously shown that these 5-(hydroxymethyl)isophthalates modulate PKC activation in living cells. In this study we investigated their effects on HeLa human cervical cancer cell viability and proliferation by using standard cytotoxicity tests and an automated imaging platform with machine vision technology. Cellular effects and their mechanisms were further characterized with the most potent compound, HMI-1a3. Isophthalate derivatives with high affinity to the PKC C1 domain exhibited antiproliferative and non-necrotic cytotoxic effects on HeLa cells. The anti-proliferative effect was irreversible and accompanied by cell elongation. HMI-1a3 induced down-regulation of retinoblastoma protein and cyclins A, B1, D1, and E. Effects of isophthalates on cell morphology, cell proliferation and expression of cell cycle-related proteins were different from those induced by phorbol 12-myristate-13-acetate (PMA) or bryostatin 1, but correlated closely to binding affinities. Therefore, the results strongly indicate that the effect is C1 domain-mediated. PMID:21629792

  19. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity.

    PubMed

    Woodman, Zenda L; Schwager, Sylva L U; Redelinghuys, Pierre; Carmona, Adriana K; Ehlers, Mario R W; Sturrock, Edward D

    2005-08-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the k(cat) for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates.

  20. The N domain of somatic angiotensin-converting enzyme negatively regulates ectodomain shedding and catalytic activity

    PubMed Central

    Woodman, Zenda L.; Schwager, Sylva L. U.; Redelinghuys, Pierre; Carmona, Adriana K.; Ehlers, Mario R. W.; Sturrock, Edward D.

    2005-01-01

    sACE (somatic angiotensin-converting enzyme) consists of two homologous, N and C domains, whereas the testis isoenzyme [tACE (testis ACE)] consists of a single C domain. Both isoenzymes are shed from the cell surface by a sheddase activity, although sACE is shed much less efficiently than tACE. We hypothesize that the N domain of sACE plays a regulatory role, by occluding a recognition motif on the C domain required for ectodomain shedding and by influencing the catalytic efficiency. To test this, we constructed two mutants: CNdom-ACE and CCdom-ACE. CNdom-ACE was shed less efficiently than sACE, whereas CCdom-ACE was shed as efficiently as tACE. Notably, cleavage occurred both within the stalk and the interdomain bridge in both mutants, suggesting that a sheddase recognition motif resides within the C domain and is capable of directly cleaving at both positions. Analysis of the catalytic properties of the mutants and comparison with sACE and tACE revealed that the kcat for sACE and CNdom-ACE was less than or equal to the sum of the kcat values for tACE and the N-domain, suggesting negative co-operativity, whereas the kcat value for the CCdom-ACE suggested positive co-operativity between the two domains. Taken together, the results provide support for (i) the existence of a sheddase recognition motif in the C domain and (ii) molecular flexibility of the N and C domains in sACE, resulting in occlusion of the C-domain recognition motif by the N domain as well as close contact of the two domains during hydrolysis of peptide substrates. PMID:15813703

  1. Phylogenetic analysis and expression profiling of the pattern recognition receptors: Insights into molecular recognition of invading pathogens in Manduca sexta.

    PubMed

    Zhang, Xiufeng; He, Yan; Cao, Xiaolong; Gunaratna, Ramesh T; Chen, Yun-ru; Blissard, Gary; Kanost, Michael R; Jiang, Haobo

    2015-07-01

    Pattern recognition receptors (PRRs) detect microbial pathogens and trigger innate immune responses. Previous biochemical studies have elucidated the physiological functions of eleven PRRs in Manduca sexta but our understanding of the recognition process is still limited, lacking genomic perspectives. While 34 C-type lectin-domain proteins and 16 Toll-like receptors are reported in the companion papers, we present here 120 other putative PRRs identified through the genome annotation. These include 76 leucine-rich repeat (LRR) proteins, 14 peptidoglycan recognition proteins, 6 EGF/Nim-domain proteins, 5 β-1,3-glucanase-related proteins, 4 galectins, 4 fibrinogen-related proteins, 3 thioester proteins, 5 immunoglobulin-domain proteins, 2 hemocytins, and 1 Reeler. Sequence alignment and phylogenetic analysis reveal the evolution history of a diverse repertoire of proteins for pathogen recognition. While functions of insect LRR proteins are mostly unknown, their structure diversification is phenomenal: In addition to the Toll homologs, 22 LRR proteins with a signal peptide are expected to be secreted; 18 LRR proteins lacking signal peptides may be cytoplasmic; 36 LRRs with a signal peptide and a transmembrane segment may be non-Toll receptors on the surface of cells. Expression profiles of the 120 genes in 52 tissue samples reflect complex regulation in various developmental stages and physiological states, including some likely by Rel family transcription factors via κB motifs in the promoter regions. This collection of information is expected to facilitate future biochemical studies detailing their respective roles in this model insect. Copyright © 2015 Elsevier Ltd. All rights reserved.

  2. Linguistic Context Versus Semantic Competition in Word Recognition by Younger and Older Adults With Cochlear Implants.

    PubMed

    Amichetti, Nicole M; Atagi, Eriko; Kong, Ying-Yee; Wingfield, Arthur

    The increasing numbers of older adults now receiving cochlear implants raises the question of how the novel signal produced by cochlear implants may interact with cognitive aging in the recognition of words heard spoken within a linguistic context. The objective of this study was to pit the facilitative effects of a constraining linguistic context against a potential age-sensitive negative effect of response competition on effectiveness of word recognition. Younger (n = 8; mean age = 22.5 years) and older (n = 8; mean age = 67.5 years) adult implant recipients heard 20 target words as the final words in sentences that manipulated the target word's probability of occurrence within the sentence context. Data from published norms were also used to measure response entropy, calculated as the total number of different responses and the probability distribution of the responses suggested by the sentence context. Sentence-final words were presented to participants using a word-onset gating paradigm, in which a target word was presented with increasing amounts of its onset duration in 50 msec increments until the word was correctly identified. Results showed that for both younger and older adult implant users, the amount of word-onset information needed for correct recognition of sentence-final words was inversely proportional to their likelihood of occurrence within the sentence context, with older adults gaining differential advantage from the contextual constraints offered by a sentence context. On the negative side, older adults' word recognition was differentially hampered by high response entropy, with this effect being driven primarily by the number of competing responses that might also fit the sentence context. Consistent with previous research with normal-hearing younger and older adults, the present results showed older adult implant users' recognition of spoken words to be highly sensitive to linguistic context. This sensitivity, however, also resulted in a

  3. The PYRIN domain: A member of the death domain-fold superfamily

    PubMed Central

    Fairbrother, Wayne J.; Gordon, Nathaniel C.; Humke, Eric W.; O'Rourke, Karen M.; Starovasnik, Melissa A.; Yin, Jian-Ping; Dixit, Vishva M.

    2001-01-01

    PYRIN domains were identified recently as putative protein–protein interaction domains at the N-termini of several proteins thought to function in apoptotic and inflammatory signaling pathways. The ∼95 residue PYRIN domains have no statistically significant sequence homology to proteins with known three-dimensional structure. Using secondary structure prediction and potential-based fold recognition methods, however, the PYRIN domain is predicted to be a member of the six-helix bundle death domain-fold superfamily that includes death domains (DDs), death effector domains (DEDs), and caspase recruitment domains (CARDs). Members of the death domain-fold superfamily are well established mediators of protein–protein interactions found in many proteins involved in apoptosis and inflammation, indicating further that the PYRIN domains serve a similar function. An homology model of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1, a member of the Apaf-1/Ced-4 family of proteins, was constructed using the three-dimensional structures of the FADD and p75 neurotrophin receptor DDs, and of the Apaf-1 and caspase-9 CARDs, as templates. Validation of the model using a variety of computational techniques indicates that the fold prediction is consistent with the sequence. Comparison of a circular dichroism spectrum of the PYRIN domain of CARD7/DEFCAP/NAC/NALP1 with spectra of several proteins known to adopt the death domain-fold provides experimental support for the structure prediction. PMID:11514682

  4. Application of Wavelet Transform for PDZ Domain Classification

    PubMed Central

    Daqrouq, Khaled; Alhmouz, Rami; Balamesh, Ahmed; Memic, Adnan

    2015-01-01

    PDZ domains have been identified as part of an array of signaling proteins that are often unrelated, except for the well-conserved structural PDZ domain they contain. These domains have been linked to many disease processes including common Avian influenza, as well as very rare conditions such as Fraser and Usher syndromes. Historically, based on the interactions and the nature of bonds they form, PDZ domains have most often been classified into one of three classes (class I, class II and others - class III), that is directly dependent on their binding partner. In this study, we report on three unique feature extraction approaches based on the bigram and trigram occurrence and existence rearrangements within the domain's primary amino acid sequences in assisting PDZ domain classification. Wavelet packet transform (WPT) and Shannon entropy denoted by wavelet entropy (WE) feature extraction methods were proposed. Using 115 unique human and mouse PDZ domains, the existence rearrangement approach yielded a high recognition rate (78.34%), which outperformed our occurrence rearrangements based method. The recognition rate was (81.41%) with validation technique. The method reported for PDZ domain classification from primary sequences proved to be an encouraging approach for obtaining consistent classification results. We anticipate that by increasing the database size, we can further improve feature extraction and correct classification. PMID:25860375

  5. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets

    PubMed Central

    Noujaim, Sami F.; Stuckey, Jeanne A.; Ponce-Balbuena, Daniela; Ferrer-Villada, Tania; López-Izquierdo, Angelica; Pandit, Sandeep; Calvo, Conrado J.; Grzeda, Krzysztof R.; Berenfeld, Omer; Sánchez Chapula, José A.; Jalife, José

    2010-01-01

    Atrial and ventricular tachyarrhythmias can be perpetuated by up-regulation of inward rectifier potassium channels. Thus, it may be beneficial to block inward rectifier channels under conditions in which their function becomes arrhythmogenic (e.g., inherited gain-of-function mutation channelopathies, ischemia, and chronic and vagally mediated atrial fibrillation). We hypothesize that the antimalarial quinoline chloroquine exerts potent antiarrhythmic effects by interacting with the cytoplasmic domains of Kir2.1 (IK1), Kir3.1 (IKACh), or Kir6.2 (IKATP) and reducing inward rectifier potassium currents. In isolated hearts of three different mammalian species, intracoronary chloroquine perfusion reduced fibrillatory frequency (atrial or ventricular), and effectively terminated the arrhythmia with resumption of sinus rhythm. In patch-clamp experiments chloroquine blocked IK1, IKACh, and IKATP. Comparative molecular modeling and ligand docking of chloroquine in the intracellular domains of Kir2.1, Kir3.1, and Kir6.2 suggested that chloroquine blocks or reduces potassium flow by interacting with negatively charged amino acids facing the ion permeation vestibule of the channel in question. These results open a novel path toward discovering antiarrhythmic pharmacophores that target specific residues of the cytoplasmic domain of inward rectifier potassium channels.—Noujaim, S. F., Stuckey, J. A., Ponce-Balbuena, D., Ferrer-Villada, T., López-Izquierdo, A., Pandit, S., Calvo, C. J., Grzeda, K. R., Berenfeld, O., Sánchez Chapula, J. A., Jalife, J. Specific residues of the cytoplasmic domains of cardiac inward rectifier potassium channels are effective antifibrillatory targets. PMID:20585026

  6. Allosteric response and substrate sensitivity in peptide binding of the signal recognition particle.

    PubMed

    Wang, Connie Y; Miller, Thomas F

    2014-10-31

    We characterize the conformational dynamics and substrate selectivity of the signal recognition particle (SRP) using a thermodynamic free energy cycle approach and microsecond timescale molecular dynamics simulations. The SRP is a central component of the co-translational protein targeting machinery that binds to the N-terminal signal peptide (SP) of nascent proteins. We determined the shift in relative conformational stability of the SRP upon substrate binding to quantify allosteric coupling between SRP domains. In particular, for dipeptidyl aminopeptidase, an SP that is recognized by the SRP for co-translational targeting, it is found that substrate binding induces substantial changes in the SRP toward configurations associated with targeting of the nascent protein, and it is found that the changes are modestly enhanced by a mutation that increases the hydrophobicity of the SP. However, for alkaline phosphatase, an SP that is recognized for post-translational targeting, substrate binding induces the reverse change in the SRP conformational distribution away from targeting configurations. Microsecond timescale trajectories reveal the intrinsic flexibility of the SRP conformational landscape and provide insight into recent single molecule studies by illustrating that 10-nm lengthscale changes between FRET pairs occur via the rigid-body movement of SRP domains connected by the flexible linker region. In combination, these results provide direct evidence for the hypothesis that substrate-controlled conformational switching in the SRP provides a mechanism for discriminating between different SPs and for connecting substrate binding to downstream steps in the protein targeting pathway. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. Domain-Generality of Timing-Based Serial Order Processes in Short-Term Memory: New Insights from Musical and Verbal Domains

    PubMed Central

    Kowialiewski, Benjamin; Majerus, Steve

    2016-01-01

    Several models in the verbal domain of short-term memory (STM) consider a dissociation between item and order processing. This view is supported by data demonstrating that different types of time-based interference have a greater effect on memory for the order of to-be-remembered items than on memory for the items themselves. The present study investigated the domain-generality of the item versus serial order dissociation by comparing the differential effects of time-based interfering tasks, such as rhythmic interference and articulatory suppression, on item and order processing in verbal and musical STM domains. In Experiment 1, participants had to maintain sequences of verbal or musical information in STM, followed by a probe sequence, this under different conditions of interference (no-interference, rhythmic interference, articulatory suppression). They were required to decide whether all items of the probe list matched those of the memory list (item condition) or whether the order of the items in the probe sequence matched the order in the memory list (order condition). In Experiment 2, participants performed a serial order probe recognition task for verbal and musical sequences ensuring sequential maintenance processes, under no-interference or rhythmic interference conditions. For Experiment 1, serial order recognition was not significantly more impacted by interfering tasks than was item recognition, this for both verbal and musical domains. For Experiment 2, we observed selective interference of the rhythmic interference condition on both musical and verbal order STM tasks. Overall, the results suggest a similar and selective sensitivity to time-based interference for serial order STM in verbal and musical domains, but only when the STM tasks ensure sequential maintenance processes. PMID:27992565

  8. Domain-Generality of Timing-Based Serial Order Processes in Short-Term Memory: New Insights from Musical and Verbal Domains.

    PubMed

    Gorin, Simon; Kowialiewski, Benjamin; Majerus, Steve

    2016-01-01

    Several models in the verbal domain of short-term memory (STM) consider a dissociation between item and order processing. This view is supported by data demonstrating that different types of time-based interference have a greater effect on memory for the order of to-be-remembered items than on memory for the items themselves. The present study investigated the domain-generality of the item versus serial order dissociation by comparing the differential effects of time-based interfering tasks, such as rhythmic interference and articulatory suppression, on item and order processing in verbal and musical STM domains. In Experiment 1, participants had to maintain sequences of verbal or musical information in STM, followed by a probe sequence, this under different conditions of interference (no-interference, rhythmic interference, articulatory suppression). They were required to decide whether all items of the probe list matched those of the memory list (item condition) or whether the order of the items in the probe sequence matched the order in the memory list (order condition). In Experiment 2, participants performed a serial order probe recognition task for verbal and musical sequences ensuring sequential maintenance processes, under no-interference or rhythmic interference conditions. For Experiment 1, serial order recognition was not significantly more impacted by interfering tasks than was item recognition, this for both verbal and musical domains. For Experiment 2, we observed selective interference of the rhythmic interference condition on both musical and verbal order STM tasks. Overall, the results suggest a similar and selective sensitivity to time-based interference for serial order STM in verbal and musical domains, but only when the STM tasks ensure sequential maintenance processes.

  9. Direct recognition of superparamagnetic nanocrystals by macrophage scavenger receptor SR-AI.

    PubMed

    Chao, Ying; Karmali, Priya P; Mukthavaram, Rajesh; Kesari, Santosh; Kouznetsova, Valentina L; Tsigelny, Igor F; Simberg, Dmitri

    2013-05-28

    Scavenger receptors (SRs) are molecular pattern recognition receptors that have been shown to mediate opsonin-independent uptake of therapeutic and imaging nanoparticles, underlying the importance of SRs in nanomedicine. Unlike pathogens, engineered nanomaterials offer great flexibility in control of surface properties, allowing addressing specific questions regarding the molecular mechanisms of nanoparticle recognition. Recently, we showed that SR-type AI/II mediates opsonin-independent internalization of dextran superparamagnetic iron oxide (SPIO) nanoparticles via positively charged extracellular collagen-like domain. To understand the mechanism of opsonin-independent SPIO recognition, we tested the binding and uptake of nanoparticles with different surface coatings by SR-AI. SPIO coated with 10 kDa dextran was efficiently recognized and taken up by SR-AI transfected cells and J774 macrophages, while SPIO with 20 kDa dextran coating or cross-linked dextran hydrogel avoided the binding and uptake. Nanoparticle negative charge density and zeta-potential did not correlate with SR-AI binding/uptake efficiency. Additional experiments and computer modeling revealed that recognition of the iron oxide crystalline core by the positively charged collagen-like domain of SR-AI is sterically hindered by surface polymer coating. Importantly, the modeling revealed a strong complementarity between the surface Fe-OH groups of the magnetite crystal and the charged lysines of the collagen-like domain of SR-AI, suggesting a specific recognition of SPIO crystalline surface. These data provide an insight into the molecular recognition of nanocrystals by innate immunity receptors and the mechanisms whereby polymer coatings promote immune evasion.

  10. Hyaluronan functionalizing QDs as turn-on fluorescent probe for targeted recognition CD44 receptor

    NASA Astrophysics Data System (ADS)

    Zhou, Shang; Huo, Danqun; Hou, Changjun; Yang, Mei; Fa, Huanbao

    2017-09-01

    The recognition of tumor markers in living cancer cells has attracted increasing interest. In the present study, the turn-on fluorescence probe was designed based on the fluorescence of thiolated chitosan-coated CdTe QDs (CdTe/TCS QDs) quenched by hyaluronan, which could provide the low background signal for sensitive cellular imaging. This system is expected to offer specific recognition of CD44 receptor over other substances owing to the specific affinity of hyaluronan and CD44 receptor ( 8-9 kcal/mol). The probe is stable in aqueous and has little toxicity to living cells; thus, it can be utilized for targeted cancer cell imaging. The living lung cancer cell imaging experiments further demonstrate its value in recognizing cell-surface CD44 receptor with turn-on mode. In addition, the probe can be used to recognize and differentiate the subtypes of lung cancer cells based on the difference of CD44 expression on the surface of lung cancer cells. And, the western blot test further confirmed that the expression level of the CD44 receptor in lung cancer cells is different. Therefore, this probe may be potentially applied in recognizing lung cancer cells with higher contrast and sensitivity and provide new tools for cancer prognosis and therapy. [Figure not available: see fulltext.

  11. WW Domains of the Yes-Kinase-Associated-Protein (YAP) Transcriptional Regulator Behave as Independent Units with Different Binding Preferences for PPxY Motif-Containing Ligands

    PubMed Central

    Iglesias-Bexiga, Manuel; Castillo, Francisco; Cobos, Eva S.; Oka, Tsutomu; Sudol, Marius; Luque, Irene

    2015-01-01

    YAP is a WW domain-containing effector of the Hippo tumor suppressor pathway, and the object of heightened interest as a potent oncogene and stemness factor. YAP has two major isoforms that differ in the number of WW domains they harbor. Elucidating the degree of co-operation between these WW domains is important for a full understanding of the molecular function of YAP. We present here a detailed biophysical study of the structural stability and binding properties of the two YAP WW domains aimed at investigating the relationship between both domains in terms of structural stability and partner recognition. We have carried out a calorimetric study of the structural stability of the two YAP WW domains, both isolated and in a tandem configuration, and their interaction with a set of functionally relevant ligands derived from PTCH1 and LATS kinases. We find that the two YAP WW domains behave as independent units with different binding preferences, suggesting that the presence of the second WW domain might contribute to modulate target recognition between the two YAP isoforms. Analysis of structural models and phage-display studies indicate that electrostatic interactions play a critical role in binding specificity. Together, these results are relevant to understand of YAP function and open the door to the design of highly specific ligands of interest to delineate the functional role of each WW domain in YAP signaling. PMID:25607641

  12. Structural basis for recognition of the T cell adaptor protein SLP-76 by the SH3 domain of phospholipase Cgamma1.

    PubMed

    Deng, Lu; Velikovsky, C Alejandro; Swaminathan, Chittoor P; Cho, Sangwoo; Mariuzza, Roy A

    2005-09-09

    The enzyme phospholipase Cgamma1 (PLCgamma1) is essential for T cell signaling and activation. Following T cell receptor ligation, PLCgamma1 interacts through its SH2 and SH3 domains with the adaptors LAT and SLP-76, respectively, to form a multiprotein signaling complex that leads to activation of PLCgamma1 by Syk tyrosine kinases. To identify the binding site for PLCgamma1 in SLP-76, we used isothermal titration calorimetry to measure affinities for the interaction of PLCgamma1-SH3 with a set of overlapping peptides spanning the central proline-rich region of SLP-76. PLCgamma1-SH3 bound with high specificity to the SLP-76 motif 186PPVPPQRP193, which represents the minimal binding site. To understand the basis for selective recognition, we determined the crystal structures of PLCgamma1-SH3 in free form, and bound to a 10-mer peptide containing this site, to resolutions of 1.60 A and 1.81 A, respectively. The structures reveal that several key contacting residues of the SH3 shift toward the SLP-76 peptide upon complex formation, optimizing the fit and strengthening hydrophobic interactions. Selectivity results mainly from strict shape complementarity between protein and peptide, rather than sequence-specific hydrogen bonding. In addition, Pro193 of SLP-76 assists in positioning Arg192 into the compass pocket of PLCgamma1-SH3, which coordinates the compass residue through an unusual aspartate. The PLCgamma1-SH3/SLP-76 structure provides insights into ligand binding by SH3 domains related to PLCgamma1-SH3, as well as into recognition by PLCgamma1 of signaling partners other than SLP-76.

  13. A novel C-type lectin with two CRD domains from Chinese shrimp Fenneropenaeus chinensis functions as a pattern recognition protein.

    PubMed

    Zhang, Xiao-Wen; Xu, Wen-Teng; Wang, Xian-Wei; Mu, Yi; Zhao, Xiao-Fan; Yu, Xiao-Qiang; Wang, Jin-Xing

    2009-05-01

    Lectins are regarded as potential immune recognition proteins. In this study, a novel C-type lectin (Fc-Lec2) was cloned from the hepatopancreas of Chinese shrimp, Fenneropenaeus chinensis. The cDNA of Fc-Lec2 is 1219 bp with an open reading frame (ORF) of 1002 bp that encodes a protein of 333 amino acids. Fc-Lec2 contains a signal peptide and two different carbohydrate recognition domains (CRDs) arranged in tandem. The first CRD contains a QPD (Gln-Pro-Asp) motif that has a predicted binding specificity for galactose and the second CRD contains a EPN (Glu-Pro-Asn) motif for mannose. Fc-Lec2 was constitutively expressed in the hepatopancreas of normal shrimp, and its expression was up-regulated in the hepatopancreas of shrimp challenged with bacteria or viruses. Recombinant mature Fc-Lec2 and its two individual CRDs (CRD1 and 2) did not have hemagglutinating activity against animal red blood cells, but agglutinated some gram-positive and gram-negative bacteria in a calcium-dependent manner. The three recombinant proteins also bound to bacteria in the absence of calcium. Fc-Lec2 seems to have broader specificity and higher affinity for bacteria and polysaccharides (peptidoglycan, lipoteichoic acid and lipopolysaccharide) than each of the two individual CRDs. These data suggest that the two CRDs have synergistic effect, and the intact lectin may be more effective in response to bacterial infection, the Fc-Lec2 performs its pattern recognition function by binding to polysaccharides of pathogen cells.

  14. Does aging impair first impression accuracy? Differentiating emotion recognition from complex social inferences.

    PubMed

    Krendl, Anne C; Rule, Nicholas O; Ambady, Nalini

    2014-09-01

    Young adults can be surprisingly accurate at making inferences about people from their faces. Although these first impressions have important consequences for both the perceiver and the target, it remains an open question whether first impression accuracy is preserved with age. Specifically, could age differences in impressions toward others stem from age-related deficits in accurately detecting complex social cues? Research on aging and impression formation suggests that young and older adults show relative consensus in their first impressions, but it is unknown whether they differ in accuracy. It has been widely shown that aging disrupts emotion recognition accuracy, and that these impairments may predict deficits in other social judgments, such as detecting deceit. However, it is unclear whether general impression formation accuracy (e.g., emotion recognition accuracy, detecting complex social cues) relies on similar or distinct mechanisms. It is important to examine this question to evaluate how, if at all, aging might affect overall accuracy. Here, we examined whether aging impaired first impression accuracy in predicting real-world outcomes and categorizing social group membership. Specifically, we studied whether emotion recognition accuracy and age-related cognitive decline (which has been implicated in exacerbating deficits in emotion recognition) predict first impression accuracy. Our results revealed that emotion recognition accuracy did not predict first impression accuracy, nor did age-related cognitive decline impair it. These findings suggest that domains of social perception outside of emotion recognition may rely on mechanisms that are relatively unimpaired by aging. PsycINFO Database Record (c) 2014 APA, all rights reserved.

  15. Engineering domain fusion chimeras from I-OnuI family LAGLIDADG homing endonucleases

    PubMed Central

    Lambert, Abigail R.; Kuhar, Ryan; Jarjour, Jordan; Kulshina, Nadia; Parmeggiani, Fabio; Danaher, Patrick; Gano, Jacob; Baker, David; Stoddard, Barry L.; Scharenberg, Andrew M.

    2012-01-01

    Although engineered LAGLIDADG homing endonucleases (LHEs) are finding increasing applications in biotechnology, their generation remains a challenging, industrial-scale process. As new single-chain LAGLIDADG nuclease scaffolds are identified, however, an alternative paradigm is emerging: identification of an LHE scaffold whose native cleavage site is a close match to a desired target sequence, followed by small-scale engineering to modestly refine recognition specificity. The application of this paradigm could be accelerated if methods were available for fusing N- and C-terminal domains from newly identified LHEs into chimeric enzymes with hybrid cleavage sites. Here we have analyzed the structural requirements for fusion of domains extracted from six single-chain I-OnuI family LHEs, spanning 40–70% amino acid identity. Our analyses demonstrate that both the LAGLIDADG helical interface residues and the linker peptide composition have important effects on the stability and activity of chimeric enzymes. Using a simple domain fusion method in which linker peptide residues predicted to contact their respective domains are retained, and in which limited variation is introduced into the LAGLIDADG helix and nearby interface residues, catalytically active enzymes were recoverable for ∼70% of domain chimeras. This method will be useful for creating large numbers of chimeric LHEs for genome engineering applications. PMID:22684507

  16. Human target acquisition performance

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  17. Aptamer Recognition of Multiplexed Small-Molecule-Functionalized Substrates.

    PubMed

    Nakatsuka, Nako; Cao, Huan H; Deshayes, Stephanie; Melkonian, Arin Lucy; Kasko, Andrea M; Weiss, Paul S; Andrews, Anne M

    2018-05-31

    Aptamers are chemically synthesized oligonucleotides or peptides with molecular recognition capabilities. We investigated recognition of substrate-tethered small-molecule targets, using neurotransmitters as examples, and fluorescently labeled DNA aptamers. Substrate regions patterned via microfluidic channels with dopamine or L-tryptophan were selectively recognized by previously identified dopamine or L-tryptophan aptamers, respectively. The on-substrate dissociation constant determined for the dopamine aptamer was comparable to, though slightly greater than the previously determined solution dissociation constant. Using pre-functionalized neurotransmitter-conjugated oligo(ethylene glycol) alkanethiols and microfluidics patterning, we produced multiplexed substrates to capture and to sort aptamers. Substrates patterned with L-DOPA, L-DOPS, and L-5-HTP enabled comparison of the selectivity of the dopamine aptamer for different targets via simultaneous determination of in situ binding constants. Thus, beyond our previous demonstrations of recognition by protein binding partners (i.e., antibodies and G-protein-coupled receptors), strategically optimized small-molecule-functionalized substrates show selective recognition of nucleic acid binding partners. These substrates are useful for side-by-side target comparisons, and future identification and characterization of novel aptamers targeting neurotransmitters or other important small-molecules.

  18. Prefrontal contributions to domain-general executive control processes during temporal context retrieval.

    PubMed

    Rajah, M Natasha; Ames, Blaine; D'Esposito, Mark

    2008-03-07

    Neuroimaging studies have reported increased prefrontal cortex (PFC) activity during temporal context retrieval versus recognition memory. However, it remains unclear if these activations reflect PFC contributions to domain-general executive control processes or domain-specific retrieval processes. To gain a better understanding of the functional roles of these various PFC regions during temporal context retrieval we propose it is necessary to examine PFC activity across tasks from different domains, in which parallel manipulations are included targeting specific cognitive processes. In the current fMRI study, we examined domain-general and domain-specific PFC contributions to temporal context retrieval by increasing stimulus (but maintaining response number) and increasing response number (but maintaining stimulus number) across temporal context memory and ordering control tasks, for faces. The control task required subjects to order faces from youngest to oldest. Our behavioral results indicate that the combination of increased stimulus and response numbers significantly increased task difficulty for temporal context retrieval and ordering tasks. Across domains, increasing stimulus number, while maintaining response numbers, caused greater right lateral premotor cortex (BA 6/8) activity; whereas increasing response number, while maintaining stimulus number, caused greater domain-general left DLPFC (BA 9) and VLPFC (BA 44/45) activity. In addition, we found domain-specific right DLPFC (BA 9) activity only during retrieval events. These results highlight the functional heterogeneity of frontal cortex, and suggest its involvement in temporal context retrieval is related to its role in various cognitive control processes.

  19. Infrared maritime target detection using a probabilistic single Gaussian model of sea clutter in Fourier domain

    NASA Astrophysics Data System (ADS)

    Zhou, Anran; Xie, Weixin; Pei, Jihong; Chen, Yapei

    2018-02-01

    For ship targets detection in cluttered infrared image sequences, a robust detection method, based on the probabilistic single Gaussian model of sea background in Fourier domain, is put forward. The amplitude spectrum sequences at each frequency point of the pure seawater images in Fourier domain, being more stable than the gray value sequences of each background pixel in the spatial domain, are regarded as a Gaussian model. Next, a probability weighted matrix is built based on the stability of the pure seawater's total energy spectrum in the row direction, to make the Gaussian model more accurate. Then, the foreground frequency points are separated from the background frequency points by the model. Finally, the false-alarm points are removed utilizing ships' shape features. The performance of the proposed method is tested by visual and quantitative comparisons with others.

  20. Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding Domain I in mismatch recognition.

    PubMed Central

    Lee, Susan D.; Surtees, Jennifer A.; Alani, Eric

    2007-01-01

    In eukaryotic mismatch repair (MMR) MSH2-MSH6 initiates the repair of base-base and small insertion/deletion mismatches while MSH2-MSH3 repairs larger insertion/deletion mismatches. In this study we showed that the msh2Δ1 mutation, containing a complete deletion of the conserved mismatch recognition Domain I of MSH2, conferred a separation of function phenotype with respect to MSH2-MSH3 and MSH2-MSH6 functions. Strains bearing the msh2Δ1 mutation were nearly wild-type in MSH2-MSH6-mediated MMR and in suppressing recombination between DNA sequences predicted to form mismatches recognized by MSH2-MSH6. However, these strains were completely defective in MSH2-MSH3-mediated MMR and recombination functions. This information encouraged us to analyze the contributions of Domain I to the mismatch binding specificity of MSH2-MSH3 in genetic and biochemical assays. We found that Domain I in MSH2 contributed a non-specific DNA binding activity while Domain I of MSH3 appeared important for mismatch binding specificity and for suppressing non-specific DNA-binding. These observations reveal distinct requirements for the MSH2 DNA binding Domain I in the repair of DNA mismatches and suggest that the binding of MSH2-MSH3 to mismatch DNA involves protein-DNA contacts that appear very different from those required for MSH2-MSH6 mismatch binding. PMID:17157869

  1. Saccharomyces cerevisiae MSH2-MSH3 and MSH2-MSH6 complexes display distinct requirements for DNA binding domain I in mismatch recognition.

    PubMed

    Lee, Susan D; Surtees, Jennifer A; Alani, Eric

    2007-02-09

    In eukaryotic mismatch repair (MMR) MSH2-MSH6 initiates the repair of base-base and small insertion/deletion mismatches while MSH2-MSH3 repairs larger insertion/deletion mismatches. Here, we show that the msh2Delta1 mutation, containing a complete deletion of the conserved mismatch recognition domain I of MSH2, conferred a separation of function phenotype with respect to MSH2-MSH3 and MSH2-MSH6 functions. Strains bearing the msh2Delta1 mutation were nearly wild-type in MSH2-MSH6-mediated MMR and in suppressing recombination between DNA sequences predicted to form mismatches recognized by MSH2-MSH6. However, these strains were completely defective in MSH2-MSH3-mediated MMR and recombination functions. This information encouraged us to analyze the contributions of domain I to the mismatch binding specificity of MSH2-MSH3 in genetic and biochemical assays. We found that domain I in MSH2 contributed a non-specific DNA binding activity while domain I of MSH3 appeared important for mismatch binding specificity and for suppressing non-specific DNA binding. These observations reveal distinct requirements for the MSH2 DNA binding domain I in the repair of DNA mismatches and suggest that the binding of MSH2-MSH3 to mismatch DNA involves protein-DNA contacts that appear very different from those required for MSH2-MSH6 mismatch binding.

  2. Structure of the SH3 Domain of Rat Endophilin A2

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

    Loll,P.; Swain, E.; Chen, Y.

    2008-01-01

    The crystal structure of the SH3 domain of rat endophilin A2 has been determined by the multiwavelength anomalous dispersion method and refined at a resolution of 1.70 Angstroms to R and Rfree values of 0.196 and 0.217, respectively. The structure adheres to the canonical SH3-domain fold and is highly similar to those of the corresponding domains of endophilins A1 and A3. An intermolecular packing interaction between two molecules in the lattice exploits features that are commonly observed in SH3-domain ligand recognition, including the insertion of a proline side chain into the ligand-binding groove of the protein and the recognition ofmore » a basic residue by a cluster of acidic side chains on the RT loop.« less

  3. Integration of decoy domains derived from protein targets of pathogen effectors into plant immune receptors is widespread.

    PubMed

    Kroj, Thomas; Chanclud, Emilie; Michel-Romiti, Corinne; Grand, Xavier; Morel, Jean-Benoit

    2016-04-01

    Plant immune receptors of the class of nucleotide-binding and leucine-rich repeat domain (NLR) proteins can contain additional domains besides canonical NB-ARC (nucleotide-binding adaptor shared by APAF-1, R proteins, and CED-4 (NB-ARC)) and leucine-rich repeat (LRR) domains. Recent research suggests that these additional domains act as integrated decoys recognizing effectors from pathogens. Proteins homologous to integrated decoys are suspected to be effector targets and involved in disease or resistance. Here, we scrutinized 31 entire plant genomes to identify putative integrated decoy domains in NLR proteins using the Interpro search. The involvement of the Zinc Finger-BED type (ZBED) protein containing a putative decoy domain, called BED, in rice (Oryza sativa) resistance was investigated by evaluating susceptibility to the blast fungus Magnaporthe oryzae in rice over-expression and knock-out mutants. This analysis showed that all plants tested had integrated various atypical protein domains into their NLR proteins (on average 3.5% of all NLR proteins). We also demonstrated that modifying the expression of the ZBED gene modified disease susceptibility. This study suggests that integration of decoy domains in NLR immune receptors is widespread and frequent in plants. The integrated decoy model is therefore a powerful concept to identify new proteins involved in disease resistance. Further in-depth examination of additional domains in NLR proteins promises to unravel many new proteins of the plant immune system. © 2016 The Authors. New Phytologist © 2016 New Phytologist Trust.

  4. Crystal structure of ryanodine receptor N-terminal domain from Plutella xylostella reveals two potential species-specific insecticide-targeting sites.

    PubMed

    Lin, Lianyun; Liu, Chen; Qin, Juan; Wang, Jie; Dong, Shengjie; Chen, Wei; He, Weiyi; Gao, Qingzhi; You, Minsheng; Yuchi, Zhiguang

    2018-01-01

    Ryanodine receptors (RyRs) are large calcium-release channels located in sarcoplasmic reticulum membrane. They play a central role in excitation-contraction coupling of muscle cells. Three commercialized insecticides targeting pest RyRs generate worldwide sales over 2 billion U.S. dollars annually, but the structure of insect RyRs remains elusive, hindering our understanding of the mode of action of RyR-targeting insecticides and the development of insecticide resistance in pests. Here we present the crystal structure of RyR N-terminal domain (NTD) (residue 1-205) at 2.84 Å resolution from the diamondback moth (DBM), Plutella xylostella, a destructive pest devouring cruciferous crops all over the world. Similar to its mammalian homolog, DBM RyR NTD consists of a beta-trefoil folding motif and a flanking alpha helix. Interestingly, two regions in NTD interacting with neighboring domains showed distinguished conformations in DBM relative to mammalian RyRs. Using homology modeling and molecular dynamics simulation, we created a structural model of the N-terminal three domains, showing two unique binding pockets that could be targeted by potential species-specific insecticides. Thermal melt experiment showed that the stability of DBM RyR NTD was higher than mammalian RyRs, probably due to a stable intra-domain disulfide bond observed in the crystal structure. Previously DBM NTD was shown to be one of the two critical regions to interact with insecticide flubendiamide, but isothermal titration calorimetry experiments negated DBM NTD alone as a major binding site for flubendiamide. Copyright © 2017 Elsevier Ltd. All rights reserved.

  5. Challenging ocular image recognition

    NASA Astrophysics Data System (ADS)

    Pauca, V. Paúl; Forkin, Michael; Xu, Xiao; Plemmons, Robert; Ross, Arun A.

    2011-06-01

    Ocular recognition is a new area of biometric investigation targeted at overcoming the limitations of iris recognition performance in the presence of non-ideal data. There are several advantages for increasing the area beyond the iris, yet there are also key issues that must be addressed such as size of the ocular region, factors affecting performance, and appropriate corpora to study these factors in isolation. In this paper, we explore and identify some of these issues with the goal of better defining parameters for ocular recognition. An empirical study is performed where iris recognition methods are contrasted with texture and point operators on existing iris and face datasets. The experimental results show a dramatic recognition performance gain when additional features are considered in the presence of poor quality iris data, offering strong evidence for extending interest beyond the iris. The experiments also highlight the need for the direct collection of additional ocular imagery.

  6. Functional recognition of the modified human tRNALys3(UUU) anticodon domain by HIV's nucleocapsid protein and a peptide mimic.

    PubMed

    Graham, William D; Barley-Maloney, Lise; Stark, Caren J; Kaur, Amarpreet; Stolarchuk, Christina; Stolyarchuk, Khrystyna; Sproat, Brian; Leszczynska, Grazyna; Malkiewicz, Andrzej; Safwat, Nedal; Mucha, Piotr; Guenther, Richard; Agris, Paul F

    2011-07-22

    The HIV-1 nucleocapsid protein, NCp7, facilitates the use of human tRNA(Lys3)(UUU) as the primer for reverse transcription. NCp7 also remodels the htRNA's amino acid accepting stem and anticodon domains in preparation for their being annealed to the viral genome. To understand the possible influence of the htRNA's unique composition of post-transcriptional modifications on NCp7 recognition of htRNA(Lys3)(UUU), the protein's binding and functional remodeling of the human anticodon stem and loop domain (hASL(Lys3)) were studied. NCp7 bound the hASL(Lys3)(UUU) modified with 5-methoxycarbonylmethyl-2-thiouridine at position-34 (mcm(5)s(2)U(34)) and 2-methylthio-N(6)-threonylcarbamoyladenosine at position-37 (ms(2)t(6)A(37)) with a considerably higher affinity than the unmodified hASL(Lys3)(UUU) (K(d)=0.28±0.03 and 2.30±0.62 μM, respectively). NCp7 denatured the structure of the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) more effectively than that of the unmodified hASL(Lys3)(UUU). Two 15 amino acid peptides selected from phage display libraries demonstrated a high affinity (average K(d)=0.55±0.10 μM) and specificity for the ASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37) comparable to that of NCp7. The peptides recognized a t(6)A(37)-modified ASL with an affinity (K(d)=0.60±0.09 μM) comparable to that for hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37), indicating a preference for the t(6)A(37) modification. Significantly, one of the peptides was capable of relaxing the hASL(Lys3)(UUU)-mcm(5)s(2)U(34);ms(2)t(6)A(37);Ψ(39) structure in a manner similar to that of NCp7, and therefore could be used to further study protein recognition of RNA modifications. The post-transcriptional modifications of htRNA(Lys3)(UUU) have been found to be important determinants of NCp7's recognition prior to the tRNA(Lys3)(UUU) being annealed to the viral genome as the primer of reverse transcription. Copyright © 2011 Elsevier Ltd. All rights reserved.

  7. A Kinect based sign language recognition system using spatio-temporal features

    NASA Astrophysics Data System (ADS)

    Memiş, Abbas; Albayrak, Songül

    2013-12-01

    This paper presents a sign language recognition system that uses spatio-temporal features on RGB video images and depth maps for dynamic gestures of Turkish Sign Language. Proposed system uses motion differences and accumulation approach for temporal gesture analysis. Motion accumulation method, which is an effective method for temporal domain analysis of gestures, produces an accumulated motion image by combining differences of successive video frames. Then, 2D Discrete Cosine Transform (DCT) is applied to accumulated motion images and temporal domain features transformed into spatial domain. These processes are performed on both RGB images and depth maps separately. DCT coefficients that represent sign gestures are picked up via zigzag scanning and feature vectors are generated. In order to recognize sign gestures, K-Nearest Neighbor classifier with Manhattan distance is performed. Performance of the proposed sign language recognition system is evaluated on a sign database that contains 1002 isolated dynamic signs belongs to 111 words of Turkish Sign Language (TSL) in three different categories. Proposed sign language recognition system has promising success rates.

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

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

  9. Multiple conformations of the cytidine repressor DNA-binding domain coalesce to one upon recognition of a specific DNA surface.

    PubMed

    Moody, Colleen L; Tretyachenko-Ladokhina, Vira; Laue, Thomas M; Senear, Donald F; Cocco, Melanie J

    2011-08-09

    The cytidine repressor (CytR) is a member of the LacR family of bacterial repressors with distinct functional features. The Escherichia coli CytR regulon comprises nine operons whose palindromic operators vary in both sequence and, most significantly, spacing between the recognition half-sites. This suggests a strong likelihood that protein folding would be coupled to DNA binding as a mechanism to accommodate the variety of different operator architectures to which CytR is targeted. Such coupling is a common feature of sequence-specific DNA-binding proteins, including the LacR family repressors; however, there are no significant structural rearrangements upon DNA binding within the three-helix DNA-binding domains (DBDs) studied to date. We used nuclear magnetic resonance (NMR) spectroscopy to characterize the CytR DBD free in solution and to determine the high-resolution structure of a CytR DBD monomer bound specifically to one DNA half-site of the uridine phosphorylase (udp) operator. We find that the free DBD populates multiple distinct conformations distinguished by up to four sets of NMR peaks per residue. This structural heterogeneity is previously unknown in the LacR family. These stable structures coalesce into a single, more stable udp-bound form that features a three-helix bundle containing a canonical helix-turn-helix motif. However, this structure differs from all other LacR family members whose structures are known with regard to the packing of the helices and consequently their relative orientations. Aspects of CytR activity are unique among repressors; we identify here structural properties that are also distinct and that might underlie the different functional properties. © 2011 American Chemical Society

  10. Experience moderates overlap between object and face recognition, suggesting a common ability

    PubMed Central

    Gauthier, Isabel; McGugin, Rankin W.; Richler, Jennifer J.; Herzmann, Grit; Speegle, Magen; Van Gulick, Ana E.

    2014-01-01

    Some research finds that face recognition is largely independent from the recognition of other objects; a specialized and innate ability to recognize faces could therefore have little or nothing to do with our ability to recognize objects. We propose a new framework in which recognition performance for any category is the product of domain-general ability and category-specific experience. In Experiment 1, we show that the overlap between face and object recognition depends on experience with objects. In 256 subjects we measured face recognition, object recognition for eight categories, and self-reported experience with these categories. Experience predicted neither face recognition nor object recognition but moderated their relationship: Face recognition performance is increasingly similar to object recognition performance with increasing object experience. If a subject has a lot of experience with objects and is found to perform poorly, they also prove to have a low ability with faces. In a follow-up survey, we explored the dimensions of experience with objects that may have contributed to self-reported experience in Experiment 1. Different dimensions of experience appear to be more salient for different categories, with general self-reports of expertise reflecting judgments of verbal knowledge about a category more than judgments of visual performance. The complexity of experience and current limitations in its measurement support the importance of aggregating across multiple categories. Our findings imply that both face and object recognition are supported by a common, domain-general ability expressed through experience with a category and best measured when accounting for experience. PMID:24993021

  11. Experience moderates overlap between object and face recognition, suggesting a common ability.

    PubMed

    Gauthier, Isabel; McGugin, Rankin W; Richler, Jennifer J; Herzmann, Grit; Speegle, Magen; Van Gulick, Ana E

    2014-07-03

    Some research finds that face recognition is largely independent from the recognition of other objects; a specialized and innate ability to recognize faces could therefore have little or nothing to do with our ability to recognize objects. We propose a new framework in which recognition performance for any category is the product of domain-general ability and category-specific experience. In Experiment 1, we show that the overlap between face and object recognition depends on experience with objects. In 256 subjects we measured face recognition, object recognition for eight categories, and self-reported experience with these categories. Experience predicted neither face recognition nor object recognition but moderated their relationship: Face recognition performance is increasingly similar to object recognition performance with increasing object experience. If a subject has a lot of experience with objects and is found to perform poorly, they also prove to have a low ability with faces. In a follow-up survey, we explored the dimensions of experience with objects that may have contributed to self-reported experience in Experiment 1. Different dimensions of experience appear to be more salient for different categories, with general self-reports of expertise reflecting judgments of verbal knowledge about a category more than judgments of visual performance. The complexity of experience and current limitations in its measurement support the importance of aggregating across multiple categories. Our findings imply that both face and object recognition are supported by a common, domain-general ability expressed through experience with a category and best measured when accounting for experience. © 2014 ARVO.

  12. Oxytocin increases bias, but not accuracy, in face recognition line-ups.

    PubMed

    Bate, Sarah; Bennetts, Rachel; Parris, Benjamin A; Bindemann, Markus; Udale, Robert; Bussunt, Amanda

    2015-07-01

    Previous work indicates that intranasal inhalation of oxytocin improves face recognition skills, raising the possibility that it may be used in security settings. However, it is unclear whether oxytocin directly acts upon the core face-processing system itself or indirectly improves face recognition via affective or social salience mechanisms. In a double-blind procedure, 60 participants received either an oxytocin or placebo nasal spray before completing the One-in-Ten task-a standardized test of unfamiliar face recognition containing target-present and target-absent line-ups. Participants in the oxytocin condition outperformed those in the placebo condition on target-present trials, yet were more likely to make false-positive errors on target-absent trials. Signal detection analyses indicated that oxytocin induced a more liberal response bias, rather than increasing accuracy per se. These findings support a social salience account of the effects of oxytocin on face recognition and indicate that oxytocin may impede face recognition in certain scenarios. © The Author (2014). Published by Oxford University Press. For Permissions, please email: journals.permissions@oup.com.

  13. The rapamycin-binding domain of the protein kinase mammalian target of rapamycin is a destabilizing domain.

    PubMed

    Edwards, Sarah R; Wandless, Thomas J

    2007-05-04

    Rapamycin is an immunosuppressive drug that binds simultaneously to the 12-kDa FK506- and rapamycin-binding protein (FKBP12, or FKBP) and the FKBP-rapamycin binding (FRB) domain of the mammalian target of rapamycin (mTOR) kinase. The resulting ternary complex has been used to conditionally perturb protein function, and one such method involves perturbation of a protein of interest through its mislocalization. We synthesized two rapamycin derivatives that possess large substituents at the C-16 position within the FRB-binding interface, and these derivatives were screened against a library of FRB mutants using a three-hybrid assay in Saccharomyces cerevisiae. Several FRB mutants responded to one of the rapamycin derivatives, and twenty of these mutants were further characterized in mammalian cells. The mutants most responsive to the ligand were fused to yellow fluorescent protein, and fluorescence levels in the presence and absence of the ligand were measured to determine stability of the fusion proteins. Wild-type and mutant FRB domains were expressed at low levels in the absence of the rapamycin derivative, and expression levels rose up to 10-fold upon treatment with ligand. The synthetic rapamycin derivatives were further analyzed using quantitative mass spectrometry, and one of the compounds was found to contain contaminating rapamycin. Furthermore, uncontaminated analogs retained the ability to inhibit mTOR, although with diminished potency relative to rapamycin. The ligand-dependent stability displayed by wild-type FRB and FRB mutants as well as the inhibitory potential and purity of the rapamycin derivatives should be considered as potentially confounding experimental variables when using these systems.

  14. Structures of BIR domains from human NAIP and cIAP2

    PubMed Central

    Herman, Maria Dolores; Moche, Martin; Flodin, Susanne; Welin, Martin; Trésaugues, Lionel; Johansson, Ida; Nilsson, Martina; Nordlund, Pär; Nyman, Tomas

    2009-01-01

    The inhibitor of apoptosis (IAP) family of proteins contains key modulators of apoptosis and inflammation that interact with caspases through baculovirus IAP-repeat (BIR) domains. Overexpression of IAP proteins frequently occurs in cancer cells, thus counteracting the activated apoptotic program. The IAP proteins have therefore emerged as promising targets for cancer therapy. In this work, X-ray crystallography was used to determine the first structures of BIR domains from human NAIP and cIAP2. Both structures harbour an N-terminal tetrapeptide in the conserved peptide-binding groove. The structures reveal that these two proteins bind the tetrapeptides in a similar mode as do other BIR domains. Detailed interactions are described for the P1′–P4′ side chains of the peptide, providing a structural basis for peptide-specific recognition. An arginine side chain in the P3′ position reveals favourable interactions with its hydrophobic moiety in the binding pocket, while hydrophobic residues in the P2′ and P4′ pockets make similar interactions to those seen in other BIR domain–peptide complexes. The structures also reveal how a serine in the P1′ position is accommodated in the binding pockets of NAIP and cIAP2. In addition to shedding light on the specificity determinants of these two proteins, the structures should now also provide a framework for future structure-based work targeting these proteins. PMID:19923725

  15. Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma

    PubMed Central

    Li, Nan; Fu, Haiying; Hewitt, Stephen M.; Dimitrov, Dimiter S.

    2017-01-01

    Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma. PMID:28739923

  16. Therapeutically targeting glypican-2 via single-domain antibody-based chimeric antigen receptors and immunotoxins in neuroblastoma.

    PubMed

    Li, Nan; Fu, Haiying; Hewitt, Stephen M; Dimitrov, Dimiter S; Ho, Mitchell

    2017-08-08

    Neuroblastoma is a childhood cancer that is fatal in almost half of patients despite intense multimodality treatment. This cancer is derived from neuroendocrine tissue located in the sympathetic nervous system. Glypican-2 (GPC2) is a cell surface heparan sulfate proteoglycan that is important for neuronal cell adhesion and neurite outgrowth. In this study, we find that GPC2 protein is highly expressed in about half of neuroblastoma cases and that high GPC2 expression correlates with poor overall survival compared with patients with low GPC2 expression. We demonstrate that silencing of GPC2 by CRISPR-Cas9 or siRNA results in the inhibition of neuroblastoma tumor cell growth. GPC2 silencing inactivates Wnt/β-catenin signaling and reduces the expression of the target gene N-Myc, an oncogenic driver of neuroblastoma tumorigenesis. We have isolated human single-domain antibodies specific for GPC2 by phage display technology and found that the single-domain antibodies can inhibit active β-catenin signaling by disrupting the interaction of GPC2 and Wnt3a. To explore GPC2 as a potential target in neuroblastoma, we have developed two forms of antibody therapeutics, immunotoxins and chimeric antigen receptor (CAR) T cells. Immunotoxin treatment was demonstrated to inhibit neuroblastoma growth in mice. CAR T cells targeting GPC2 eliminated tumors in a disseminated neuroblastoma mouse model where tumor metastasis had spread to multiple clinically relevant sites, including spine, skull, legs, and pelvis. This study suggests GPC2 as a promising therapeutic target in neuroblastoma.

  17. Biophysical studies on calcium and carbohydrate binding to carbohydrate recognition domain of Gal/GalNAc lectin from Entamoeba histolytica: insights into host cell adhesion.

    PubMed

    Yadav, Rupali; Verma, Kuldeep; Chandra, Mintu; Mukherjee, Madhumita; Datta, Sunando

    2016-09-01

    Entamoeba histolytica, an enteric parasite expresses a Gal/GalNAc-specific lectin that contributes to its virulence by establishing adhesion to host cell. In this study, carbohydrate recognition domain of Hgl (EhCRD) was purified and biophysical studies were conducted to understand the thermodynamic basis of its binding to carbohydrate and Ca(++) Here, we show that carbohydrate recognition domain (CRD) of the lectin binds to calcium through DPN motif. To decipher the role of calcium in carbohydrate binding and host cell adhesion, biophysical and cell-based studies were carried out. We demonstrated that the presence of the cation neither change the affinity of the lectin for carbohydrates nor alters its conformation. Mutation of the calcium-binding motif in EhCRD resulted in complete loss of ability to bind calcium but retained its affinity for carbohydrates. Purified EhCRD significantly diminished adhesion of the amebic trophozoites to Chinese Hamster Ovary (CHO) cells as well as triggered red blood cell agglutination. The calcium-binding defective mutant abrogated amebic adhesion to CHO cells similar to the wild-type protein, but it failed to agglutinate RBCs suggesting a differential role of the cation in these two processes. This study provides the first molecular description of the role of calcium in Gal/GalNAc mediated host cell adhesion. © The Authors 2016. Published by Oxford University Press on behalf of the Japanese Biochemical Society. All rights reserved.

  18. Infrared maritime target detection using the high order statistic filtering in fractional Fourier domain

    NASA Astrophysics Data System (ADS)

    Zhou, Anran; Xie, Weixin; Pei, Jihong

    2018-06-01

    Accurate detection of maritime targets in infrared imagery under various sea clutter conditions is always a challenging task. The fractional Fourier transform (FRFT) is the extension of the Fourier transform in the fractional order, and has richer spatial-frequency information. By combining it with the high order statistic filtering, a new ship detection method is proposed. First, the proper range of angle parameter is determined to make it easier for the ship components and background to be separated. Second, a new high order statistic curve (HOSC) at each fractional frequency point is designed. It is proved that maximal peak interval in HOSC reflects the target information, while the points outside the interval reflect the background. And the value of HOSC relative to the ship is much bigger than that to the sea clutter. Then, search the curve's maximal target peak interval and extract the interval by bandpass filtering in fractional Fourier domain. The value outside the peak interval of HOSC decreases rapidly to 0, so the background is effectively suppressed. Finally, the detection result is obtained by the double threshold segmenting and the target region selection method. The results show the proposed method is excellent for maritime targets detection with high clutters.

  19. Frizzled 7 and PIP2 binding by syntenin PDZ2 domain supports Frizzled 7 trafficking and signalling

    NASA Astrophysics Data System (ADS)

    Egea-Jimenez, Antonio Luis; Gallardo, Rodrigo; Garcia-Pino, Abel; Ivarsson, Ylva; Wawrzyniak, Anna Maria; Kashyap, Rudra; Loris, Remy; Schymkowitz, Joost; Rousseau, Frederic; Zimmermann, Pascale

    2016-07-01

    PDZ domain-containing proteins work as intracellular scaffolds to control spatio-temporal aspects of cell signalling. This function is supported by the ability of their PDZ domains to bind other proteins such as receptors, but also phosphoinositide lipids important for membrane trafficking. Here we report a crystal structure of the syntenin PDZ tandem in complex with the carboxy-terminal fragment of Frizzled 7 and phosphatidylinositol 4,5-bisphosphate (PIP2). The crystal structure reveals a tripartite interaction formed via the second PDZ domain of syntenin. Biophysical and biochemical experiments establish co-operative binding of the tripartite complex and identify residues crucial for membrane PIP2-specific recognition. Experiments with cells support the importance of the syntenin-PIP2 interaction for plasma membrane targeting of Frizzled 7 and c-jun phosphorylation. This study contributes to our understanding of the biology of PDZ proteins as key players in membrane compartmentalization and dynamics.

  20. Modeling guidance and recognition in categorical search: bridging human and computer object detection.

    PubMed

    Zelinsky, Gregory J; Peng, Yifan; Berg, Alexander C; Samaras, Dimitris

    2013-10-08

    Search is commonly described as a repeating cycle of guidance to target-like objects, followed by the recognition of these objects as targets or distractors. Are these indeed separate processes using different visual features? We addressed this question by comparing observer behavior to that of support vector machine (SVM) models trained on guidance and recognition tasks. Observers searched for a categorically defined teddy bear target in four-object arrays. Target-absent trials consisted of random category distractors rated in their visual similarity to teddy bears. Guidance, quantified as first-fixated objects during search, was strongest for targets, followed by target-similar, medium-similarity, and target-dissimilar distractors. False positive errors to first-fixated distractors also decreased with increasing dissimilarity to the target category. To model guidance, nine teddy bear detectors, using features ranging in biological plausibility, were trained on unblurred bears then tested on blurred versions of the same objects appearing in each search display. Guidance estimates were based on target probabilities obtained from these detectors. To model recognition, nine bear/nonbear classifiers, trained and tested on unblurred objects, were used to classify the object that would be fixated first (based on the detector estimates) as a teddy bear or a distractor. Patterns of categorical guidance and recognition accuracy were modeled almost perfectly by an HMAX model in combination with a color histogram feature. We conclude that guidance and recognition in the context of search are not separate processes mediated by different features, and that what the literature knows as guidance is really recognition performed on blurred objects viewed in the visual periphery.

  1. Deciphering kinase-substrate relationships by analysis of domain-specific phosphorylation network.

    PubMed

    Damle, Nikhil Prakash; Mohanty, Debasisa

    2014-06-15

    In silico prediction of site-specific kinase-substrate relationships (ssKSRs) is crucial for deciphering phosphorylation networks by linking kinomes to phosphoproteomes. However, currently available predictors for ssKSRs give rise to a large number of false-positive results because they use only a short sequence stretch around phosphosite as determinants of kinase specificity and do not consider the biological context of kinase-substrate recognition. Based on the analysis of domain-specific kinase-substrate relationships, we have constructed a domain-level phosphorylation network that implicitly incorporates various contextual factors. It reveals preferential phosphorylation of specific domains by certain kinases. These novel correlations have been implemented in PhosNetConstruct, an automated program for predicting target kinases for a substrate protein. PhosNetConstruct distinguishes cognate kinase-substrate pairs from a large number of non-cognate combinations. Benchmarking on independent datasets using various statistical measures demonstrates the superior performance of PhosNetConstruct over ssKSR-based predictors. PhosNetConstruct is freely available at http://www.nii.ac.in/phosnetconstruct.html. © The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  2. Directed evolution of FLS2 towards novel flagellin peptide recognition

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

    Helft, Laura; Thompson, Mikayla; Bent, Andrew F.

    Microbe-associated molecular patterns (MAMPs) are molecules, or domains within molecules, that are conserved across microbial taxa and can be recognized by a plant or animal immune system. Although MAMP receptors have evolved to recognize conserved epitopes, the MAMPs in some microbial species or strains have diverged sufficiently to render them unrecognizable by some host immune systems. In this study, we carried out in vitro evolution of the Arabidopsis thaliana flagellin receptor FLAGELLIN-SENSING 2 (FLS2) to isolate derivatives that recognize one or more flagellin peptides from bacteria for which the wildtype Arabidopsis FLS2 confers little or no response. A targeted approachmore » generated amino acid variation at FLS2 residues in a region previously implicated in flagellin recognition. The primary screen tested for elevated response to the canonical flagellin peptide from Pseudomonas aeruginosa, flg22. From this pool, we then identified five alleles of FLS2 that confer modest (quantitatively partial) recognition of an Erwinia amylovora flagellin peptide. Use of this Erwinia-based flagellin peptide to stimulate Arabidopsis plants expressing the resulting FLS2 alleles did not lead to a detectable reduction of virulent P. syringae pv. tomato growth. However, combination of two identified mutations into a single allele further increased FLS2-mediated responses to the E. amylovora flagellin peptide. Furthermore, these studies demonstrate the potential to raise the sensitivity of MAMP receptors toward particular targets.« less

  3. Directed evolution of FLS2 towards novel flagellin peptide recognition

    DOE PAGES

    Helft, Laura; Thompson, Mikayla; Bent, Andrew F.

    2016-06-06

    Microbe-associated molecular patterns (MAMPs) are molecules, or domains within molecules, that are conserved across microbial taxa and can be recognized by a plant or animal immune system. Although MAMP receptors have evolved to recognize conserved epitopes, the MAMPs in some microbial species or strains have diverged sufficiently to render them unrecognizable by some host immune systems. In this study, we carried out in vitro evolution of the Arabidopsis thaliana flagellin receptor FLAGELLIN-SENSING 2 (FLS2) to isolate derivatives that recognize one or more flagellin peptides from bacteria for which the wildtype Arabidopsis FLS2 confers little or no response. A targeted approachmore » generated amino acid variation at FLS2 residues in a region previously implicated in flagellin recognition. The primary screen tested for elevated response to the canonical flagellin peptide from Pseudomonas aeruginosa, flg22. From this pool, we then identified five alleles of FLS2 that confer modest (quantitatively partial) recognition of an Erwinia amylovora flagellin peptide. Use of this Erwinia-based flagellin peptide to stimulate Arabidopsis plants expressing the resulting FLS2 alleles did not lead to a detectable reduction of virulent P. syringae pv. tomato growth. However, combination of two identified mutations into a single allele further increased FLS2-mediated responses to the E. amylovora flagellin peptide. Furthermore, these studies demonstrate the potential to raise the sensitivity of MAMP receptors toward particular targets.« less

  4. Calcium binding to calmodulin mutants monitored by domain-specific intrinsic phenylalanine and tyrosine fluorescence.

    PubMed Central

    VanScyoc, Wendy S; Sorensen, Brenda R; Rusinova, Elena; Laws, William R; Ross, J B Alexander; Shea, Madeline A

    2002-01-01

    of sites in both domains. This approach holds promise for exploring the linked energetics of calcium binding and target recognition. PMID:12414709

  5. Chloroplastic protein NRIP1 mediates innate immune receptor recognition of a viral effector

    PubMed Central

    Caplan, Jeffrey L.; Mamillapalli, Padmavathi; Burch-Smith, Tessa M.; Czymmek, Kirk; Dinesh-Kumar, S.P.

    2008-01-01

    Summary Plant innate immunity relies on the recognition of pathogen effector molecules by nucleotide-binding-leucine-rich repeat (NB-LRR) immune receptor families. Previously we have shown the N immune receptor, a member of TIR-NB-LRR family, indirectly recognizes the 50-kDa helicase (p50) domain of Tobacco mosaic virus (TMV) through its TIR domain. We have identified an N receptor-interacting protein, NRIP1, that directly interacts with both N's TIR domain and p50. NRIP1 is a functional rhodanese sulfurtransferase and is required for N to provide complete resistance to TMV. Interestingly, NRIP1 that normally localizes to the chloroplasts is recruited to the cytoplasm and nucleus by the p50 effector. As a consequence, NRIP1 interacts with N only in the presence of the p50 effector. Our findings show that a chloroplastic protein is intimately involved in pathogen recognition. We propose that N's activation requires a pre-recognition complex containing the p50 effector and NRIP1. PMID:18267075

  6. Interaction of the Transactivation Domain of B-Myb with the TAZ2 Domain of the Coactivator p300: Molecular Features and Properties of the Complex

    PubMed Central

    Oka, Ojore; Waters, Lorna C.; Strong, Sarah L.; Dosanjh, Nuvjeevan S.; Veverka, Vaclav; Muskett, Frederick W.; Renshaw, Philip S.; Klempnauer, Karl-Heinz; Carr, Mark D.

    2012-01-01

    The transcription factor B-Myb is a key regulator of the cell cycle in vertebrates, with activation of transcription involving the recognition of specific DNA target sites and the recruitment of functional partner proteins, including the coactivators p300 and CBP. Here we report the results of detailed studies of the interaction between the transactivation domain of B-Myb (B-Myb TAD) and the TAZ2 domain of p300. The B-Myb TAD was characterized using circular dichroism, fluorescence and NMR spectroscopy, which revealed that the isolated domain exists as a random coil polypeptide. Pull-down and spectroscopic experiments clearly showed that the B-Myb TAD binds to p300 TAZ2 to form a moderately tight (Kd ∼1.0–10 µM) complex, which results in at least partial folding of the B-Myb TAD. Significant changes in NMR spectra of p300 TAZ2 suggest that the B-Myb TAD binds to a relatively large patch on the surface of the domain (∼1200 Å2). The apparent B-Myb TAD binding site on p300 TAZ2 shows striking similarity to the surface of CBP TAZ2 involved in binding to the transactivation domain of the transcription factor signal transducer and activator of transcription 1 (STAT1), which suggests that the structure of the B-Myb TAD-p300 TAZ2 complex may share many features with that reported for STAT1 TAD-p300 TAZ2. PMID:23300815

  7. Assessment of Homomorphic Analysis for Human Activity Recognition from Acceleration Signals.

    PubMed

    Vanrell, Sebastian Rodrigo; Milone, Diego Humberto; Rufiner, Hugo Leonardo

    2017-07-03

    Unobtrusive activity monitoring can provide valuable information for medical and sports applications. In recent years, human activity recognition has moved to wearable sensors to deal with unconstrained scenarios. Accelerometers are the preferred sensors due to their simplicity and availability. Previous studies have examined several \\azul{classic} techniques for extracting features from acceleration signals, including time-domain, time-frequency, frequency-domain, and other heuristic features. Spectral and temporal features are the preferred ones and they are generally computed from acceleration components, leaving the acceleration magnitude potential unexplored. In this study, based on homomorphic analysis, a new type of feature extraction stage is proposed in order to exploit discriminative activity information present in acceleration signals. Homomorphic analysis can isolate the information about whole body dynamics and translate it into a compact representation, called cepstral coefficients. Experiments have explored several configurations of the proposed features, including size of representation, signals to be used, and fusion with other features. Cepstral features computed from acceleration magnitude obtained one of the highest recognition rates. In addition, a beneficial contribution was found when time-domain and moving pace information was included in the feature vector. Overall, the proposed system achieved a recognition rate of 91.21% on the publicly available SCUT-NAA dataset. To the best of our knowledge, this is the highest recognition rate on this dataset.

  8. Ligand-Binding Properties and Conformational Dynamics of Autolysin Repeat Domains in Staphylococcal Cell Wall Recognition

    PubMed Central

    Zoll, Sebastian; Schlag, Martin; Shkumatov, Alexander V.; Rautenberg, Maren; Svergun, Dmitri I.; Götz, Friedrich

    2012-01-01

    The bifunctional major autolysin Atl plays a key role in staphylococcal cell separation. Processing of Atl yields catalytically active amidase (AM) and glucosaminidase (GL) domains that are each fused to repeating units. The two repeats of AM (R1 and R2) target the enzyme to the septum, where it cleaves murein between dividing cells. We have determined the crystal structure of R2, which reveals that each repeat folds into two half-open β-barrel subunits. We further demonstrate that lipoteichoic acid serves as a receptor for the repeats and that this interaction depends on conserved surfaces in each subunit. Small-angle X-ray scattering of the mature amidase reveals the presence of flexible linkers separating the AM, R1, and R2 units. Different levels of flexibility for each linker provide mechanistic insights into the conformational dynamics of the full-length protein and the roles of its components in cell wall association and catalysis. Our analysis supports a model in which the repeats direct the catalytic AM domain to the septum, where it can optimally perform the final step of cell division. PMID:22609916

  9. The Invariance Hypothesis Implies Domain-Specific Regions in Visual Cortex

    PubMed Central

    Leibo, Joel Z.; Liao, Qianli; Anselmi, Fabio; Poggio, Tomaso

    2015-01-01

    Is visual cortex made up of general-purpose information processing machinery, or does it consist of a collection of specialized modules? If prior knowledge, acquired from learning a set of objects is only transferable to new objects that share properties with the old, then the recognition system’s optimal organization must be one containing specialized modules for different object classes. Our analysis starts from a premise we call the invariance hypothesis: that the computational goal of the ventral stream is to compute an invariant-to-transformations and discriminative signature for recognition. The key condition enabling approximate transfer of invariance without sacrificing discriminability turns out to be that the learned and novel objects transform similarly. This implies that the optimal recognition system must contain subsystems trained only with data from similarly-transforming objects and suggests a novel interpretation of domain-specific regions like the fusiform face area (FFA). Furthermore, we can define an index of transformation-compatibility, computable from videos, that can be combined with information about the statistics of natural vision to yield predictions for which object categories ought to have domain-specific regions in agreement with the available data. The result is a unifying account linking the large literature on view-based recognition with the wealth of experimental evidence concerning domain-specific regions. PMID:26496457

  10. Is it me? Self-recognition bias across sensory modalities and its relationship to autistic traits.

    PubMed

    Chakraborty, Anya; Chakrabarti, Bhismadev

    2015-01-01

    Atypical self-processing is an emerging theme in autism research, suggested by lower self-reference effect in memory, and atypical neural responses to visual self-representations. Most research on physical self-processing in autism uses visual stimuli. However, the self is a multimodal construct, and therefore, it is essential to test self-recognition in other sensory modalities as well. Self-recognition in the auditory modality remains relatively unexplored and has not been tested in relation to autism and related traits. This study investigates self-recognition in auditory and visual domain in the general population and tests if it is associated with autistic traits. Thirty-nine neurotypical adults participated in a two-part study. In the first session, individual participant's voice was recorded and face was photographed and morphed respectively with voices and faces from unfamiliar identities. In the second session, participants performed a 'self-identification' task, classifying each morph as 'self' voice (or face) or an 'other' voice (or face). All participants also completed the Autism Spectrum Quotient (AQ). For each sensory modality, slope of the self-recognition curve was used as individual self-recognition metric. These two self-recognition metrics were tested for association between each other, and with autistic traits. Fifty percent 'self' response was reached for a higher percentage of self in the auditory domain compared to the visual domain (t = 3.142; P < 0.01). No significant correlation was noted between self-recognition bias across sensory modalities (τ = -0.165, P = 0.204). Higher recognition bias for self-voice was observed in individuals higher in autistic traits (τ AQ = 0.301, P = 0.008). No such correlation was observed between recognition bias for self-face and autistic traits (τ AQ = -0.020, P = 0.438). Our data shows that recognition bias for physical self-representation is not related across sensory modalities. Further

  11. The Relationships among Facial Emotion Recognition, Social Skills, and Quality of Life.

    ERIC Educational Resources Information Center

    Simon, Elliott W.; And Others

    1995-01-01

    Forty-six institutionalized adults with mild or moderate mental retardation were administered the Vineland Adaptive Behavior Scales (socialization domain), a subjective measure of quality of life, and a facial emotion recognition test. Facial emotion recognition, quality of life, and social skills appeared to be independent of one another. Facial…

  12. Prostate Cancer Cells Express More Androgen Receptor (AR) Following Androgen Deprivation, Improving Recognition by AR-Specific T Cells.

    PubMed

    Olson, Brian M; Gamat, Melissa; Seliski, Joseph; Sawicki, Thomas; Jeffery, Justin; Ellis, Leigh; Drake, Charles G; Weichert, Jamey; McNeel, Douglas G

    2017-12-01

    Androgen deprivation is the primary therapy for recurrent prostate cancer, and agents targeting the androgen receptor (AR) pathway continue to be developed. Because androgen-deprivation therapy (ADT) has immmunostimulatory effects as well as direct antitumor effects, AR-targeted therapies have been combined with other anticancer therapies, including immunotherapies. Here, we sought to study whether an antigen-specific mechanism of resistance to ADT (overexpression of the AR) may result in enhanced AR-specific T-cell immune recognition, and whether this might be strategically combined with an antitumor vaccine targeting the AR. Androgen deprivation increased AR expression in human and murine prostate tumor cells in vitro and in vivo The increased expression persisted over time. Increased AR expression was associated with recognition and cytolytic activity by AR-specific T cells. Furthermore, ADT combined with vaccination, specifically a DNA vaccine encoding the ligand-binding domain of the AR, led to improved antitumor responses as measured by tumor volumes and delays in the emergence of castrate-resistant prostate tumors in two murine prostate cancer models (Myc-CaP and prostate-specific PTEN-deficient mice). Together, these data suggest that ADT combined with AR-directed immunotherapy targets a major mechanism of resistance, overexpression of the AR. This combination may be more effective than ADT combined with other immunotherapeutic approaches. Cancer Immunol Res; 5(12); 1074-85. ©2017 AACR . ©2017 American Association for Cancer Research.

  13. Using peptide array to identify binding motifs and interaction networks for modular domains.

    PubMed

    Li, Shawn S-C; Wu, Chenggang

    2009-01-01

    Specific protein-protein interactions underlie all essential biological processes and form the basis of cellular signal transduction. The recognition of a short, linear peptide sequence in one protein by a modular domain in another represents a common theme of macromolecular recognition in cells, and the importance of this mode of protein-protein interaction is highlighted by the large number of peptide-binding domains encoded by the human genome. This phenomenon also provides a unique opportunity to identify protein-protein binding events using peptide arrays and complementary biochemical assays. Accordingly, high-density peptide array has emerged as a useful tool by which to map domain-mediated protein-protein interaction networks at the proteome level. Using the Src-homology 2 (SH2) and 3 (SH3) domains as examples, we describe the application of oriented peptide array libraries in uncovering specific motifs recognized by an SH2 domain and the use of high-density peptide arrays in identifying interaction networks mediated by the SH3 domain. Methods reviewed here could also be applied to other modular domains, including catalytic domains, that recognize linear peptide sequences.

  14. Adaptive Immunity against Leishmania Nucleoside Hydrolase Maps Its C-Terminal Domain as the Target of the CD4+ T Cell–Driven Protective Response

    PubMed Central

    Nico, Dirlei; Claser, Carla; Borja-Cabrera, Gulnara P.; Travassos, Luiz R.; Palatnik, Marcos; da Silva Soares, Irene; Rodrigues, Mauricio Martins; Palatnik-de-Sousa, Clarisa B.

    2010-01-01

    Nucleoside hydrolases (NHs) show homology among parasite protozoa, fungi and bacteria. They are vital protagonists in the establishment of early infection and, therefore, are excellent candidates for the pathogen recognition by adaptive immune responses. Immune protection against NHs would prevent disease at the early infection of several pathogens. We have identified the domain of the NH of L. donovani (NH36) responsible for its immunogenicity and protective efficacy against murine visceral leishmaniasis (VL). Using recombinant generated peptides covering the whole NH36 sequence and saponin we demonstrate that protection against L. chagasi is related to its C-terminal domain (amino-acids 199–314) and is mediated mainly by a CD4+ T cell driven response with a lower contribution of CD8+ T cells. Immunization with this peptide exceeds in 36.73±12.33% the protective response induced by the cognate NH36 protein. Increases in IgM, IgG2a, IgG1 and IgG2b antibodies, CD4+ T cell proportions, IFN-γ secretion, ratios of IFN-γ/IL-10 producing CD4+ and CD8+ T cells and percents of antibody binding inhibition by synthetic predicted epitopes were detected in F3 vaccinated mice. The increases in DTH and in ratios of TNFα/IL-10 CD4+ producing cells were however the strong correlates of protection which was confirmed by in vivo depletion with monoclonal antibodies, algorithm predicted CD4 and CD8 epitopes and a pronounced decrease in parasite load (90.5–88.23%; p = 0.011) that was long-lasting. No decrease in parasite load was detected after vaccination with the N-domain of NH36, in spite of the induction of IFN-γ/IL-10 expression by CD4+ T cells after challenge. Both peptides reduced the size of footpad lesions, but only the C-domain reduced the parasite load of mice challenged with L. amazonensis. The identification of the target of the immune response to NH36 represents a basis for the rationale development of a bivalent vaccine against leishmaniasis and for

  15. A bio-recognition device developed onto nano-crystals of carbonate apatite for cell-targeted gene delivery.

    PubMed

    Chowdhury, E H; Akaike, Toshihiro

    2005-05-20

    The DNA delivery to mammalian cells is an essential tool for analyzing gene structure, regulation, and function. The approach holds great promise for the further development of gene therapy techniques and DNA vaccination strategies to treat and control diseases. Here, we report on the establishment of a cell-specific gene delivery and expression system by physical adsorption of a cell-recognition molecule on the nano-crystal surface of carbonate apatite. As a model, DNA/nano-particles were successfully coated with asialofetuin to facilitate uptake by hepatocyte-derived cell lines through the asialoglycoprotein receptor (ASGPr) and albumin to prevent non-specific interactions of the particles with cell-surface. The resulting composite particles with dual surface properties could accelerate DNA uptake and enhance expression to a notable extent. Nano-particles coated with transferrin in the same manner dramatically enhanced transgene expression in the corresponding receptor-bearing cells and thus our newly developed strategy represents a universal phenomenon for anchoring a bio-recognition macromolecule on the apatite crystal surface for targeted gene delivery, having immediate applications in basic research laboratories and great promise for gene therapy. (c) 2005 Wiley Periodicals, Inc.

  16. It Takes Two–Skilled Recognition of Objects Engages Lateral Areas in Both Hemispheres

    PubMed Central

    Bilalić, Merim; Kiesel, Andrea; Pohl, Carsten; Erb, Michael; Grodd, Wolfgang

    2011-01-01

    Our object recognition abilities, a direct product of our experience with objects, are fine-tuned to perfection. Left temporal and lateral areas along the dorsal, action related stream, as well as left infero-temporal areas along the ventral, object related stream are engaged in object recognition. Here we show that expertise modulates the activity of dorsal areas in the recognition of man-made objects with clearly specified functions. Expert chess players were faster than chess novices in identifying chess objects and their functional relations. Experts' advantage was domain-specific as there were no differences between groups in a control task featuring geometrical shapes. The pattern of eye movements supported the notion that experts' extensive knowledge about domain objects and their functions enabled superior recognition even when experts were not directly fixating the objects of interest. Functional magnetic resonance imaging (fMRI) related exclusively the areas along the dorsal stream to chess specific object recognition. Besides the commonly involved left temporal and parietal lateral brain areas, we found that only in experts homologous areas on the right hemisphere were also engaged in chess specific object recognition. Based on these results, we discuss whether skilled object recognition does not only involve a more efficient version of the processes found in non-skilled recognition, but also qualitatively different cognitive processes which engage additional brain areas. PMID:21283683

  17. Structural basis for microRNA targeting

    DOE PAGES

    Schirle, Nicole T.; Sheu-Gruttadauria, Jessica; MacRae, Ian J.

    2014-10-31

    MicroRNAs (miRNAs) control expression of thousands of genes in plants and animals. miRNAs function by guiding Argonaute proteins to complementary sites in messenger RNAs (mRNAs) targeted for repression. In this paper, we determined crystal structures of human Argonaute-2 (Ago2) bound to a defined guide RNA with and without target RNAs representing miRNA recognition sites. These structures suggest a stepwise mechanism, in which Ago2 primarily exposes guide nucleotides (nt) 2 to 5 for initial target pairing. Pairing to nt 2 to 5 promotes conformational changes that expose nt 2 to 8 and 13 to 16 for further target recognition. Interactions withmore » the guide-target minor groove allow Ago2 to interrogate target RNAs in a sequence-independent manner, whereas an adenosine binding-pocket opposite guide nt 1 further facilitates target recognition. Spurious slicing of miRNA targets is avoided through an inhibitory coordination of one catalytic magnesium ion. Finally, these results explain the conserved nucleotide-pairing patterns in animal miRNA target sites first observed over two decades ago.« less

  18. Modeling guidance and recognition in categorical search: Bridging human and computer object detection

    PubMed Central

    Zelinsky, Gregory J.; Peng, Yifan; Berg, Alexander C.; Samaras, Dimitris

    2013-01-01

    Search is commonly described as a repeating cycle of guidance to target-like objects, followed by the recognition of these objects as targets or distractors. Are these indeed separate processes using different visual features? We addressed this question by comparing observer behavior to that of support vector machine (SVM) models trained on guidance and recognition tasks. Observers searched for a categorically defined teddy bear target in four-object arrays. Target-absent trials consisted of random category distractors rated in their visual similarity to teddy bears. Guidance, quantified as first-fixated objects during search, was strongest for targets, followed by target-similar, medium-similarity, and target-dissimilar distractors. False positive errors to first-fixated distractors also decreased with increasing dissimilarity to the target category. To model guidance, nine teddy bear detectors, using features ranging in biological plausibility, were trained on unblurred bears then tested on blurred versions of the same objects appearing in each search display. Guidance estimates were based on target probabilities obtained from these detectors. To model recognition, nine bear/nonbear classifiers, trained and tested on unblurred objects, were used to classify the object that would be fixated first (based on the detector estimates) as a teddy bear or a distractor. Patterns of categorical guidance and recognition accuracy were modeled almost perfectly by an HMAX model in combination with a color histogram feature. We conclude that guidance and recognition in the context of search are not separate processes mediated by different features, and that what the literature knows as guidance is really recognition performed on blurred objects viewed in the visual periphery. PMID:24105460

  19. Close encounters of the third kind: disordered domains and the interactions of proteins.

    PubMed

    Tompa, Peter; Fuxreiter, Monika; Oldfield, Christopher J; Simon, Istvan; Dunker, A Keith; Uversky, Vladimir N

    2009-03-01

    Protein-protein interactions are thought to be mediated by domains, which are autonomous folding units of proteins. Recently, a second type of interaction has been suggested, mediated by short segments termed linear motifs, which are related to recognition elements of intrinsically disordered regions. Here, we propose a third kind of protein-protein recognition mechanism, mediated by disordered regions longer than 20-30 residues. Bioinformatics predictions and well-characterized examples, such as the kinase-inhibitory domain of Cdk inhibitors and the Wiskott-Aldrich syndrome protein (WASP)-homology domain 2 of actin-binding proteins, show that these disordered regions conform to the definition of domains rather than motifs, i.e., they represent functional, evolutionary, and structural units. Their functions are distinct from those of short motifs and ordered domains, and establish a third kind of interaction principle. With these points, we argue that these long disordered regions should be recognized as a distinct class of biologically functional protein domains.

  20. Structural basis for the recognition of Asef by adenomatous polyposis coli

    PubMed Central

    Zhang, Zhenyi; Chen, Leyi; Gao, Lei; Lin, Kui; Zhu, Liang; Lu, Yang; Shi, Xiaoshan; Gao, Yuan; Zhou, Jing; Xu, Ping; Zhang, Jian; Wu, Geng

    2012-01-01

    Adenomatous polyposis coli (APC) regulates cell-cell adhesion and cell migration through activating the APC-stimulated guanine nucleotide-exchange factor (GEF; Asef), which is usually autoinhibited through the binding between its Src homology 3 (SH3) and Dbl homology (DH) domains. The APC-activated Asef stimulates the small GTPase Cdc42, which leads to decreased cell-cell adherence and enhanced cell migration. In colorectal cancers, truncated APC constitutively activates Asef and promotes cancer cell migration and angiogenesis. Here, we report crystal structures of the human APC/Asef complex. We find that the armadillo repeat domain of APC uses a highly conserved surface groove to recognize the APC-binding region (ABR) of Asef, conformation of which changes dramatically upon binding to APC. Key residues on APC and Asef for the complex formation were mutated and their importance was demonstrated by binding and activity assays. Structural superimposition of the APC/Asef complex with autoinhibited Asef suggests that the binding between APC and Asef might create a steric clash between Asef-DH domain and APC, which possibly leads to a conformational change in Asef that stimulates its GEF activity. Our structures thus elucidate the molecular mechanism of Asef recognition by APC, as well as provide a potential target for pharmaceutical intervention against cancers. PMID:21788986

  1. N-terminal functional domain of Gasdermin A3 regulates mitochondrial homeostasis via mitochondrial targeting.

    PubMed

    Lin, Pei-Hsuan; Lin, Hsien-Yi; Kuo, Cheng-Chin; Yang, Liang-Tung

    2015-06-24

    The epidermis forms a critical barrier that is maintained by orchestrated programs of proliferation, differentiation, and cell death. Gene mutations that disturb this turnover process may cause skin diseases. Human GASDERMIN A (GSDMA) is frequently silenced in gastric cancer cell lines and its overexpression has been reported to induce apoptosis. GSDMA has also been linked with airway hyperresponsiveness in genetic association studies. The function of GSDMA in the skin was deduced by dominant mutations in mouse gasdermin A3 (Gsdma3), which caused skin inflammation and hair loss. However, the mechanism for the autosomal dominance of Gsdma3 mutations and the mode of Gsdma3's action remain unanswered. We demonstrated a novel function of Gsdma3 in modulating mitochondrial oxidative stress. We showed that Gsdma3 is regulated by intramolecular fold-back inhibition, which is disrupted by dominant mutations in the C-terminal domain. The unmasked N-terminal domain of Gsdma3 associates with Hsp90 and is delivered to mitochondrial via mitochondrial importer receptor Tom70, where it interacts with the mitochondrial chaperone Trap1 and causes increased production of mitochondrial reactive oxygen species (ROS), dissipation of mitochondrial membrane potential, and mitochondrial permeability transition (MPT). Overexpression of the C-terminal domain of Gsdma3 as well as pharmacological interventions of mitochondrial translocation, ROS production, and MPT pore opening alleviate the cell death induced by Gsdma3 mutants. Our results indicate that the genetic mutations in the C-terminal domain of Gsdma3 are gain-of-function mutations which unmask the N-terminal functional domain of Gsdma3. Gsdma3 regulates mitochondrial oxidative stress through mitochondrial targeting. Since mitochondrial ROS has been shown to promote epidermal differentiation, we hypothesize that Gsdma3 regulates context-dependent response of keratinocytes to differentiation and cell death signals by impinging on

  2. Domain-Invariant Partial-Least-Squares Regression.

    PubMed

    Nikzad-Langerodi, Ramin; Zellinger, Werner; Lughofer, Edwin; Saminger-Platz, Susanne

    2018-05-11

    Multivariate calibration models often fail to extrapolate beyond the calibration samples because of changes associated with the instrumental response, environmental condition, or sample matrix. Most of the current methods used to adapt a source calibration model to a target domain exclusively apply to calibration transfer between similar analytical devices, while generic methods for calibration-model adaptation are largely missing. To fill this gap, we here introduce domain-invariant partial-least-squares (di-PLS) regression, which extends ordinary PLS by a domain regularizer in order to align the source and target distributions in the latent-variable space. We show that a domain-invariant weight vector can be derived in closed form, which allows the integration of (partially) labeled data from the source and target domains as well as entirely unlabeled data from the latter. We test our approach on a simulated data set where the aim is to desensitize a source calibration model to an unknown interfering agent in the target domain (i.e., unsupervised model adaptation). In addition, we demonstrate unsupervised, semisupervised, and supervised model adaptation by di-PLS on two real-world near-infrared (NIR) spectroscopic data sets.

  3. Instructional Design for Advanced Learners: Training Recognition Skills to Hasten Expertise

    ERIC Educational Resources Information Center

    Fadde, Peter Jae

    2009-01-01

    Expertise in domains ranging from sports to surgery involves a process of recognition-primed decision-making (RPD) in which experts make rapid, intuitive decisions based on recognizing critical features of dynamic performance situations. While the development of expert RPD is assumed to require years of domain experience, the transition from…

  4. Do pattern recognition skills transfer across sports? A preliminary analysis.

    PubMed

    Smeeton, Nicholas J; Ward, Paul; Williams, A Mark

    2004-02-01

    The ability to recognize patterns of play is fundamental to performance in team sports. While typically assumed to be domain-specific, pattern recognition skills may transfer from one sport to another if similarities exist in the perceptual features and their relations and/or the strategies used to encode and retrieve relevant information. A transfer paradigm was employed to compare skilled and less skilled soccer, field hockey and volleyball players' pattern recognition skills. Participants viewed structured and unstructured action sequences from each sport, half of which were randomly represented with clips not previously seen. The task was to identify previously viewed action sequences quickly and accurately. Transfer of pattern recognition skill was dependent on the participant's skill, sport practised, nature of the task and degree of structure. The skilled soccer and hockey players were quicker than the skilled volleyball players at recognizing structured soccer and hockey action sequences. Performance differences were not observed on the structured volleyball trials between the skilled soccer, field hockey and volleyball players. The skilled field hockey and soccer players were able to transfer perceptual information or strategies between their respective sports. The less skilled participants' results were less clear. Implications for domain-specific expertise, transfer and diversity across domains are discussed.

  5. Solution structure of a DNA mimicking motif of an RNA aptamer against transcription factor AML1 Runt domain.

    PubMed

    Nomura, Yusuke; Tanaka, Yoichiro; Fukunaga, Jun-ichi; Fujiwara, Kazuya; Chiba, Manabu; Iibuchi, Hiroaki; Tanaka, Taku; Nakamura, Yoshikazu; Kawai, Gota; Kozu, Tomoko; Sakamoto, Taiichi

    2013-12-01

    AML1/RUNX1 is an essential transcription factor involved in the differentiation of hematopoietic cells. AML1 binds to the Runt-binding double-stranded DNA element (RDE) of target genes through its N-terminal Runt domain. In a previous study, we obtained RNA aptamers against the AML1 Runt domain by systematic evolution of ligands by exponential enrichment and revealed that RNA aptamers exhibit higher affinity for the Runt domain than that for RDE and possess the 5'-GCGMGNN-3' and 5'-N'N'CCAC-3' conserved motif (M: A or C; N and N' form Watson-Crick base pairs) that is important for Runt domain binding. In this study, to understand the structural basis of recognition of the Runt domain by the aptamer motif, the solution structure of a 22-mer RNA was determined using nuclear magnetic resonance. The motif contains the AH(+)-C mismatch and base triple and adopts an unusual backbone structure. Structural analysis of the aptamer motif indicated that the aptamer binds to the Runt domain by mimicking the RDE sequence and structure. Our data should enhance the understanding of the structural basis of DNA mimicry by RNA molecules.

  6. Recognition without Awareness: Encoding and Retrieval Factors

    ERIC Educational Resources Information Center

    Craik, Fergus I. M.; Rose, Nathan S.; Gopie, Nigel

    2015-01-01

    The article reports 4 experiments that explore the notion of recognition without awareness using words as the material. Previous work by Voss and associates has shown that complex visual patterns were correctly selected as targets in a 2-alternative forced-choice (2-AFC) recognition test although participants reported that they were guessing. The…

  7. A bi-functional antibody-receptor domain fusion protein simultaneously targeting IGF-IR and VEGF for degradation

    PubMed Central

    Shen, Yang; Zeng, Lin; Novosyadlyy, Ruslan; Forest, Amelie; Zhu, Aiping; Korytko, Andrew; Zhang, Haifan; Eastman, Scott W; Topper, Michael; Hindi, Sagit; Covino, Nicole; Persaud, Kris; Kang, Yun; Burtrum, Douglas; Surguladze, David; Prewett, Marie; Chintharlapalli, Sudhakar; Wroblewski, Victor J; Shen, Juqun; Balderes, Paul; Zhu, Zhenping; Snavely, Marshall; Ludwig, Dale L

    2015-01-01

    Bi-specific antibodies (BsAbs), which can simultaneously block 2 tumor targets, have emerged as promising therapeutic alternatives to combinations of individual monoclonal antibodies. Here, we describe the engineering and development of a novel, human bi-functional antibody-receptor domain fusion molecule with ligand capture (bi-AbCap) through the fusion of the domain 2 of human vascular endothelial growth factor receptor 1 (VEGFR1) to an antibody directed against insulin-like growth factor – type I receptor (IGF-IR). The bi-AbCap possesses excellent stability and developability, and is the result of minimal engineering. Beyond potent neutralizing activities against IGF-IR and VEGF, the bi-AbCap is capable of cross-linking VEGF to IGF-IR, leading to co-internalization and degradation of both targets by tumor cells. In multiple mouse xenograft tumor models, the bi-AbCap improves anti-tumor activity over individual monotherapies. More importantly, it exhibits superior inhibition of tumor growth, compared with the combination of anti-IGF-IR and anti-VEGF therapies, via powerful blockade of both direct tumor cell growth and tumor angiogenesis. The unique “capture-for-degradation” mechanism of the bi-AbCap is informative for the design of next-generation bi-functional anti-cancer therapies directed against independent signaling pathways. The bi-AbCap design represents an alternative approach to the creation of dual-targeting antibody fusion molecules by taking advantage of natural receptor-ligand interactions. PMID:26073904

  8. Fingerprint recognition system by use of graph matching

    NASA Astrophysics Data System (ADS)

    Shen, Wei; Shen, Jun; Zheng, Huicheng

    2001-09-01

    Fingerprint recognition is an important subject in biometrics to identify or verify persons by physiological characteristics, and has found wide applications in different domains. In the present paper, we present a finger recognition system that combines singular points and structures. The principal steps of processing in our system are: preprocessing and ridge segmentation, singular point extraction and selection, graph representation, and finger recognition by graphs matching. Our fingerprint recognition system is implemented and tested for many fingerprint images and the experimental result are satisfactory. Different techniques are used in our system, such as fast calculation of orientation field, local fuzzy dynamical thresholding, algebraic analysis of connections and fingerprints representation and matching by graphs. Wed find that for fingerprint database that is not very large, the recognition rate is very high even without using a prior coarse category classification. This system works well for both one-to-few and one-to-many problems.

  9. Atomic structure of the nuclear pore complex targeting domain of a Nup116 homologue from the yeast, Candida glabrata

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

    Sampathkumar, Parthasarathy; Kim, Seung Joong; Manglicmot, Danalyn

    2012-10-23

    The nuclear pore complex (NPC), embedded in the nuclear envelope, is a large, dynamic molecular assembly that facilitates exchange of macromolecules between the nucleus and the cytoplasm. The yeast NPC is an eightfold symmetric annular structure composed of {approx}456 polypeptide chains contributed by {approx}30 distinct proteins termed nucleoporins. Nup116, identified only in fungi, plays a central role in both protein import and mRNA export through the NPC. Nup116 is a modular protein with N-terminal 'FG' repeats containing a Gle2p-binding sequence motif and a NPC targeting domain at its C-terminus. We report the crystal structure of the NPC targeting domain ofmore » Candida glabrata Nup116, consisting of residues 882-1034 [CgNup116(882-1034)], at 1.94 {angstrom} resolution. The X-ray structure of CgNup116(882-1034) is consistent with the molecular envelope determined in solution by small-angle X-ray scattering. Structural similarities of CgNup116(882-1034) with homologous domains from Saccharomyces cerevisiae Nup116, S. cerevisiae Nup145N, and human Nup98 are discussed.« less

  10. The intrinsic flexibility of the aptamer targeting the ribosomal protein S8 is a key factor for the molecular recognition.

    PubMed

    Autiero, Ida; Ruvo, Menotti; Improta, Roberto; Vitagliano, Luigi

    2018-04-01

    Aptamers are RNA/DNA biomolecules representing an emerging class of protein interactors and regulators. Despite the growing interest in these molecules, current understanding of chemical-physical basis of their target recognition is limited. Recently, the characterization of the aptamer targeting the protein-S8 has suggested that flexibility plays important functional roles. We investigated the structural versatility of the S8-aptamer by molecular dynamics simulations. Five different simulations have been conducted by varying starting structures and temperatures. The simulation of S8-aptamer complex provides a dynamic view of the contacts occurring at the complex interface. The simulation of the aptamer in ligand-free state indicates that its central region is intrinsically endowed with a remarkable flexibility. Nevertheless, none of the trajectory structures adopts the structure observed in the S8-aptamer complex. The aptamer ligand-bound is very rigid in the simulation carried out at 300 K. A structural transition of this state, providing insights into the aptamer-protein recognition process, is observed in a simulation carried out at 400 K. These data indicate that a key event in the binding is linked to the widening of the central region of the aptamer. Particularly relevant is switch of the A26 base from its ligand-free state to a location that allows the G13-C28 base-pairing. Intrinsic flexibility of the aptamer is essential for partner recognition. Present data indicate that S8 recognizes the aptamer through an induced-fit rather than a population-shift mechanism. The present study provides deeper understanding of the structural basis of the structural versatility of aptamers. Copyright © 2018 Elsevier B.V. All rights reserved.

  11. The nonverbal expression of pride: evidence for cross-cultural recognition.

    PubMed

    Tracy, Jessica L; Robins, Richard W

    2008-03-01

    The present research tests whether recognition for the nonverbal expression of pride generalizes across cultures. Study 1 provided the first evidence for cross-cultural recognition of pride, demonstrating that the expression generalizes across Italy and the United States. Study 2 found that the pride expression generalizes beyond Western cultures; individuals from a preliterate, highly isolated tribe in Burkina Faso, West Africa, reliably recognized pride, regardless of whether it was displayed by African or American targets. These Burkinabe participants were unlikely to have learned the pride expression through cross-cultural transmission, so their recognition suggests that pride may be a human universal. Studies 3 and 4 used drawn figures to systematically manipulate the ethnicity and gender of targets showing the expression, and demonstrated that pride recognition generalizes across male and female targets of African, Asian, and Caucasian descent. Discussion focuses on the implications of the findings for the universality of the pride expression.

  12. ErbB-targeted CAR T-cell immunotherapy of cancer.

    PubMed

    Whilding, Lynsey M; Maher, John

    2015-01-01

    Chimeric antigen receptor (CAR) based immunotherapy has been under development for the last 25 years and is now a promising new treatment modality in the field of cancer immunotherapy. The approach involves genetically engineering T cells to target malignant cells through expression of a bespoke fusion receptor that couples an HLA-independent antigen recognition domain to one or more intracellular T-cell activating modules. Multiple clinical trials are now underway in several centers to investigate CAR T-cell immunotherapy of diverse hematologic and solid tumor types. The most successful results have been achieved in the treatment of patients with B-cell malignancies, in whom several complete and durable responses have been achieved. This review focuses on the preclinical and clinical development of CAR T-cell immunotherapy of solid cancers, targeted against members of the ErbB family.

  13. Differential Recognition Preferences of the Three Src Homology 3 (SH3) Domains from the Adaptor CD2-associated Protein (CD2AP) and Direct Association with Ras and Rab Interactor 3 (RIN3)*

    PubMed Central

    Rouka, Evgenia; Simister, Philip C.; Janning, Melanie; Kumbrink, Joerg; Konstantinou, Tassos; Muniz, João R. C.; Joshi, Dhira; O'Reilly, Nicola; Volkmer, Rudolf; Ritter, Brigitte; Knapp, Stefan; von Delft, Frank; Kirsch, Kathrin H.; Feller, Stephan M.

    2015-01-01

    CD2AP is an adaptor protein involved in membrane trafficking, with essential roles in maintaining podocyte function within the kidney glomerulus. CD2AP contains three Src homology 3 (SH3) domains that mediate multiple protein-protein interactions. However, a detailed comparison of the molecular binding preferences of each SH3 remained unexplored, as well as the discovery of novel interactors. Thus, we studied the binding properties of each SH3 domain to the known interactor Casitas B-lineage lymphoma protein (c-CBL), conducted a peptide array screen based on the recognition motif PxPxPR and identified 40 known or novel candidate binding proteins, such as RIN3, a RAB5-activating guanine nucleotide exchange factor. CD2AP SH3 domains 1 and 2 generally bound with similar characteristics and specificities, whereas the SH3-3 domain bound more weakly to most peptide ligands tested yet recognized an unusually extended sequence in ALG-2-interacting protein X (ALIX). RIN3 peptide scanning arrays revealed two CD2AP binding sites, recognized by all three SH3 domains, but SH3-3 appeared non-functional in precipitation experiments. RIN3 recruited CD2AP to RAB5a-positive early endosomes via these interaction sites. Permutation arrays and isothermal titration calorimetry data showed that the preferred binding motif is Px(P/A)xPR. Two high-resolution crystal structures (1.65 and 1.11 Å) of CD2AP SH3-1 and SH3-2 solved in complex with RIN3 epitopes 1 and 2, respectively, indicated that another extended motif is relevant in epitope 2. In conclusion, we have discovered novel interaction candidates for CD2AP and characterized subtle yet significant differences in the recognition preferences of its three SH3 domains for c-CBL, ALIX, and RIN3. PMID:26296892

  14. Novel Kinase Inhibitors Targeting the PH Domain of AKT for Preventing and Treating Cancer | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute's Medical Oncology Branch is seeking statements of capability or interest from parties interested in licensing and co-development collaborative research to further develop, evaluate, or commercialize novel kinase inhibitors targeting the PH domain of AKT.

  15. Role of interfacial water molecules in proline-rich ligand recognition by the Src homology 3 domain of Abl.

    PubMed

    Palencia, Andres; Camara-Artigas, Ana; Pisabarro, M Teresa; Martinez, Jose C; Luque, Irene

    2010-01-22

    The interaction of Abl-Src homology 3 domain (SH3) with the high affinity peptide p41 is the most notable example of the inconsistency existing between the currently accepted description of SH3 complexes and their binding thermodynamic signature. We had previously hypothesized that the presence of interfacial water molecules is partially responsible for this thermodynamic behavior. We present here a thermodynamic, structural, and molecular dynamics simulation study of the interaction of p41 with Abl-SH3 and a set of mutants designed to alter the water-mediated interaction network. Our results provide a detailed description of the dynamic properties of the interfacial water molecules and a molecular interpretation of the thermodynamic effects elicited by the mutations in terms of the modulation of the water-mediated hydrogen bond network. In the light of these results, a new dual binding mechanism is proposed that provides a better description of proline-rich ligand recognition by Abl-SH3 and that has important implications for rational design.

  16. Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system

    PubMed Central

    Elmore, Joshua R.; Sheppard, Nolan F.; Ramia, Nancy; Deighan, Trace; Li, Hong; Terns, Rebecca M.; Terns, Michael P.

    2016-01-01

    CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID:26848045

  17. Domain Adaptation for Pedestrian Detection Based on Prediction Consistency

    PubMed Central

    Huan-ling, Tang; Zhi-yong, An

    2014-01-01

    Pedestrian detection is an active area of research in computer vision. It remains a quite challenging problem in many applications where many factors cause a mismatch between source dataset used to train the pedestrian detector and samples in the target scene. In this paper, we propose a novel domain adaptation model for merging plentiful source domain samples with scared target domain samples to create a scene-specific pedestrian detector that performs as well as rich target domain simples are present. Our approach combines the boosting-based learning algorithm with an entropy-based transferability, which is derived from the prediction consistency with the source classifications, to selectively choose the samples showing positive transferability in source domains to the target domain. Experimental results show that our approach can improve the detection rate, especially with the insufficient labeled data in target scene. PMID:25013850

  18. ATRX ADD domain links an atypical histone methylation recognition mechanism to human mental-retardation syndrome

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

    Iwase, Shigeki; Xiang, Bin; Ghosh, Sharmistha

    ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket,more » which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.« less

  19. ATRX ADD Domain Links an Atypical Histone Methylation Recognition Mechanism to Human Mental-Retardation Syndrome

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

    S Iwase; B Xiang; S Ghosh

    ATR-X (alpha-thalassemia/mental retardation, X-linked) syndrome is a human congenital disorder that causes severe intellectual disabilities. Mutations in the ATRX gene, which encodes an ATP-dependent chromatin-remodeler, are responsible for the syndrome. Approximately 50% of the missense mutations in affected persons are clustered in a cysteine-rich domain termed ADD (ATRX-DNMT3-DNMT3L, ADD{sub ATRX}), whose function has remained elusive. Here we identify ADD{sub ATRX} as a previously unknown histone H3-binding module, whose binding is promoted by lysine 9 trimethylation (H3K9me3) but inhibited by lysine 4 trimethylation (H3K4me3). The cocrystal structure of ADD{sub ATRX} bound to H3{sub 1-15}K9me3 peptide reveals an atypical composite H3K9me3-binding pocket,more » which is distinct from the conventional trimethyllysine-binding aromatic cage. Notably, H3K9me3-pocket mutants and ATR-X syndrome mutants are defective in both H3K9me3 binding and localization at pericentromeric heterochromatin; thus, we have discovered a unique histone-recognition mechanism underlying the ATR-X etiology.« less

  20. Using eye movements as an index of implicit face recognition in autism spectrum disorder.

    PubMed

    Hedley, Darren; Young, Robyn; Brewer, Neil

    2012-10-01

    Individuals with an autism spectrum disorder (ASD) typically show impairment on face recognition tasks. Performance has usually been assessed using overt, explicit recognition tasks. Here, a complementary method involving eye tracking was used to examine implicit face recognition in participants with ASD and in an intelligence quotient-matched non-ASD control group. Differences in eye movement indices between target and foil faces were used as an indicator of implicit face recognition. Explicit face recognition was assessed using old-new discrimination and reaction time measures. Stimuli were faces of studied (target) or unfamiliar (foil) persons. Target images at test were either identical to the images presented at study or altered by changing the lighting, pose, or by masking with visual noise. Participants with ASD performed worse than controls on the explicit recognition task. Eye movement-based measures, however, indicated that implicit recognition may not be affected to the same degree as explicit recognition. Autism Res 2012, 5: 363-379. © 2012 International Society for Autism Research, Wiley Periodicals, Inc. © 2012 International Society for Autism Research, Wiley Periodicals, Inc.

  1. Ubiquitin Regulates Caspase Recruitment Domain-mediated Signaling by Nucleotide-binding Oligomerization Domain-containing Proteins NOD1 and NOD2*

    PubMed Central

    Ver Heul, Aaron M.; Fowler, C. Andrew; Ramaswamy, S.; Piper, Robert C.

    2013-01-01

    NOD1 and NOD2 (nucleotide-binding oligomerization domain-containing proteins) are intracellular pattern recognition receptors that activate inflammation and autophagy. These pathways rely on the caspase recruitment domains (CARDs) within the receptors, which serve as protein interaction platforms that coordinately regulate immune signaling. We show that NOD1 CARD binds ubiquitin (Ub), in addition to directly binding its downstream targets receptor-interacting protein kinase 2 (RIP2) and autophagy-related protein 16-1 (ATG16L1). NMR spectroscopy and structure-guided mutagenesis identified a small hydrophobic surface of NOD1 CARD that binds Ub. In vitro, Ub competes with RIP2 for association with NOD1 CARD. In vivo, we found that the ligand-stimulated activity of NOD1 with a mutant CARD lacking Ub binding but retaining ATG16L1 and RIP2 binding is increased relative to wild-type NOD1. Likewise, point mutations in the tandem NOD2 CARDs at positions analogous to the surface residues defining the Ub interface on NOD1 resulted in loss of Ub binding and increased ligand-stimulated NOD2 signaling. These data suggest that Ub binding provides a negative feedback loop upon NOD-dependent activation of RIP2. PMID:23300079

  2. A Novel Non-canonical Forkhead-associated (FHA) Domain-binding Interface Mediates the Interaction between Rad53 and Dbf4 Proteins*

    PubMed Central

    Matthews, Lindsay A.; Selvaratnam, Rajeevan; Jones, Darryl R.; Akimoto, Madoka; McConkey, Brendan J.; Melacini, Giuseppe; Duncker, Bernard P.; Guarné, Alba

    2014-01-01

    Forkhead-associated (FHA) and BRCA1 C-terminal (BRCT) domains are overrepresented in DNA damage and replication stress response proteins. They function primarily as phosphoepitope recognition modules but can also mediate non-canonical interactions. The latter are rare, and only a few have been studied at a molecular level. We have identified a crucial non-canonical interaction between the N-terminal FHA1 domain of the checkpoint effector kinase Rad53 and the BRCT domain of the regulatory subunit of the Dbf4-dependent kinase that is critical to suppress late origin firing and to stabilize stalled forks during replication stress. The Rad53-Dbf4 interaction is phosphorylation-independent and involves a novel non-canonical interface on the FHA1 domain. Mutations within this surface result in hypersensitivity to genotoxic stress. Importantly, this surface is not conserved in the FHA2 domain of Rad53, suggesting that the FHA domains of Rad53 gain specificity by engaging additional interaction interfaces beyond their phosphoepitope-binding site. In general, our results point to FHA domains functioning as complex logic gates rather than mere phosphoepitope-targeting modules. PMID:24285546

  3. Carbohydrate recognition by the rhamnose-binding lectin SUL-I with a novel three-domain structure isolated from the venom of globiferous pedicellariae of the flower sea urchin Toxopneustes pileolus.

    PubMed

    Hatakeyama, Tomomitsu; Ichise, Ayaka; Unno, Hideaki; Goda, Shuichiro; Oda, Tatsuya; Tateno, Hiroaki; Hirabayashi, Jun; Sakai, Hitomi; Nakagawa, Hideyuki

    2017-08-01

    The globiferous pedicellariae of the venomous sea urchin Toxopneustes pileolus contains several biologically active proteins. We have cloned the cDNA of one of the toxin components, SUL-I, which is a rhamnose-binding lectin (RBL) that acts as a mitogen through binding to carbohydrate chains on target cells. Recombinant SUL-I (rSUL-I) was produced in Escherichia coli cells, and its carbohydrate-binding specificity was examined with the glycoconjugate microarray analysis, which suggested that potential target carbohydrate structures are galactose-terminated N-glycans. rSUL-I exhibited mitogenic activity for murine splenocyte cells and toxicity against Vero cells. The three-dimensional structure of the rSUL-I/l-rhamnose complex was determined by X-ray crystallographic analysis at a 1.8 Å resolution. The overall structure of rSUL-I is composed of three distinctive domains with a folding structure similar to those of CSL3, a RBL from chum salmon (Oncorhynchus keta) eggs. The bound l-rhamnose molecules are mainly recognized by rSUL-I through hydrogen bonds between its 2-, 3-, and 4-hydroxy groups and Asp, Asn, and Glu residues in the binding sites, while Tyr and Ser residues participate in the recognition mechanism. It was also inferred that SUL-I may form a dimer in solution based on the molecular size estimated via dynamic light scattering as well as possible contact regions in its crystal structure. © 2017 The Protein Society.

  4. Recognition of face and non-face stimuli in autistic spectrum disorder.

    PubMed

    Arkush, Leo; Smith-Collins, Adam P R; Fiorentini, Chiara; Skuse, David H

    2013-12-01

    The ability to remember faces is critical for the development of social competence. From childhood to adulthood, we acquire a high level of expertise in the recognition of facial images, and neural processes become dedicated to sustaining competence. Many people with autism spectrum disorder (ASD) have poor face recognition memory; changes in hairstyle or other non-facial features in an otherwise familiar person affect their recollection skills. The observation implies that they may not use the configuration of the inner face to achieve memory competence, but bolster performance in other ways. We aimed to test this hypothesis by comparing the performance of a group of high-functioning unmedicated adolescents with ASD and a matched control group on a "surprise" face recognition memory task. We compared their memory for unfamiliar faces with their memory for images of houses. To evaluate the role that is played by peripheral cues in assisting recognition memory, we cropped both sets of pictures, retaining only the most salient central features. ASD adolescents had poorer recognition memory for faces than typical controls, but their recognition memory for houses was unimpaired. Cropping images of faces did not disproportionately influence their recall accuracy, relative to controls. House recognition skills (cropped and uncropped) were similar in both groups. In the ASD group only, performance on both sets of task was closely correlated, implying that memory for faces and other complex pictorial stimuli is achieved by domain-general (non-dedicated) cognitive mechanisms. Adolescents with ASD apparently do not use domain-specialized processing of inner facial cues to support face recognition memory. © 2013 International Society for Autism Research, Wiley Periodicals, Inc.

  5. Object recognition with hierarchical discriminant saliency networks.

    PubMed

    Han, Sunhyoung; Vasconcelos, Nuno

    2014-01-01

    The benefits of integrating attention and object recognition are investigated. While attention is frequently modeled as a pre-processor for recognition, we investigate the hypothesis that attention is an intrinsic component of recognition and vice-versa. This hypothesis is tested with a recognition model, the hierarchical discriminant saliency network (HDSN), whose layers are top-down saliency detectors, tuned for a visual class according to the principles of discriminant saliency. As a model of neural computation, the HDSN has two possible implementations. In a biologically plausible implementation, all layers comply with the standard neurophysiological model of visual cortex, with sub-layers of simple and complex units that implement a combination of filtering, divisive normalization, pooling, and non-linearities. In a convolutional neural network implementation, all layers are convolutional and implement a combination of filtering, rectification, and pooling. The rectification is performed with a parametric extension of the now popular rectified linear units (ReLUs), whose parameters can be tuned for the detection of target object classes. This enables a number of functional enhancements over neural network models that lack a connection to saliency, including optimal feature denoising mechanisms for recognition, modulation of saliency responses by the discriminant power of the underlying features, and the ability to detect both feature presence and absence. In either implementation, each layer has a precise statistical interpretation, and all parameters are tuned by statistical learning. Each saliency detection layer learns more discriminant saliency templates than its predecessors and higher layers have larger pooling fields. This enables the HDSN to simultaneously achieve high selectivity to target object classes and invariance. The performance of the network in saliency and object recognition tasks is compared to those of models from the biological and

  6. A fusion-protein approach enabling mammalian cell production of tumor targeting protein domains for therapeutic development.

    PubMed

    Hu, Jia; Chen, Xiang; Zhang, Xuhua; Yuan, Xiaopeng; Yang, Mingjuan; Dai, Hui; Yang, Wei; Zhou, Qinghua; Wen, Weihong; Wang, Qirui; Qin, Weijun; Zhao, Aizhi

    2018-05-01

    A single chain Fv fragment (scFv) is a fusion of the variable regions of heavy (V H ) and light (V L ) chains of immunoglobulins. They are important elements of chimeric antigen receptors for cancer therapy. We sought to produce a panel of 16 extracellular protein domains of tumor markers for use in scFv yeast library screenings. A series of vectors comprising various combinations of expression elements was made, but expression was unpredictable and more than half of the protein domains could not be produced using any of the constructs. Here we describe a novel fusion expression system based on mouse TEM7 (tumor endothelial marker 7), which could facilitate protein expression. With this approach we could produce all but one of the tumor marker domains that could not otherwise be expressed. In addition, we demonstrated that the tumor associated antigen hFZD10 produced as a fusion protein with mTEM7 could be used to enrich scFv antibodies from a yeast display library. Collectively our study demonstrates the potential of specific fusion proteins based on mTEM7 in enabling mammalian cell production of tumor targeting protein domains for therapeutic development. © 2018 The Protein Society.

  7. Targeting lysine specific demethylase 4A (KDM4A) tandem TUDOR domain - A fragment based approach.

    PubMed

    Upadhyay, Anup K; Judge, Russell A; Li, Leiming; Pithawalla, Ron; Simanis, Justin; Bodelle, Pierre M; Marin, Violeta L; Henry, Rodger F; Petros, Andrew M; Sun, Chaohong

    2018-06-01

    The tandem TUDOR domains present in the non-catalytic C-terminal half of the KDM4A, 4B and 4C enzymes play important roles in regulating their chromatin localizations and substrate specificities. They achieve this regulatory role by binding to different tri-methylated lysine residues on histone H3 (H3-K4me3, H3-K23me3) and histone H4 (H4-K20me3) depending upon the specific chromatin environment. In this work, we have used a 2D-NMR based fragment screening approach to identify a novel fragment (1a), which binds to the KDM4A-TUDOR domain and shows modest competition with H3-K4me3 binding in biochemical as well as in vitro cell based assays. A co-crystal structure of KDM4A TUDOR domain in complex with 1a shows that the fragment binds stereo-specifically to the methyl lysine binding pocket forming a network of strong hydrogen bonds and hydrophobic interactions. We anticipate that the fragment 1a can be further developed into a novel allosteric inhibitor of the KDM4 family of enzymes through targeting their C-terminal tandem TUDOR domain. Copyright © 2018 Elsevier Ltd. All rights reserved.

  8. Development of a sonar-based object recognition system

    NASA Astrophysics Data System (ADS)

    Ecemis, Mustafa Ihsan

    2001-02-01

    Sonars are used extensively in mobile robotics for obstacle detection, ranging and avoidance. However, these range-finding applications do not exploit the full range of information carried in sonar echoes. In addition, mobile robots need robust object recognition systems. Therefore, a simple and robust object recognition system using ultrasonic sensors may have a wide range of applications in robotics. This dissertation develops and analyzes an object recognition system that uses ultrasonic sensors of the type commonly found on mobile robots. Three principal experiments are used to test the sonar recognition system: object recognition at various distances, object recognition during unconstrained motion, and softness discrimination. The hardware setup, consisting of an inexpensive Polaroid sonar and a data acquisition board, is described first. The software for ultrasound signal generation, echo detection, data collection, and data processing is then presented. Next, the dissertation describes two methods to extract information from the echoes, one in the frequency domain and the other in the time domain. The system uses the fuzzy ARTMAP neural network to recognize objects on the basis of the information content of their echoes. In order to demonstrate that the performance of the system does not depend on the specific classification method being used, the K- Nearest Neighbors (KNN) Algorithm is also implemented. KNN yields a test accuracy similar to fuzzy ARTMAP in all experiments. Finally, the dissertation describes a method for extracting features from the envelope function in order to reduce the dimension of the input vector used by the classifiers. Decreasing the size of the input vectors reduces the memory requirements of the system and makes it run faster. It is shown that this method does not affect the performance of the system dramatically and is more appropriate for some tasks. The results of these experiments demonstrate that sonar can be used to develop

  9. Structural plasticity of the TDRD3 Tudor domain probed by a fragment screening hit.

    PubMed

    Liu, Jiuyang; Zhang, Shuya; Liu, Mingqing; Liu, Yaqian; Nshogoza, Gilbert; Gao, Jia; Ma, Rongsheng; Yang, Yang; Wu, Jihui; Zhang, Jiahai; Li, Fudong; Ruan, Ke

    2018-04-12

    As a reader of di-methylated arginine on various proteins, such as histone, RNA polymerase II, PIWI and Fragile X mental retardation protein, the Tudor domain of Tudor domain-containing protein 3 (TDRD3) mediates transcriptional activation in nucleus and formation of stress granules in the cytoplasm. Despite the TDRD3 implication in cancer cell proliferation and invasion, warheads to block the di-methylated arginine recognition pocket of the TDRD3 Tudor domain have not yet been uncovered. Here we identified 14 small molecule hits against the TDRD3 Tudor domain through NMR fragment-based screening. These hits were further cross-validated by using competitive fluorescence polarization and isothermal titration calorimetry experiments. The crystal structure of the TDRD3 Tudor domain in complex with hit 1 reveals a distinct binding mode from the nature substrate. Hit 1 protrudes into the aromatic cage of the TDRD3 Tudor domain, where the aromatic residues are tilted to accommodate a sandwich-like π-π interaction. The side chain of the conserved residue N596 swings away 3.1 Å to form a direct hydrogen bond with hit 1. Moreover, this compound shows a decreased affinity against the single Tudor domain of survival motor neuron protein, but no detectable binding to neither the tandem Tudor domain of TP53-binding protein 1 nor the extended Tudor domain of staphylococcal nuclease domain-containing protein 1. Our work depicts the structural plasticity of the TDRD3 Tudor domain and paves the way for the subsequent structure-guided discovery of selective inhibitors targeting Tudor domains. Structural data are available in the PDB under the accession number 5YJ8. © 2018 Federation of European Biochemical Societies.

  10. Domain Adaptation with Conditional Transferable Components

    PubMed Central

    Gong, Mingming; Zhang, Kun; Liu, Tongliang; Tao, Dacheng; Glymour, Clark; Schölkopf, Bernhard

    2017-01-01

    Domain adaptation arises in supervised learning when the training (source domain) and test (target domain) data have different distributions. Let X and Y denote the features and target, respectively, previous work on domain adaptation mainly considers the covariate shift situation where the distribution of the features P(X) changes across domains while the conditional distribution P(Y∣X) stays the same. To reduce domain discrepancy, recent methods try to find invariant components T(X) that have similar P(T(X)) on different domains by explicitly minimizing a distribution discrepancy measure. However, it is not clear if P(Y∣T(X)) in different domains is also similar when P(Y∣X) changes. Furthermore, transferable components do not necessarily have to be invariant. If the change in some components is identifiable, we can make use of such components for prediction in the target domain. In this paper, we focus on the case where P(X∣Y) and P(Y) both change in a causal system in which Y is the cause for X. Under appropriate assumptions, we aim to extract conditional transferable components whose conditional distribution P(T(X)∣Y) is invariant after proper location-scale (LS) transformations, and identify how P(Y) changes between domains simultaneously. We provide theoretical analysis and empirical evaluation on both synthetic and real-world data to show the effectiveness of our method. PMID:28239433

  11. Constructive autoassociative neural network for facial recognition.

    PubMed

    Fernandes, Bruno J T; Cavalcanti, George D C; Ren, Tsang I

    2014-01-01

    Autoassociative artificial neural networks have been used in many different computer vision applications. However, it is difficult to define the most suitable neural network architecture because this definition is based on previous knowledge and depends on the problem domain. To address this problem, we propose a constructive autoassociative neural network called CANet (Constructive Autoassociative Neural Network). CANet integrates the concepts of receptive fields and autoassociative memory in a dynamic architecture that changes the configuration of the receptive fields by adding new neurons in the hidden layer, while a pruning algorithm removes neurons from the output layer. Neurons in the CANet output layer present lateral inhibitory connections that improve the recognition rate. Experiments in face recognition and facial expression recognition show that the CANet outperforms other methods presented in the literature.

  12. Structural Motifs Involved in Ubiquitin-Mediated Processing of the NF-κB Precursor p105: Roles of the Glycine-Rich Region and a Downstream Ubiquitination Domain

    PubMed Central

    Orian, Amir; Schwartz, Alan L.; Israël, Alain; Whiteside, Simon; Kahana, Chaim; Ciechanover, Aaron

    1999-01-01

    The ubiquitin proteolytic system plays a major role in a variety of basic cellular processes. In the majority of these processes, the target proteins are completely degraded. In one exceptional case, generation of the p50 subunit of the transcriptional regulator NF-κB, the precursor protein p105 is processed in a limited manner: the N-terminal domain yields the p50 subunit, whereas the C-terminal domain is degraded. The identity of the mechanisms involved in this unique process have remained elusive. It has been shown that a Gly-rich region (GRR) at the C-terminal domain of p50 is an important processing signal. Here we show that the GRR does not interfere with conjugation of ubiquitin to p105 but probably does interfere with the processing of the ubiquitin-tagged precursor by the 26S proteasome. Structural analysis reveals that a short sequence containing a few Gly residues and a single essential Ala is sufficient to generate p50. Mechanistically, the presence of the GRR appears to stop further degradation of p50 and to stabilize the molecule. It appears that the localization of the GRR within p105 plays an important role in directing processing: transfer of the GRR within p105 or insertion of the GRR into homologous or heterologous proteins is not sufficient to promote processing in most cases, which is probably due to the requirement for an additional specific ubiquitination and/or recognition domain(s). Indeed, we have shown that amino acid residues 441 to 454 are important for processing. In particular, both Lys 441 and Lys 442 appear to serve as major ubiquitination targets, while residues 446 to 454 are independently important for processing and may serve as the ubiquitin ligase recognition motif. PMID:10207090

  13. Ebolavirus Nucleoprotein C-Termini Potently Attract Single Domain Antibodies Enabling Monoclonal Affinity Reagent Sandwich Assay (MARSA) Formulation

    PubMed Central

    Sherwood, Laura J.; Hayhurst, Andrew

    2013-01-01

    Background Antigen detection assays can play an important part in environmental surveillance and diagnostics for emerging threats. We are interested in accelerating assay formulation; targeting the agents themselves to bypass requirements for a priori genome information or surrogates. Previously, using in vitro affinity reagent selection on Marburg virus we rapidly established monoclonal affinity reagent sandwich assay (MARSA) where one recombinant antibody clone was both captor and tracer for polyvalent nucleoprotein (NP). Hypothesizing that the closely related Ebolavirus genus may share the same Achilles' heel, we redirected the scheme to see whether similar assays could be delivered and began to explore their mechanism. Methods and Findings In parallel we selected panels of llama single domain antibodies (sdAb) from a semi-synthetic library against Zaire, Sudan, Ivory Coast, and Reston Ebola viruses. Each could perform as both captor and tracer in the same antigen sandwich capture assay thereby forming MARSAs. All sdAb were specific for NP and those tested required the C-terminal domain for recognition. Several clones were cross-reactive, indicating epitope conservation across the Ebolavirus genus. Analysis of two immune shark sdAb revealed they also targeted the C-terminal domain, and could be similarly employed, yet were less sensitive than a comparable llama sdAb despite stemming from immune selections. Conclusions The C-terminal domain of Ebolavirus NP is a strong attractant for antibodies and enables sensitive sandwich immunoassays to be rapidly generated using a single antibody clone. The polyvalent nature of nucleocapsid borne NP and display of the C-terminal region likely serves as a bountiful affinity sink during selections, and a highly avid target for subsequent immunoassay capture. Combined with the high degree of amino acid conservation through 37 years and across wide geographies, this domain makes an ideal handle for monoclonal affinity reagent

  14. A Component-Based Vocabulary-Extensible Sign Language Gesture Recognition Framework.

    PubMed

    Wei, Shengjing; Chen, Xiang; Yang, Xidong; Cao, Shuai; Zhang, Xu

    2016-04-19

    Sign language recognition (SLR) can provide a helpful tool for the communication between the deaf and the external world. This paper proposed a component-based vocabulary extensible SLR framework using data from surface electromyographic (sEMG) sensors, accelerometers (ACC), and gyroscopes (GYRO). In this framework, a sign word was considered to be a combination of five common sign components, including hand shape, axis, orientation, rotation, and trajectory, and sign classification was implemented based on the recognition of five components. Especially, the proposed SLR framework consisted of two major parts. The first part was to obtain the component-based form of sign gestures and establish the code table of target sign gesture set using data from a reference subject. In the second part, which was designed for new users, component classifiers were trained using a training set suggested by the reference subject and the classification of unknown gestures was performed with a code matching method. Five subjects participated in this study and recognition experiments under different size of training sets were implemented on a target gesture set consisting of 110 frequently-used Chinese Sign Language (CSL) sign words. The experimental results demonstrated that the proposed framework can realize large-scale gesture set recognition with a small-scale training set. With the smallest training sets (containing about one-third gestures of the target gesture set) suggested by two reference subjects, (82.6 ± 13.2)% and (79.7 ± 13.4)% average recognition accuracy were obtained for 110 words respectively, and the average recognition accuracy climbed up to (88 ± 13.7)% and (86.3 ± 13.7)% when the training set included 50~60 gestures (about half of the target gesture set). The proposed framework can significantly reduce the user's training burden in large-scale gesture recognition, which will facilitate the implementation of a practical SLR system.

  15. Single-Domain Antibodies Targeting Neuraminidase Protect against an H5N1 Influenza Virus Challenge

    PubMed Central

    Cardoso, Francisco Miguel; Ibañez, Lorena Itatí; Van den Hoecke, Silvie; De Baets, Sarah; Smet, Anouk; Roose, Kenny; Schepens, Bert; Descamps, Francis J.; Fiers, Walter; Muyldermans, Serge

    2014-01-01

    ABSTRACT Influenza virus neuraminidase (NA) is an interesting target of small-molecule antiviral drugs. We isolated a set of H5N1 NA-specific single-domain antibodies (N1-VHHm) and evaluated their in vitro and in vivo antiviral potential. Two of them inhibited the NA activity and in vitro replication of clade 1 and 2 H5N1 viruses. We then generated bivalent derivatives of N1-VHHm by two methods. First, we made N1-VHHb by genetically joining two N1-VHHm moieties with a flexible linker. Second, bivalent N1-VHH-Fc proteins were obtained by genetic fusion of the N1-VHHm moiety with the crystallizable region of mouse IgG2a (Fc). The in vitro antiviral potency against H5N1 of both bivalent N1-VHHb formats was 30- to 240-fold higher than that of their monovalent counterparts, with 50% inhibitory concentrations in the low nanomolar range. Moreover, single-dose prophylactic treatment with bivalent N1-VHHb or N1-VHH-Fc protected BALB/c mice against a lethal challenge with H5N1 virus, including an oseltamivir-resistant H5N1 variant. Surprisingly, an N1-VHH-Fc fusion without in vitro NA-inhibitory or antiviral activity also protected mice against an H5N1 challenge. Virus escape selection experiments indicated that one amino acid residue close to the catalytic site is required for N1-VHHm binding. We conclude that single-domain antibodies directed against influenza virus NA protect against H5N1 virus infection, and when engineered with a conventional Fc domain, they can do so in the absence of detectable NA-inhibitory activity. IMPORTANCE Highly pathogenic H5N1 viruses are a zoonotic threat. Outbreaks of avian influenza caused by these viruses occur in many parts of the world and are associated with tremendous economic loss, and these viruses can cause very severe disease in humans. In such cases, small-molecule inhibitors of the viral NA are among the few treatment options for patients. However, treatment with such drugs often results in the emergence of resistant viruses

  16. Domain adaptation via transfer component analysis.

    PubMed

    Pan, Sinno Jialin; Tsang, Ivor W; Kwok, James T; Yang, Qiang

    2011-02-01

    Domain adaptation allows knowledge from a source domain to be transferred to a different but related target domain. Intuitively, discovering a good feature representation across domains is crucial. In this paper, we first propose to find such a representation through a new learning method, transfer component analysis (TCA), for domain adaptation. TCA tries to learn some transfer components across domains in a reproducing kernel Hilbert space using maximum mean miscrepancy. In the subspace spanned by these transfer components, data properties are preserved and data distributions in different domains are close to each other. As a result, with the new representations in this subspace, we can apply standard machine learning methods to train classifiers or regression models in the source domain for use in the target domain. Furthermore, in order to uncover the knowledge hidden in the relations between the data labels from the source and target domains, we extend TCA in a semisupervised learning setting, which encodes label information into transfer components learning. We call this extension semisupervised TCA. The main contribution of our work is that we propose a novel dimensionality reduction framework for reducing the distance between domains in a latent space for domain adaptation. We propose both unsupervised and semisupervised feature extraction approaches, which can dramatically reduce the distance between domain distributions by projecting data onto the learned transfer components. Finally, our approach can handle large datasets and naturally lead to out-of-sample generalization. The effectiveness and efficiency of our approach are verified by experiments on five toy datasets and two real-world applications: cross-domain indoor WiFi localization and cross-domain text classification.

  17. Automatic integration of social information in emotion recognition.

    PubMed

    Mumenthaler, Christian; Sander, David

    2015-04-01

    This study investigated the automaticity of the influence of social inference on emotion recognition. Participants were asked to recognize dynamic facial expressions of emotion (fear or anger in Experiment 1 and blends of fear and surprise or of anger and disgust in Experiment 2) in a target face presented at the center of a screen while a subliminal contextual face appearing in the periphery expressed an emotion (fear or anger) or not (neutral) and either looked at the target face or not. Results of Experiment 1 revealed that recognition of the target emotion of fear was improved when a subliminal angry contextual face gazed toward-rather than away from-the fearful face. We replicated this effect in Experiment 2, in which facial expression blends of fear and surprise were more often and more rapidly categorized as expressing fear when the subliminal contextual face expressed anger and gazed toward-rather than away from-the target face. With the contextual face appearing for 30 ms in total, including only 10 ms of emotion expression, and being immediately masked, our data provide the first evidence that social influence on emotion recognition can occur automatically. (c) 2015 APA, all rights reserved).

  18. Prediction of glycolipid-binding domains from the amino acid sequence of lipid raft-associated proteins: application to HpaA, a protein involved in the adhesion of Helicobacter pylori to gastrointestinal cells.

    PubMed

    Fantini, Jacques; Garmy, Nicolas; Yahi, Nouara

    2006-09-12

    Protein-glycolipid interactions mediate the attachment of various pathogens to the host cell surface as well as the association of numerous cellular proteins with lipid rafts. Thus, it is of primary importance to identify the protein domains involved in glycolipid recognition. Using structure similarity searches, we could identify a common glycolipid-binding domain in the three-dimensional structure of several proteins known to interact with lipid rafts. Yet the three-dimensional structure of most raft-targeted proteins is still unknown. In the present study, we have identified a glycolipid-binding domain in the amino acid sequence of a bacterial adhesin (Helicobacter pylori adhesin A, HpaA). The prediction was based on the major properties of the glycolipid-binding domains previously characterized by structural searches. A short (15-mer) synthetic peptide corresponding to this putative glycolipid-binding domain was synthesized, and we studied its interaction with glycolipid monolayers at the air-water interface. The synthetic HpaA peptide recognized LacCer but not Gb3. This glycolipid specificity was in line with that of the whole bacterium. Molecular modeling studies gave some insights into this high selectivity of interaction. It also suggested that Phe147 in HpaA played a key role in LacCer recognition, through sugar-aromatic CH-pi stacking interactions with the hydrophobic side of the galactose ring of LacCer. Correspondingly, the replacement of Phe147 with Ala strongly affected LacCer recognition, whereas substitution with Trp did not. Our method could be used to identify glycolipid-binding domains in microbial and cellular proteins interacting with lipid shells, rafts, and other specialized membrane microdomains.

  19. ARCH: Adaptive recurrent-convolutional hybrid networks for long-term action recognition

    PubMed Central

    Xin, Miao; Zhang, Hong; Wang, Helong; Sun, Mingui; Yuan, Ding

    2017-01-01

    Recognition of human actions from digital video is a challenging task due to complex interfering factors in uncontrolled realistic environments. In this paper, we propose a learning framework using static, dynamic and sequential mixed features to solve three fundamental problems: spatial domain variation, temporal domain polytrope, and intra- and inter-class diversities. Utilizing a cognitive-based data reduction method and a hybrid “network upon networks” architecture, we extract human action representations which are robust against spatial and temporal interferences and adaptive to variations in both action speed and duration. We evaluated our method on the UCF101 and other three challenging datasets. Our results demonstrated a superior performance of the proposed algorithm in human action recognition. PMID:29290647

  20. Laser range profiling for small target recognition

    NASA Astrophysics Data System (ADS)

    Steinvall, Ove; Tulldahl, Michael

    2017-03-01

    Long range identification (ID) or ID at closer range of small targets has its limitations in imaging due to the demand for very high-transverse sensor resolution. This is, therefore, a motivation to look for one-dimensional laser techniques for target ID. These include laser vibrometry and laser range profiling. Laser vibrometry can give good results, but is not always robust as it is sensitive to certain vibrating parts on the target being in the field of view. Laser range profiling is attractive because the maximum range can be substantial, especially for a small laser beam width. A range profiler can also be used in a scanning mode to detect targets within a certain sector. The same laser can also be used for active imaging when the target comes closer and is angularly resolved. Our laser range profiler is based on a laser with a pulse width of 6 ns (full width half maximum). This paper will show both experimental and simulated results for laser range profiling of small boats out to a 6 to 7-km range and a unmanned arrial vehicle (UAV) mockup at close range (1.3 km). The naval experiments took place in the Baltic Sea using many other active and passive electro-optical sensors in addition to the profiling system. The UAV experiments showed the need for a high-range resolution, thus we used a photon counting system in addition to the more conventional profiler used in the naval experiments. This paper shows the influence of target pose and range resolution on the capability of classification. The typical resolution (in our case 0.7 m) obtainable with a conventional range finder type of sensor can be used for large target classification with a depth structure over 5 to 10 m or more, but for smaller targets such as a UAV a high resolution (in our case 7.5 mm) is needed to reveal depth structures and surface shapes. This paper also shows the need for 3-D target information to build libraries for comparison of measured and simulated range profiles. At closer ranges

  1. Recognition Imaging of Acetylated Chromatin Using a DNA Aptamer

    PubMed Central

    Lin, Liyun; Fu, Qiang; Williams, Berea A.R.; Azzaz, Abdelhamid M.; Shogren-Knaak, Michael A.; Chaput, John C.; Lindsay, Stuart

    2009-01-01

    Histone acetylation plays an important role in the regulation of gene expression. A DNA aptamer generated by in vitro selection to be highly specific for histone H4 protein acetylated at lysine 16 was used as a recognition element for atomic force microscopy-based recognition imaging of synthetic nucleosomal arrays with precisely controlled acetylation. The aptamer proved to be reasonably specific at recognizing acetylated histones, with recognition efficiencies of 60% on-target and 12% off-target. Though this selectivity is much poorer than the >2000:1 equilibrium specificity of the aptamer, it is a large improvement on the performance of a ChIP-quality antibody, which is not selective at all in this application, and it should permit high-fidelity recognition with repeated imaging. The ability to image the precise location of posttranslational modifications may permit nanometer-scale investigation of their effect on chromatin structure. PMID:19751687

  2. Glucose enhancement of a facial recognition task in young adults.

    PubMed

    Metzger, M M

    2000-02-01

    Numerous studies have reported that glucose administration enhances memory processes in both elderly and young adult subjects. Although these studies have utilized a variety of procedures and paradigms, investigations of both young and elderly subjects have typically used verbal tasks (word list recall, paragraph recall, etc.). In the present study, the effect of glucose consumption on a nonverbal, facial recognition task in young adults was examined. Lemonade sweetened with either glucose (50 g) or saccharin (23.7 mg) was consumed by college students (mean age of 21.1 years) 15 min prior to a facial recognition task. The task consisted of a familiarization phase in which subjects were presented with "target" faces, followed immediately by a recognition phase in which subjects had to identify the targets among a random array of familiar target and novel "distractor" faces. Statistical analysis indicated that there were no differences on hit rate (target identification) for subjects who consumed either saccharin or glucose prior to the test. However, further analyses revealed that subjects who consumed glucose committed significantly fewer false alarms and had (marginally) higher d-prime scores (a signal detection measure) compared to subjects who consumed saccharin prior to the test. These results parallel a previous report demonstrating glucose enhancement of a facial recognition task in probable Alzheimer's patients; however, this is believed to be the first demonstration of glucose enhancement for a facial recognition task in healthy, young adults.

  3. Recognition of Acyl Carrier Proteins by Ketoreductases in Assembly Line Polyketide Synthases

    PubMed Central

    Ostrowski, Matthew P.; Cane, David E.; Khosla, Chaitan

    2016-01-01

    Ketoreductases (KRs) are the most widespread tailoring domains found in individual modules of assembly line polyketide synthases (PKSs), and are responsible for controlling the configurations of both the α-methyl and β-hydroxyl stereogenic centers in the growing polyketide chain. Because they recognize substrates that are covalently bound to acyl carrier proteins (ACPs) within the same PKS module, we sought to quantify the extent to which protein-protein recognition contributes to the turnover of these oxidoreductive enzymes using stand-alone domains from the 6-deoxyerythronolide B synthase (DEBS). Reduced 2-methyl-3-hydroxyacyl-ACP substrates derived from two enantiomeric acyl chains and four distinct ACP domains were synthesized and presented to four distinct KR domains. Two KRs, from DEBS modules 2 and 5, displayed little preference for oxidation of substrates tethered to their cognate ACP domains over those attached to the other ACP domains tested. In contrast, the KR from DEBS module 1 showed a ca. 10-50-fold preference for substrate attached to its native ACP domain, whereas the KR from DEBS module 6 actually displayed a ca. 10-fold preference for the ACP from DEBS module 5. Our findings suggest that recognition of the ACP by a KR domain is unlikely to affect the rate of native assembly line polyketide biosynthesis. In some cases, however, unfavorable KR-ACP interactions may suppress the rate of substrate processing when KR domains are swapped to construct hybrid PKS modules. PMID:27118242

  4. Transfer Learning for Activity Recognition: A Survey

    PubMed Central

    Cook, Diane; Feuz, Kyle D.; Krishnan, Narayanan C.

    2013-01-01

    Many intelligent systems that focus on the needs of a human require information about the activities being performed by the human. At the core of this capability is activity recognition, which is a challenging and well-researched problem. Activity recognition algorithms require substantial amounts of labeled training data yet need to perform well under very diverse circumstances. As a result, researchers have been designing methods to identify and utilize subtle connections between activity recognition datasets, or to perform transfer-based activity recognition. In this paper we survey the literature to highlight recent advances in transfer learning for activity recognition. We characterize existing approaches to transfer-based activity recognition by sensor modality, by differences between source and target environments, by data availability, and by type of information that is transferred. Finally, we present some grand challenges for the community to consider as this field is further developed. PMID:24039326

  5. Cascaded automatic target recognition (Cascaded ATR)

    NASA Astrophysics Data System (ADS)

    Walls, Bradley

    2010-04-01

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

  6. A conserved motif in the linker domain of STAT1 transcription factor is required for both recognition and release from high-affinity DNA-binding sites.

    PubMed

    Hüntelmann, Bettina; Staab, Julia; Herrmann-Lingen, Christoph; Meyer, Thomas

    2014-01-01

    Binding to specific palindromic sequences termed gamma-activated sites (GAS) is a hallmark of gene activation by members of the STAT (signal transducer and activator of transcription) family of cytokine-inducible transcription factors. However, the precise molecular mechanisms involved in the signal-dependent finding of target genes by STAT dimers have not yet been very well studied. In this study, we have characterized a sequence motif in the STAT1 linker domain which is highly conserved among the seven human STAT proteins and includes surface-exposed residues in close proximity to the bound DNA. Using site-directed mutagenesis, we have demonstrated that a lysine residue in position 567 of the full-length molecule is required for GAS recognition. The substitution of alanine for this residue completely abolished both binding to high-affinity GAS elements and transcriptional activation of endogenous target genes in cells stimulated with interferon-γ (IFNγ), while the time course of transient nuclear accumulation and tyrosine phosphorylation were virtually unchanged. In contrast, two glutamic acid residues (E559 and E563) on each monomer are important for the dissociation of dimeric STAT1 from DNA and, when mutated to alanine, result in elevated levels of tyrosine-phosphorylated STAT1 as well as prolonged IFNγ-stimulated nuclear accumulation. In conclusion, our data indicate that the kinetics of signal-dependent GAS binding is determined by an array of glutamic acid residues located at the interior surface of the STAT1 dimer. These negatively charged residues appear to align the long axis of the STAT1 dimer in a position perpendicular to the DNA, thereby facilitating the interaction between lysine 567 and the phosphodiester backbone of a bound GAS element, which is a prerequisite for transient gene induction.

  7. Line-based logo recognition through a web-camera

    NASA Astrophysics Data System (ADS)

    Chen, Xiaolu; Wang, Yangsheng; Feng, Xuetao

    2007-11-01

    Logo recognition has gained much development in the document retrieval and shape analysis domain. As human computer interaction becomes more and more popular, the logo recognition through a web-camera is a promising technology in view of application. But for practical application, the study of logo recognition in real scene is much more difficult than the work in clear scene. To cope with the need, we make some improvements on conventional method. First, moment information is used to calculate the test image's orientation angle, which is used to normalize the test image. Second, the main structure of the test image, which is represented by lines patterns, is acquired and modified Hausdorff distance is employed to match the image and each of the existing templates. The proposed method, which is invariant to scale and rotation, gives good result and can work at real-time. The main contribution of this paper is that some improvements are introduced into the exiting recognition framework which performs much better than the original one. Besides, we have built a highly successful logo recognition system using our improved method.

  8. Cas13d Is a Compact RNA-Targeting Type VI CRISPR Effector Positively Modulated by a WYL-Domain-Containing Accessory Protein.

    PubMed

    Yan, Winston X; Chong, Shaorong; Zhang, Huaibin; Makarova, Kira S; Koonin, Eugene V; Cheng, David R; Scott, David A

    2018-04-19

    Bacterial class 2 CRISPR-Cas systems utilize a single RNA-guided protein effector to mitigate viral infection. We aggregated genomic data from multiple sources and constructed an expanded database of predicted class 2 CRISPR-Cas systems. A search for novel RNA-targeting systems identified subtype VI-D, encoding dual HEPN domain-containing Cas13d effectors and putative WYL-domain-containing accessory proteins (WYL1 and WYL-b1 through WYL-b5). The median size of Cas13d proteins is 190 to 300 aa smaller than that of Cas13a-Cas13c. Despite their small size, Cas13d orthologs from Eubacterium siraeum (Es) and Ruminococcus sp. (Rsp) are active in both CRISPR RNA processing and targeting, as well as collateral RNA cleavage, with no target-flanking sequence requirements. The RspWYL1 protein stimulates RNA cleavage by both EsCas13d and RspCas13d, demonstrating a common regulatory mechanism for divergent Cas13d orthologs. The small size, minimal targeting constraints, and modular regulation of Cas13d effectors further expands the CRISPR toolkit for RNA manipulation and detection. Copyright © 2018 Elsevier Inc. All rights reserved.

  9. Crystal structure and novel recognition motif of rho ADP-ribosylating C3 exoenzyme from Clostridium botulinum: structural insights for recognition specificity and catalysis.

    PubMed

    Han, S; Arvai, A S; Clancy, S B; Tainer, J A

    2001-01-05

    Clostridium botulinum C3 exoenzyme inactivates the small GTP-binding protein family Rho by ADP-ribosylating asparagine 41, which depolymerizes the actin cytoskeleton. C3 thus represents a major family of the bacterial toxins that transfer the ADP-ribose moiety of NAD to specific amino acids in acceptor proteins to modify key biological activities in eukaryotic cells, including protein synthesis, differentiation, transformation, and intracellular signaling. The 1.7 A resolution C3 exoenzyme structure establishes the conserved features of the core NAD-binding beta-sandwich fold with other ADP-ribosylating toxins despite little sequence conservation. Importantly, the central core of the C3 exoenzyme structure is distinguished by the absence of an active site loop observed in many other ADP-ribosylating toxins. Unlike the ADP-ribosylating toxins that possess the active site loop near the central core, the C3 exoenzyme replaces the active site loop with an alpha-helix, alpha3. Moreover, structural and sequence similarities with the catalytic domain of vegetative insecticidal protein 2 (VIP2), an actin ADP-ribosyltransferase, unexpectedly implicates two adjacent, protruding turns, which join beta5 and beta6 of the toxin core fold, as a novel recognition specificity motif for this newly defined toxin family. Turn 1 evidently positions the solvent-exposed, aromatic side-chain of Phe209 to interact with the hydrophobic region of Rho adjacent to its GTP-binding site. Turn 2 evidently both places the Gln212 side-chain for hydrogen bonding to recognize Rho Asn41 for nucleophilic attack on the anomeric carbon of NAD ribose and holds the key Glu214 catalytic side-chain in the adjacent catalytic pocket. This proposed bipartite ADP-ribosylating toxin turn-turn (ARTT) motif places the VIP2 and C3 toxin classes into a single ARTT family characterized by analogous target protein recognition via turn 1 aromatic and turn 2 hydrogen-bonding side-chain moieties. Turn 2 centrally anchors

  10. Kinase domain-targeted isolation of defense-related receptor-like kinases (RLK/Pelle) in Platanus×acerifolia: phylogenetic and structural analysis.

    PubMed

    Pilotti, Massimo; Brunetti, Angela; Uva, Paolo; Lumia, Valentina; Tizzani, Lorenza; Gervasi, Fabio; Iacono, Michele; Pindo, Massimo

    2014-12-08

    Plant receptor-like kinase (RLK/Pelle) family regulates growth and developmental processes and interaction with pathogens and symbionts.Platanaceae is one of the earliest branches of Eudicots temporally located before the split which gave rise to Rosids and Asterids. Thus investigations into the RLK family in Platanus can provide information on the evolution of this gene family in the land plants.Moreover RLKs are good candidates for finding genes that are able to confer resistance to Platanus pathogens. Degenerate oligonucleotide primers targeting the kinase domain of stress-related RLKs were used to isolate for the first time 111 RLK gene fragments in Platanus×acerifolia. Sequences were classified as candidates of the following subfamilies: CrRLK1L, LRR XII, WAK-like, and LRR X-BRI1 group. All the structural features typical of the RLK kinase domain were identified, including the non-RD motif which marks potential pathogen recognition receptors (PRRs). The LRR XII candidates, whose counterpart in Arabidopsis and rice comprises non-RD PRRs, were mostly non-RD kinases, suggesting a group of PRRs. Region-specific signatures of a relaxed purifying selection in the LRR XII candidates were also found, which is novel for plant RLK kinase domain and further supports the role of LRR XII candidates as PRRs. As we obtained CrRLK1L candidates using primers designed on Pto of tomato, we analysed the phylogenetic relationship between CrRLK1L and Pto-like of plant species. We thus classified all non-solanaceous Pto-like genes as CrRLK1L and highlighted for the first time the close phylogenetic vicinity between CrRLK1L and Pto group. The origins of Pto from CrRLK1L is proposed as an evolutionary mechanism. The signatures of relaxed purifying selection highlight that a group of RLKs might have been involved in the expression of phenotypic plasticity and is thus a good candidate for investigations into pathogen resistance.Search of Pto-like genes in Platanus highlighted the close

  11. Creation of a type IIS restriction endonuclease with a long recognition sequence

    PubMed Central

    Lippow, Shaun M.; Aha, Patti M.; Parker, Matthew H.; Blake, William J.; Baynes, Brian M.; Lipovšek, Daša

    2009-01-01

    Type IIS restriction endonucleases cleave DNA outside their recognition sequences, and are therefore particularly useful in the assembly of DNA from smaller fragments. A limitation of type IIS restriction endonucleases in assembly of long DNA sequences is the relative abundance of their target sites. To facilitate ligation-based assembly of extremely long pieces of DNA, we have engineered a new type IIS restriction endonuclease that combines the specificity of the homing endonuclease I-SceI with the type IIS cleavage pattern of FokI. We linked a non-cleaving mutant of I-SceI, which conveys to the chimeric enzyme its specificity for an 18-bp DNA sequence, to the catalytic domain of FokI, which cuts DNA at a defined site outside the target site. Whereas previously described chimeric endonucleases do not produce type IIS-like precise DNA overhangs suitable for ligation, our chimeric endonuclease cleaves double-stranded DNA exactly 2 and 6 nt from the target site to generate homogeneous, 5′, four-base overhangs, which can be ligated with 90% fidelity. We anticipate that these enzymes will be particularly useful in manipulation of DNA fragments larger than a thousand bases, which are very likely to contain target sites for all natural type IIS restriction endonucleases. PMID:19304757

  12. Repurposing anticancer drugs for targeting necroptosis.

    PubMed

    Fulda, Simone

    2018-04-25

    Necroptosis represents a form of programmed cell death that can be engaged by various upstream signals, for example by ligation of death receptors, by viral sensors or by pattern recognition receptors. It depends on several key signaling proteins, including the kinases Receptor-Interacting Protein (RIP)1 and RIP3 and the pseudokinase mixed-lineage kinase domain-like protein (MLKL). Necroptosis has been implicated in a number of physiological and pathophysiological conditions and is disturbed in many human diseases. Thus, targeted interference with necroptosis signaling may offer new opportunities for the treatment of human diseases. Besides structure-based drug design, in recent years drug repositioning has emerged as a promising alternative to develop drug-like compounds. There is accumulating evidence showing that multi-targeting kinase inhibitors, for example Dabrafenib, Vemurafenib, Sorafenib, Pazopanib and Ponatinib, used for the treatment of cancer also display anti-necroptotic activity. This review summarizes recent evidence indicating that some anticancer kinase inhibitors also negatively affect necroptosis signaling. This implies that some cancer therapeutics may be repurposed for other pathologies, e.g. ischemic or inflammatory diseases.

  13. Lexical leverage: Category knowledge boosts real-time novel word recognition in two-year- olds

    PubMed Central

    Borovsky, Arielle; Ellis, Erica M.; Evans, Julia L.; Elman, Jeffrey L.

    2016-01-01

    Recent research suggests that infants tend to add words to their vocabulary that are semantically related to other known words, though it is not clear why this pattern emerges. In this paper, we explore whether infants to leverage their existing vocabulary and semantic knowledge when interpreting novel label-object mappings in real-time. We initially identified categorical domains for which individual 24-month-old infants have relatively higher and lower levels of knowledge, irrespective of overall vocabulary size. Next, we taught infants novel words in these higher and lower knowledge domains and then asked if their subsequent real-time recognition of these items varied as a function of their category knowledge. While our participants successfully acquired the novel label -object mappings in our task, there were important differences in the way infants recognized these words in real time. Namely, infants showed more robust recognition of high (vs. low) domain knowledge words. These findings suggest that dense semantic structure facilitates early word learning and real-time novel word recognition. PMID:26452444

  14. The human RNA-binding protein and E3 ligase MEX-3C binds the MEX-3-recognition element (MRE) motif with high affinity.

    PubMed

    Yang, Lingna; Wang, Chongyuan; Li, Fudong; Zhang, Jiahai; Nayab, Anam; Wu, Jihui; Shi, Yunyu; Gong, Qingguo

    2017-09-29

    MEX-3 is a K-homology (KH) domain-containing RNA-binding protein first identified as a translational repressor in Caenorhabditis elegans , and its four orthologs (MEX-3A-D) in human and mouse were subsequently found to have E3 ubiquitin ligase activity mediated by a RING domain and critical for RNA degradation. Current evidence implicates human MEX-3C in many essential biological processes and suggests a strong connection with immune diseases and carcinogenesis. The highly conserved dual KH domains in MEX-3 proteins enable RNA binding and are essential for the recognition of the 3'-UTR and post-transcriptional regulation of MEX-3 target transcripts. However, the molecular mechanisms of translational repression and the consensus RNA sequence recognized by the MEX-3C KH domain are unknown. Here, using X-ray crystallography and isothermal titration calorimetry, we investigated the RNA-binding activity and selectivity of human MEX-3C dual KH domains. Our high-resolution crystal structures of individual KH domains complexed with a noncanonical U-rich and a GA-rich RNA sequence revealed that the KH1/2 domains of human MEX-3C bound MRE10, a 10-mer RNA (5'-CAGAGUUUAG-3') consisting of an eight-nucleotide MEX-3-recognition element (MRE) motif, with high affinity. Of note, we also identified a consensus RNA motif recognized by human MEX-3C. The potential RNA-binding sites in the 3'-UTR of the human leukocyte antigen serotype ( HLA-A2 ) mRNA were mapped with this RNA-binding motif and further confirmed by fluorescence polarization. The binding motif identified here will provide valuable information for future investigations of the functional pathways controlled by human MEX-3C and for predicting potential mRNAs regulated by this enzyme. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  15. Continued effects of context reinstatement in recognition.

    PubMed

    Hanczakowski, Maciej; Zawadzka, Katarzyna; Macken, Bill

    2015-07-01

    The context reinstatement effect refers to the enhanced memory performance found when the context information paired with a target item at study is re-presented at test. Here we investigated the consequences of the way that context information is processed in such a setting that gives rise to its beneficial effect on item recognition memory. Specifically, we assessed whether reinstating context in a recognition test facilitates subsequent memory for this context, beyond the facilitation conferred by presentation of the same context with a different study item. Reinstating the study context at test led to better accuracy in two-alternative forced choice recognition for target faces than did re-pairing those faces with another context encountered during the study phase. The advantage for reinstated over re-paired conditions occurred for both within-subjects (Exp. 1) and between-subjects (Exp. 2) manipulations. Critically, in a subsequent recognition test for the contexts themselves, contexts that had previously served in the reinstated condition were recognized better than contexts that had previously served in the re-paired context condition. This constitutes the first demonstration of continuous effects of context reinstatement on memory for context.

  16. Redirecting Specificity of T cells Using the Sleeping Beauty System to Express Chimeric Antigen Receptors by Mix-and-Matching of VL and VH Domains Targeting CD123+ Tumors.

    PubMed

    Thokala, Radhika; Olivares, Simon; Mi, Tiejuan; Maiti, Sourindra; Deniger, Drew; Huls, Helen; Torikai, Hiroki; Singh, Harjeet; Champlin, Richard E; Laskowski, Tamara; McNamara, George; Cooper, Laurence J N

    2016-01-01

    Adoptive immunotherapy infusing T cells with engineered specificity for CD19 expressed on B- cell malignancies is generating enthusiasm to extend this approach to other hematological malignancies, such as acute myelogenous leukemia (AML). CD123, or interleukin 3 receptor alpha, is overexpressed on most AML and some lymphoid malignancies, such as acute lymphocytic leukemia (ALL), and has been an effective target for T cells expressing chimeric antigen receptors (CARs). The prototypical CAR encodes a VH and VL from one monoclonal antibody (mAb), coupled to a transmembrane domain and one or more cytoplasmic signaling domains. Previous studies showed that treatment of an experimental AML model with CD123-specific CAR T cells was therapeutic, but at the cost of impaired myelopoiesis, highlighting the need for systems to define the antigen threshold for CAR recognition. Here, we show that CARs can be engineered using VH and VL chains derived from different CD123-specific mAbs to generate a panel of CAR+ T cells. While all CARs exhibited specificity to CD123, one VH and VL combination had reduced lysis of normal hematopoietic stem cells. This CAR's in vivo anti-tumor activity was similar whether signaling occurred via chimeric CD28 or CD137, prolonging survival in both AML and ALL models. Co-expression of inducible caspase 9 eliminated CAR+ T cells. These data help support the use of CD123-specific CARs for treatment of CD123+ hematologic malignancies.

  17. Mapping small molecule binding data to structural domains

    PubMed Central

    2012-01-01

    Background Large-scale bioactivity/SAR Open Data has recently become available, and this has allowed new analyses and approaches to be developed to help address the productivity and translational gaps of current drug discovery. One of the current limitations of these data is the relative sparsity of reported interactions per protein target, and complexities in establishing clear relationships between bioactivity and targets using bioinformatics tools. We detail in this paper the indexing of targets by the structural domains that bind (or are likely to bind) the ligand within a full-length protein. Specifically, we present a simple heuristic to map small molecule binding to Pfam domains. This profiling can be applied to all proteins within a genome to give some indications of the potential pharmacological modulation and regulation of all proteins. Results In this implementation of our heuristic, ligand binding to protein targets from the ChEMBL database was mapped to structural domains as defined by profiles contained within the Pfam-A database. Our mapping suggests that the majority of assay targets within the current version of the ChEMBL database bind ligands through a small number of highly prevalent domains, and conversely the majority of Pfam domains sampled by our data play no currently established role in ligand binding. Validation studies, carried out firstly against Uniprot entries with expert binding-site annotation and secondly against entries in the wwPDB repository of crystallographic protein structures, demonstrate that our simple heuristic maps ligand binding to the correct domain in about 90 percent of all assessed cases. Using the mappings obtained with our heuristic, we have assembled ligand sets associated with each Pfam domain. Conclusions Small molecule binding has been mapped to Pfam-A domains of protein targets in the ChEMBL bioactivity database. The result of this mapping is an enriched annotation of small molecule bioactivity data and a

  18. An insight to the dynamics of conserved water molecular triad in IMPDH II (human): recognition of cofactor and substrate to catalytic Arg 322.

    PubMed

    Bairagya, Hridoy R; Mukhopadhyay, Bishnu P; Sekar, K

    2009-10-01

    Inosine 5' monophosphate dehydrogenase (IMPDH II) is a key enzyme involved in the de novo biosynthesis pathway of purine nucleotides and is also considered to be an excellent target for cancer inhibitor design. The conserve R 322 residue (in human) is thought to play some role in the recognition of inhibitor and cofactor through the catalytic D 364 and N 303. The 15 ns simulation and the water dynamics of the three different PDB structures (1B3O, 1NF7, and 1NFB) of human IMPDH by CHARMM force field have clearly indicated the involvement of three conserved water molecules (W(L), W(M), and W(C)) in the recognition of catalytic residues (R 322, D 364, and N 303) to inhibitor and cofactor. Both the guanidine nitrogen atoms (NH1 and NH 2) of the R 322 have anchored the di- and mono-nucleotide (cofactor and inhibitor) binding domains via the conserved W(C) and W(L) water molecules. Another conserved water molecule WM seems to bridge the two domains including the R 322 and also the W(C) and W(L) through seven centers H-bonding coordination. The conserved water molecular triad (W(C)-W(M)-W(L)) in the protein complex may thought to play some important role in the recognition of inhibitor and cofactor to the protein through R 322 residue.

  19. Resilient memory for melodies: The number of intervening melodies does not influence novel melody recognition.

    PubMed

    Herff, Steffen A; Olsen, Kirk N; Dean, Roger T

    2018-05-01

    In many memory domains, a decrease in recognition performance between the first and second presentation of an object is observed as the number of intervening items increases. However, this effect is not universal. Within the auditory domain, this form of interference has been demonstrated in word and single-note recognition, but has yet to be substantiated using relatively complex musical material such as a melody. Indeed, it is becoming clear that music shows intriguing properties when it comes to memory. This study investigated how the number of intervening items influences memory for melodies. In Experiments 1, 2 and 3, one melody was presented per trial in a continuous recognition paradigm. After each melody, participants indicated whether they had heard the melody in the experiment before by responding "old" or "new." In Experiment 4, participants rated perceived familiarity for every melody without being told that melodies reoccur. In four experiments using two corpora of music, two different memory tasks, transposed and untransposed melodies and up to 195 intervening melodies, no sign of a disruptive effect from the number of intervening melodies beyond the first was observed. We propose a new "regenerative multiple representations" conjecture to explain why intervening items increase interference in recognition memory for most domains but not music. This conjecture makes several testable predictions and has the potential to strengthen our understanding of domain specificity in human memory, while moving one step closer to explaining the "paradox" that is memory for melody.

  20. PHYSICAL MODEL FOR RECOGNITION TUNNELING

    PubMed Central

    Krstić, Predrag; Ashcroft, Brian; Lindsay, Stuart

    2015-01-01

    Recognition tunneling (RT) identifies target molecules trapped between tunneling electrodes functionalized with recognition molecules that serve as specific chemical linkages between the metal electrodes and the trapped target molecule. Possible applications include single molecule DNA and protein sequencing. This paper addresses several fundamental aspects of RT by multiscale theory, applying both all-atom and coarse-grained DNA models: (1) We show that the magnitude of the observed currents are consistent with the results of non-equilibrium Green's function calculations carried out on a solvated all-atom model. (2) Brownian fluctuations in hydrogen bond-lengths lead to current spikes that are similar to what is observed experimentally. (3) The frequency characteristics of these fluctuations can be used to identify the trapped molecules with a machine-learning algorithm, giving a theoretical underpinning to this new method of identifying single molecule signals. PMID:25650375