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Sample records for based auto-contoured target

  1. PET-CT-Based Auto-Contouring in Non-Small-Cell Lung Cancer Correlates With Pathology and Reduces Interobserver Variability in the Delineation of the Primary Tumor and Involved Nodal Volumes

    International Nuclear Information System (INIS)

    Baardwijk, Angela van; Bosmans, Geert; Boersma, Liesbeth; Buijsen, Jeroen; Wanders, Stofferinus; Hochstenbag, Monique; Suylen, Robert-Jan van; Dekker, Andre; Dehing-Oberije, Cary; Houben, Ruud; Bentzen, Soren M.; Kroonenburgh, Marinus van; Lambin, Philippe; Ruysscher, Dirk de

    2007-01-01

    Purpose: To compare source-to-background ratio (SBR)-based PET-CT auto-delineation with pathology in non-small-cell lung cancer (NSCLC) and to investigate whether auto-delineation reduces the interobserver variability compared with manual PET-CT-based gross tumor volume (GTV) delineation. Methods and Materials: Source-to-background ratio-based auto-delineation was compared with macroscopic tumor dimensions to assess its validity in 23 tumors. Thereafter, GTVs were delineated manually on 33 PET-CT scans by five observers for the primary tumor (GTV-1) and the involved lymph nodes (GTV-2). The delineation was repeated after 6 months with the auto-contour provided. This contour was edited by the observers. For comparison, the concordance index (CI) was calculated, defined as the ratio of intersection and the union of two volumes (A intersection B)/(A union B). Results: The maximal tumor diameter of the SBR-based auto-contour correlated strongly with the macroscopic diameter of primary tumors (correlation coefficient = 0.90) and was shown to be accurate for involved lymph nodes (sensitivity 67%, specificity 95%). The median auto-contour-based target volumes were smaller than those defined by manual delineation for GTV-1 (31.8 and 34.6 cm 3 , respectively; p = 0.001) and GTV-2 (16.3 and 21.8 cm 3 , respectively; p 0.02). The auto-contour-based method showed higher CIs than the manual method for GTV-1 (0.74 and 0.70 cm 3 , respectively; p 3 , respectively; p = 0.11). Conclusion: Source-to-background ratio-based auto-delineation showed a good correlation with pathology, decreased the delineated volumes of the GTVs, and reduced the interobserver variability. Auto-contouring may further improve the quality of target delineation in NSCLC patients

  2. WE-G-BRD-07: Automated MR Image Standardization and Auto-Contouring Strategy for MRI-Based Adaptive Brachytherapy for Cervix Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Saleh, H Al; Erickson, B; Paulson, E [Medical College of Wisconsin, Milwaukee, WI (United States)

    2015-06-15

    Purpose: MRI-based adaptive brachytherapy (ABT) is an emerging treatment modality for patients with gynecological tumors. However, MR image intensity non-uniformities (IINU) can vary from fraction to fraction, complicating image interpretation and auto-contouring accuracy. We demonstrate here an automated MR image standardization and auto-contouring strategy for MRI-based ABT of cervix cancer. Methods: MR image standardization consisted of: 1) IINU correction using the MNI N3 algorithm, 2) noise filtering using anisotropic diffusion, and 3) signal intensity normalization using the volumetric median. This post-processing chain was implemented as a series of custom Matlab and Java extensions in MIM (v6.4.5, MIM Software) and was applied to 3D T2 SPACE images of six patients undergoing MRI-based ABT at 3T. Coefficients of variation (CV=σ/µ) were calculated for both original and standardized images and compared using Mann-Whitney tests. Patient-specific cumulative MR atlases of bladder, rectum, and sigmoid contours were constructed throughout ABT, using original and standardized MR images from all previous ABT fractions. Auto-contouring was performed in MIM two ways: 1) best-match of one atlas image to the daily MR image, 2) multi-match of all previous fraction atlas images to the daily MR image. Dice’s Similarity Coefficients (DSCs) were calculated for auto-generated contours relative to reference contours for both original and standardized MR images and compared using Mann-Whitney tests. Results: Significant improvements in CV were detected following MR image standardization (p=0.0043), demonstrating an improvement in MR image uniformity. DSCs consistently increased for auto-contoured bladder, rectum, and sigmoid following MR image standardization, with the highest DSCs detected when the combination of MR image standardization and multi-match cumulative atlas-based auto-contouring was utilized. Conclusion: MR image standardization significantly improves MR image

  3. WE-G-BRD-07: Automated MR Image Standardization and Auto-Contouring Strategy for MRI-Based Adaptive Brachytherapy for Cervix Cancer

    International Nuclear Information System (INIS)

    Saleh, H Al; Erickson, B; Paulson, E

    2015-01-01

    Purpose: MRI-based adaptive brachytherapy (ABT) is an emerging treatment modality for patients with gynecological tumors. However, MR image intensity non-uniformities (IINU) can vary from fraction to fraction, complicating image interpretation and auto-contouring accuracy. We demonstrate here an automated MR image standardization and auto-contouring strategy for MRI-based ABT of cervix cancer. Methods: MR image standardization consisted of: 1) IINU correction using the MNI N3 algorithm, 2) noise filtering using anisotropic diffusion, and 3) signal intensity normalization using the volumetric median. This post-processing chain was implemented as a series of custom Matlab and Java extensions in MIM (v6.4.5, MIM Software) and was applied to 3D T2 SPACE images of six patients undergoing MRI-based ABT at 3T. Coefficients of variation (CV=σ/µ) were calculated for both original and standardized images and compared using Mann-Whitney tests. Patient-specific cumulative MR atlases of bladder, rectum, and sigmoid contours were constructed throughout ABT, using original and standardized MR images from all previous ABT fractions. Auto-contouring was performed in MIM two ways: 1) best-match of one atlas image to the daily MR image, 2) multi-match of all previous fraction atlas images to the daily MR image. Dice’s Similarity Coefficients (DSCs) were calculated for auto-generated contours relative to reference contours for both original and standardized MR images and compared using Mann-Whitney tests. Results: Significant improvements in CV were detected following MR image standardization (p=0.0043), demonstrating an improvement in MR image uniformity. DSCs consistently increased for auto-contoured bladder, rectum, and sigmoid following MR image standardization, with the highest DSCs detected when the combination of MR image standardization and multi-match cumulative atlas-based auto-contouring was utilized. Conclusion: MR image standardization significantly improves MR image

  4. TU-AB-202-10: How Effective Are Current Atlas Selection Methods for Atlas-Based Auto-Contouring in Radiotherapy Planning?

    Energy Technology Data Exchange (ETDEWEB)

    Peressutti, D; Schipaanboord, B; Kadir, T; Gooding, M [Mirada Medical Limited, Science and Medical Technology, Oxford (United Kingdom); Soest, J van; Lustberg, T; Elmpt, W van; Dekker, A [Maastricht University Medical Centre, Department of Radiation Oncology MAASTRO - GROW School for Oncology Developmental Biology, Maastricht (Netherlands)

    2016-06-15

    Purpose: To investigate the effectiveness of atlas selection methods for improving atlas-based auto-contouring in radiotherapy planning. Methods: 275 H&N clinically delineated cases were employed as an atlas database from which atlases would be selected. A further 40 previously contoured cases were used as test patients against which atlas selection could be performed and evaluated. 26 variations of selection methods proposed in the literature and used in commercial systems were investigated. Atlas selection methods comprised either global or local image similarity measures, computed after rigid or deformable registration, combined with direct atlas search or with an intermediate template image. Workflow Box (Mirada-Medical, Oxford, UK) was used for all auto-contouring. Results on brain, brainstem, parotids and spinal cord were compared to random selection, a fixed set of 10 “good” atlases, and optimal selection by an “oracle” with knowledge of the ground truth. The Dice score and the average ranking with respect to the “oracle” were employed to assess the performance of the top 10 atlases selected by each method. Results: The fixed set of “good” atlases outperformed all of the atlas-patient image similarity-based selection methods (mean Dice 0.715 c.f. 0.603 to 0.677). In general, methods based on exhaustive comparison of local similarity measures showed better average Dice scores (0.658 to 0.677) compared to the use of either template image (0.655 to 0.672) or global similarity measures (0.603 to 0.666). The performance of image-based selection methods was found to be only slightly better than a random (0.645). Dice scores given relate to the left parotid, but similar results patterns were observed for all organs. Conclusion: Intuitively, atlas selection based on the patient CT is expected to improve auto-contouring performance. However, it was found that published approaches performed marginally better than random and use of a fixed set of

  5. SU-C-BRB-05: Determining the Adequacy of Auto-Contouring Via Probabilistic Assessment of Ensuing Treatment Plan Metrics in Comparison with Manual Contours

    International Nuclear Information System (INIS)

    Nourzadeh, H; Watkins, W; Siebers, J; Ahmad, M

    2016-01-01

    Purpose: To determine if auto-contour and manual-contour—based plans differ when evaluated with respect to probabilistic coverage metrics and biological model endpoints for prostate IMRT. Methods: Manual and auto-contours were created for 149 CT image sets acquired from 16 unique prostate patients. A single physician manually contoured all images. Auto-contouring was completed utilizing Pinnacle’s Smart Probabilistic Image Contouring Engine (SPICE). For each CT, three different 78 Gy/39 fraction 7-beam IMRT plans are created; PD with drawn ROIs, PAS with auto-contoured ROIs, and PM with auto-contoured OARs with the manually drawn target. For each plan, 1000 virtual treatment simulations with different sampled systematic errors for each simulation and a different sampled random error for each fraction were performed using our in-house GPU-accelerated robustness analyzer tool which reports the statistical probability of achieving dose-volume metrics, NTCP, TCP, and the probability of achieving the optimization criteria for both auto-contoured (AS) and manually drawn (D) ROIs. Metrics are reported for all possible cross-evaluation pairs of ROI types (AS,D) and planning scenarios (PD,PAS,PM). Bhattacharyya coefficient (BC) is calculated to measure the PDF similarities for the dose-volume metric, NTCP, TCP, and objectives with respect to the manually drawn contour evaluated on base plan (D-PD). Results: We observe high BC values (BC≥0.94) for all OAR objectives. BC values of max dose objective on CTV also signify high resemblance (BC≥0.93) between the distributions. On the other hand, BC values for CTV’s D95 and Dmin objectives are small for AS-PM, AS-PD. NTCP distributions are similar across all evaluation pairs, while TCP distributions of AS-PM, AS-PD sustain variations up to %6 compared to other evaluated pairs. Conclusion: No significant probabilistic differences are observed in the metrics when auto-contoured OARs are used. The prostate auto-contour needs

  6. Does atlas-based autosegmentation of neck levels require subsequent manual contour editing to avoid risk of severe target underdosage? A dosimetric analysis

    International Nuclear Information System (INIS)

    Voet, Peter W.J.; Dirkx, Maarten L.P.; Teguh, David N.; Hoogeman, Mischa S.; Levendag, Peter C.; Heijmen, Ben J.M.

    2011-01-01

    Background and purpose: To investigate the dosimetric impact of not editing auto-contours of the elective neck and organs at risk (OAR), generated with atlas-based autosegmentation (ABAS) (Elekta software) for head and neck cancer patients. Materials and methods: For nine patients ABAS auto-contours and auto-contours edited by two observers were available. Based on the non-edited auto-contours clinically acceptable IMRT plans were constructed (designated 'ABAS plans'). These plans were then evaluated for the two edited structure sets, by quantifying the percentage of the neck-PTV receiving more than 95% of the prescribed dose (V 95 ) and the near-minimum dose (D 99 ) in the neck PTV. Dice coefficients and mean contour distances were calculated to quantify the similarity of ABAS auto-contours with the structure sets edited by observer 1 and observer 2. To study the dosimetric importance of editing OAR auto-contours a new IMRT plan was generated for each patient-observer combination, based on the observer's edited CTV and the non-edited salivary gland auto-contours. For each plan mean doses for the non-edited glands were compared with doses for the same glands edited by the observer. Results: For both observers, edited neck CTVs were larger than ABAS auto-contours (p ≤ 0.04), by a mean of 8.7%. When evaluating ABAS plans on the PTVs of the edited structure sets, V 95 reduced by 7.2% ± 5.4% (1 SD) (p 99 was 14.2 Gy (range 1-54 Gy). Even for Dice coefficients >0.8 and mean contour distances 99 up to 11 Gy were observed. For treatment plans based on observer PTVs and non-edited auto-contoured salivary glands, the mean doses in the edited glands differed by only -0.6 Gy ± 1.0 Gy (p = 0.06). Conclusions: Editing of auto-contoured neck CTVs generated by ABAS is required to avoid large underdosages in target volumes. Often used similarity measures for evaluation of auto-contouring algorithms, such as dice coefficients, do not predict well for expected PTV underdose

  7. Tumour auto-contouring on 2d cine MRI for locally advanced lung cancer: A comparative study.

    Science.gov (United States)

    Fast, Martin F; Eiben, Björn; Menten, Martin J; Wetscherek, Andreas; Hawkes, David J; McClelland, Jamie R; Oelfke, Uwe

    2017-12-01

    Radiotherapy guidance based on magnetic resonance imaging (MRI) is currently becoming a clinical reality. Fast 2d cine MRI sequences are expected to increase the precision of radiation delivery by facilitating tumour delineation during treatment. This study compares four auto-contouring algorithms for the task of delineating the primary tumour in six locally advanced (LA) lung cancer patients. Twenty-two cine MRI sequences were acquired using either a balanced steady-state free precession or a spoiled gradient echo imaging technique. Contours derived by the auto-contouring algorithms were compared against manual reference contours. A selection of eight image data sets was also used to assess the inter-observer delineation uncertainty. Algorithmically derived contours agreed well with the manual reference contours (median Dice similarity index: ⩾0.91). Multi-template matching and deformable image registration performed significantly better than feature-driven registration and the pulse-coupled neural network (PCNN). Neither MRI sequence nor image orientation was a conclusive predictor for algorithmic performance. Motion significantly degraded the performance of the PCNN. The inter-observer variability was of the same order of magnitude as the algorithmic performance. Auto-contouring of tumours on cine MRI is feasible in LA lung cancer patients. Despite large variations in implementation complexity, the different algorithms all have relatively similar performance. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  8. SU-C-BRA-05: Delineating High-Dose Clinical Target Volumes for Head and Neck Tumors Using Machine Learning Algorithms

    International Nuclear Information System (INIS)

    Cardenas, C; Wong, A; Mohamed, A; Fuller, C; Yang, J; Court, L; Aristophanous, M; Rao, A

    2016-01-01

    Purpose: To develop and test population-based machine learning algorithms for delineating high-dose clinical target volumes (CTVs) in H&N tumors. Automating and standardizing the contouring of CTVs can reduce both physician contouring time and inter-physician variability, which is one of the largest sources of uncertainty in H&N radiotherapy. Methods: Twenty-five node-negative patients treated with definitive radiotherapy were selected (6 right base of tongue, 11 left and 9 right tonsil). All patients had GTV and CTVs manually contoured by an experienced radiation oncologist prior to treatment. This contouring process, which is driven by anatomical, pathological, and patient specific information, typically results in non-uniform margin expansions about the GTV. Therefore, we tested two methods to delineate high-dose CTV given a manually-contoured GTV: (1) regression-support vector machines(SVM) and (2) classification-SVM. These models were trained and tested on each patient group using leave-one-out cross-validation. The volume difference(VD) and Dice similarity coefficient(DSC) between the manual and auto-contoured CTV were calculated to evaluate the results. Distances from GTV-to-CTV were computed about each patient’s GTV and these distances, in addition to distances from GTV to surrounding anatomy in the expansion direction, were utilized in the regression-SVM method. The classification-SVM method used categorical voxel-information (GTV, selected anatomical structures, else) from a 3×3×3cm3 ROI centered about the voxel to classify voxels as CTV. Results: Volumes for the auto-contoured CTVs ranged from 17.1 to 149.1cc and 17.4 to 151.9cc; the average(range) VD between manual and auto-contoured CTV were 0.93 (0.48–1.59) and 1.16(0.48–1.97); while average(range) DSC values were 0.75(0.59–0.88) and 0.74(0.59–0.81) for the regression-SVM and classification-SVM methods, respectively. Conclusion: We developed two novel machine learning methods to delineate

  9. SU-C-BRA-05: Delineating High-Dose Clinical Target Volumes for Head and Neck Tumors Using Machine Learning Algorithms

    Energy Technology Data Exchange (ETDEWEB)

    Cardenas, C [Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); The University of Texas Graduate School of Biomedical Sciences, Houston, TX (United States); Wong, A [Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); School of Medicine, The University of Texas Health Sciences Center at San Antonio, San Antonio, TX (United States); Mohamed, A; Fuller, C [Department of Radiation Oncology, The University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Yang, J; Court, L; Aristophanous, M [Department of Radiation Physics, The University of Texas M.D. Anderson Cancer Center, Houston, TX (United States); Rao, A [Department of Bioinformatics and Computational Biology, The University of Texas M.D. Anderson Cancer Center, Houston, TX (United States)

    2016-06-15

    Purpose: To develop and test population-based machine learning algorithms for delineating high-dose clinical target volumes (CTVs) in H&N tumors. Automating and standardizing the contouring of CTVs can reduce both physician contouring time and inter-physician variability, which is one of the largest sources of uncertainty in H&N radiotherapy. Methods: Twenty-five node-negative patients treated with definitive radiotherapy were selected (6 right base of tongue, 11 left and 9 right tonsil). All patients had GTV and CTVs manually contoured by an experienced radiation oncologist prior to treatment. This contouring process, which is driven by anatomical, pathological, and patient specific information, typically results in non-uniform margin expansions about the GTV. Therefore, we tested two methods to delineate high-dose CTV given a manually-contoured GTV: (1) regression-support vector machines(SVM) and (2) classification-SVM. These models were trained and tested on each patient group using leave-one-out cross-validation. The volume difference(VD) and Dice similarity coefficient(DSC) between the manual and auto-contoured CTV were calculated to evaluate the results. Distances from GTV-to-CTV were computed about each patient’s GTV and these distances, in addition to distances from GTV to surrounding anatomy in the expansion direction, were utilized in the regression-SVM method. The classification-SVM method used categorical voxel-information (GTV, selected anatomical structures, else) from a 3×3×3cm3 ROI centered about the voxel to classify voxels as CTV. Results: Volumes for the auto-contoured CTVs ranged from 17.1 to 149.1cc and 17.4 to 151.9cc; the average(range) VD between manual and auto-contoured CTV were 0.93 (0.48–1.59) and 1.16(0.48–1.97); while average(range) DSC values were 0.75(0.59–0.88) and 0.74(0.59–0.81) for the regression-SVM and classification-SVM methods, respectively. Conclusion: We developed two novel machine learning methods to delineate

  10. Comparison of Intensity-Modulated Radiotherapy Planning Based on Manual and Automatically Generated Contours Using Deformable Image Registration in Four-Dimensional Computed Tomography of Lung Cancer Patients

    International Nuclear Information System (INIS)

    Weiss, Elisabeth; Wijesooriya, Krishni; Ramakrishnan, Viswanathan; Keall, Paul J.

    2008-01-01

    Purpose: To evaluate the implications of differences between contours drawn manually and contours generated automatically by deformable image registration for four-dimensional (4D) treatment planning. Methods and Materials: In 12 lung cancer patients intensity-modulated radiotherapy (IMRT) planning was performed for both manual contours and automatically generated ('auto') contours in mid and peak expiration of 4D computed tomography scans, with the manual contours in peak inspiration serving as the reference for the displacement vector fields. Manual and auto plans were analyzed with respect to their coverage of the manual contours, which were assumed to represent the anatomically correct volumes. Results: Auto contours were on average larger than manual contours by up to 9%. Objective scores, D 2% and D 98% of the planning target volume, homogeneity and conformity indices, and coverage of normal tissue structures (lungs, heart, esophagus, spinal cord) at defined dose levels were not significantly different between plans (p = 0.22-0.94). Differences were statistically insignificant for the generalized equivalent uniform dose of the planning target volume (p = 0.19-0.94) and normal tissue complication probabilities for lung and esophagus (p = 0.13-0.47). Dosimetric differences >2% or >1 Gy were more frequent in patients with auto/manual volume differences ≥10% (p = 0.04). Conclusions: The applied deformable image registration algorithm produces clinically plausible auto contours in the majority of structures. At this stage clinical supervision of the auto contouring process is required, and manual interventions may become necessary. Before routine use, further investigations are required, particularly to reduce imaging artifacts

  11. Nanotechnology based targeted drug delivery.

    Science.gov (United States)

    Ruggiero, Carmelina; Pastorino, Laura; Herrera, Oscar L

    2010-01-01

    NANOTECHNOLOGY is having a great impact on many industrial applications, such as manufacturing, semiconductors, nanostructured materials and biotechnology. As relates to the latter, nanobiotechnology focuses on the ability to work at the molecular and atomic level to fabricate structures combining biological materials and synthetic materials, taking into account engineering, physics, chemistry, genomics and proteomics. The main goals relate to biosensors, nanosized microchips, and more generally to medical applications at the molecular level. Nanotechnology has been recently extensively applied to treatment and diagnosis of diseases and the new term nanomedicine has been introduced, for which several definitions have so far been proposed [1]-[3] which focus on the use of engineered nano-devices and nanostructures for diagnosis and treatment. One of the key aspects of nanomedicine is targeted drug delivery by nanoscale drug carriers. At present, 95 % of all new potential therapeutics have poor pharmaco kinetics and biopharmaceutical properties, there is therefore a great need to develop drug delivery [4] systems that convey the therapeutically active molecules only to the site of action, without affecting other organs and tissues [5]. This allows to lower required doses of drugs and to increase their therapeutic indices and safety profiles. It is possible to fabricate nanoparticles or nanocapsules with different properties as relates to drug encapsulation and release. A great amount of nanoscale systems for drug delivery has been investigated; they include liposomes, dendrimers, quantum dots, nanotubes, polymeric biodegradable nanoparticles and nanocapsules [6].

  12. Exploring model-based target discrimination metrics

    Science.gov (United States)

    Witus, Gary; Weathersby, Marshall

    2004-08-01

    Visual target discrimination has occurred when the observer can say "I see a target THERE!" and can designate the target location. Target discrimination occurs when a perceived shape is sufficiently similar one or more of the instances the observer has been trained on. Marr defined vision as "knowing what is where by seeing." Knowing "what" requires prior knowledge. Target discrimination requires model-based visual processing. Model-based signature metrics attempt to answer the question "to what extent does the target in the image resemble a training image?" Model-based signature metrics attempt to represent the effects of high-level top-down visual cognition, in addition to low-level bottom-up effects. Recent advances in realistic 3D target rendering and computer-vision object recognition have made model-based signature metrics more practical. The human visual system almost certainly does NOT use the same processing algorithms as computer vision object recognition, but some processing elements and the overall effects are similar. It remains to be determined whether model-based metrics explain the variance in human performance. The purpose of this paper is to explain and illustrate the model-based approach to signature metrics.

  13. WTS - Risk Based Resource Targeting (RBRT) -

    Data.gov (United States)

    Department of Transportation — The Risk Based Resource Targeting (RBRT) application supports a new SMS-structured process designed to focus on safety oversight of systems and processes rather than...

  14. Creation of RTOG compliant patient CT-atlases for automated atlas based contouring of local regional breast and high-risk prostate cancers.

    Science.gov (United States)

    Velker, Vikram M; Rodrigues, George B; Dinniwell, Robert; Hwee, Jeremiah; Louie, Alexander V

    2013-07-25

    Increasing use of IMRT to treat breast and prostate cancers at high risk of regional nodal spread relies on accurate contouring of targets and organs at risk, which is subject to significant inter- and intra-observer variability. This study sought to evaluate the performance of an atlas based deformable registration algorithm to create multi-patient CT based atlases for automated contouring. Breast and prostate multi-patient CT atlases (n = 50 and 14 respectively) were constructed to be consistent with RTOG consensus contouring guidelines. A commercially available software algorithm was evaluated by comparison of atlas-predicted contours against manual contours using Dice Similarity coefficients. High levels of agreement were demonstrated for prediction of OAR contours of lungs, heart, femurs, and minor editing required for the CTV breast/chest wall. CTVs generated for axillary nodes, supraclavicular nodes, prostate, and pelvic nodes demonstrated modest agreement. Small and highly variable structures, such as internal mammary nodes, lumpectomy cavity, rectum, penile bulb, and seminal vesicles had poor agreement. A method to construct and validate performance of CT-based multi-patient atlases for automated atlas based auto-contouring has been demonstrated, and can be adopted for clinical use in planning of local regional breast and high-risk prostate radiotherapy.

  15. Pronuclear Injection-Based Targeted Transgenesis.

    Science.gov (United States)

    Schilit, Samantha L P; Ohtsuka, Masato; Quadros, Rolen M; Gurumurthy, Channabasavaiah B

    2016-10-11

    Microinjection of DNA expression cassettes into fertilized zygotes has been a standard method for generating transgenic animal models. While efficient, the injected DNA integrates randomly into the genome, leading to potential disruption of endogenous genes or regulatory elements, variation in copy number, or integration into heterochromatic regions that inhibit transgene expression. A recently developed method addresses such pitfalls of traditional transgenesis by targeting the transgene to predetermined sites in the genome that can safely harbor exogenous DNA. This method, called Pronuclear Injection-based Targeted Transgenesis (PITT), employs an enzymatic transfer of exogenous DNA from a donor vector to a previously created landing-pad site in the mouse genome. DNA transfer is achieved using molecular tools such as the Cre-LoxP recombinase and PhiC31-attB/P integrase systems. Here, we provide protocols for performing PITT and an overview of the current PITT tools available to the research community. © 2016 by John Wiley & Sons, Inc. Copyright © 2016 John Wiley & Sons, Inc.

  16. [Resistance to target-based therapy and its circumvention].

    Science.gov (United States)

    Nishio, Kazuto

    2004-07-01

    Intrinsic and acquired resistance to molecular target therapy critically limits the outcome of cancer treatments. Target levels including quantitative and gene alteration should be determinants for the resistance. Downstream of the target molecules, drug metabolism, and drug transport influences the tumor sensitivity to molecular target therapy. The mechanisms of resistance to antibody therapy have not been fully clarified. Correlative clinical studies using these biomarkers of resistance are extremely important for circumvention of clinical resistance to target based therapy.

  17. Target recognition based on convolutional neural network

    Science.gov (United States)

    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.

  18. Panorama: a targeted proteomics knowledge base.

    Science.gov (United States)

    Sharma, Vagisha; Eckels, Josh; Taylor, Greg K; Shulman, Nicholas J; Stergachis, Andrew B; Joyner, Shannon A; Yan, Ping; Whiteaker, Jeffrey R; Halusa, Goran N; Schilling, Birgit; Gibson, Bradford W; Colangelo, Christopher M; Paulovich, Amanda G; Carr, Steven A; Jaffe, Jacob D; MacCoss, Michael J; MacLean, Brendan

    2014-09-05

    Panorama is a web application for storing, sharing, analyzing, and reusing targeted assays created and refined with Skyline,1 an increasingly popular Windows client software tool for targeted proteomics experiments. Panorama allows laboratories to store and organize curated results contained in Skyline documents with fine-grained permissions, which facilitates distributed collaboration and secure sharing of published and unpublished data via a web-browser interface. It is fully integrated with the Skyline workflow and supports publishing a document directly to a Panorama server from the Skyline user interface. Panorama captures the complete Skyline document information content in a relational database schema. Curated results published to Panorama can be aggregated and exported as chromatogram libraries. These libraries can be used in Skyline to pick optimal targets in new experiments and to validate peak identification of target peptides. Panorama is open-source and freely available. It is distributed as part of LabKey Server,2 an open source biomedical research data management system. Laboratories and organizations can set up Panorama locally by downloading and installing the software on their own servers. They can also request freely hosted projects on https://panoramaweb.org , a Panorama server maintained by the Department of Genome Sciences at the University of Washington.

  19. Defining a radiotherapy target with positron emission tomography

    International Nuclear Information System (INIS)

    Black, Quinten C.; Grills, Inga S.; Kestin, Larry L.; Wong, Ching-Yee O.; Wong, John W.; Martinez, Alvaro A.; Yan Di

    2004-01-01

    Ci/mL. Sphere images in each experiment were auto-contoured (simulating a GTV) using the threshold SUV that yielded a volume matching that of the known sphere volume. A regressive function was constructed to represent the relationship between the threshold SUV and the mean target SUV. This function was then applied to define the GTV of 15 NSCLC patients. The GTV volumes were compared to those determined by a fixed image intensity threshold proposed by other investigators. Results: There was a strong linear relationship between the threshold SUV and the mean target SUV. The linear regressive function derived was: threshold SUV = 0.307 x (mean target SUV) + 0.588. The background concentration and target volume indirectly affect the threshold SUV by way of their influence on the mean target SUV. We applied the linear regressive function, as well as a fixed image intensity threshold (42% of maximum intensity) to the sphere phantoms and 15 patients with NSCLC. The results indicated that a much smaller deviation occurred when the threshold SUV regressive function was utilized to estimate the phantom volume as compared to the fixed image intensity threshold. The average absolute difference between the two methods was 21% with respect to the true phantom volume. The deviation became even more pronounced when applied to true patient GTV volumes, with a mean difference between the two methods of 67%. This was largely due to a greater degree of heterogeneity in the SUV of tumors over phantoms. Conclusions: An FDG-PET-based GTV can be systematically defined using a threshold SUV according to the regressive function described above. The threshold SUV for defining the target is strongly dependent on the mean target SUV of the target, and can be uniquely determined through the proposed iteration process

  20. Prediction of potential drug targets based on simple sequence properties

    Directory of Open Access Journals (Sweden)

    Lai Luhua

    2007-09-01

    Full Text Available Abstract Background During the past decades, research and development in drug discovery have attracted much attention and efforts. However, only 324 drug targets are known for clinical drugs up to now. Identifying potential drug targets is the first step in the process of modern drug discovery for developing novel therapeutic agents. Therefore, the identification and validation of new and effective drug targets are of great value for drug discovery in both academia and pharmaceutical industry. If a protein can be predicted in advance for its potential application as a drug target, the drug discovery process targeting this protein will be greatly speeded up. In the current study, based on the properties of known drug targets, we have developed a sequence-based drug target prediction method for fast identification of novel drug targets. Results Based on simple physicochemical properties extracted from protein sequences of known drug targets, several support vector machine models have been constructed in this study. The best model can distinguish currently known drug targets from non drug targets at an accuracy of 84%. Using this model, potential protein drug targets of human origin from Swiss-Prot were predicted, some of which have already attracted much attention as potential drug targets in pharmaceutical research. Conclusion We have developed a drug target prediction method based solely on protein sequence information without the knowledge of family/domain annotation, or the protein 3D structure. This method can be applied in novel drug target identification and validation, as well as genome scale drug target predictions.

  1. A computational network analysis based on targets of antipsychotic agents.

    Science.gov (United States)

    Gao, Lei; Feng, Shuo; Liu, Zhao-Yuan; Wang, Jiu-Qiang; Qi, Ke-Ke; Wang, Kai

    2018-03-01

    Currently, numerous antipsychotic agents have been developed in the area of pharmacological treatment of schizophrenia. However, the molecular mechanism underlying multi targets of antipsychotics were yet to be explored. In this study we performed a computational network analysis based on targets of antipsychotic agents. We retrieved a total of 96 targets from 56 antipsychotic agents. By expression enrichment analysis, we identified that the expressions of antipsychotic target genes were significantly enriched in liver, brain, blood and corpus striatum. By protein-protein interaction (PPI) network analysis, a PPI network with 77 significantly interconnected target genes was generated. By historeceptomics analysis, significant brain region specific target-drug interactions were identified in targets of dopamine receptors (DRD1-Olanzapine in caudate nucleus and pons (P-valueantipsychotic targets and insights for molecular mechanism of antipsychotic agents. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Tracking target objects orbiting earth using satellite-based telescopes

    Science.gov (United States)

    De Vries, Willem H; Olivier, Scot S; Pertica, Alexander J

    2014-10-14

    A system for tracking objects that are in earth orbit via a constellation or network of satellites having imaging devices is provided. An object tracking system includes a ground controller and, for each satellite in the constellation, an onboard controller. The ground controller receives ephemeris information for a target object and directs that ephemeris information be transmitted to the satellites. Each onboard controller receives ephemeris information for a target object, collects images of the target object based on the expected location of the target object at an expected time, identifies actual locations of the target object from the collected images, and identifies a next expected location at a next expected time based on the identified actual locations of the target object. The onboard controller processes the collected image to identify the actual location of the target object and transmits the actual location information to the ground controller.

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

    Directory of Open Access Journals (Sweden)

    Suhas Vasaikar

    2016-11-01

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

  4. Nanopore-Based Target Sequence Detection.

    Directory of Open Access Journals (Sweden)

    Trevor J Morin

    Full Text Available The promise of portable diagnostic devices relies on three basic requirements: comparable sensitivity to established platforms, inexpensive manufacturing and cost of operations, and the ability to survive rugged field conditions. Solid state nanopores can meet all these requirements, but to achieve high manufacturing yields at low costs, assays must be tolerant to fabrication imperfections and to nanopore enlargement during operation. This paper presents a model for molecular engineering techniques that meets these goals with the aim of detecting target sequences within DNA. In contrast to methods that require precise geometries, we demonstrate detection using a range of pore geometries. As a result, our assay model tolerates any pore-forming method and in-situ pore enlargement. Using peptide nucleic acid (PNA probes modified for conjugation with synthetic bulk-adding molecules, pores ranging 15-50 nm in diameter are shown to detect individual PNA-bound DNA. Detection of the CFTRΔF508 gene mutation, a codon deletion responsible for ∼66% of all cystic fibrosis chromosomes, is demonstrated with a 26-36 nm pore size range by using a size-enhanced PNA probe. A mathematical framework for assessing the statistical significance of detection is also presented.

  5. Target based drug design - a reality in virtual sphere.

    Science.gov (United States)

    Verma, Saroj; Prabhakar, Yenamandra S

    2015-01-01

    The target based drug design approaches are a series of computational procedures, including visualization tools, to support the decision systems of drug design/discovery process. In the essence of biological targets shaping the potential lead/drug molecules, this review presents a comprehensive position of different components of target based drug design which include target identification, protein modeling, molecular dynamics simulations, binding/catalytic sites identification, docking, virtual screening, fragment based strategies, substructure treatment of targets in tackling drug resistance, in silico ADMET, structural vaccinology, etc along with the key issues involved therein and some well investigated case studies. The concepts and working of these procedures are critically discussed to arouse interest and to advance the drug research.

  6. miRNA-target prediction based on transcriptional regulation

    Directory of Open Access Journals (Sweden)

    Fujiwara Toyofumi

    2013-02-01

    Full Text Available Abstract Background microRNAs (miRNAs are tiny endogenous RNAs that have been discovered in animals and plants, and direct the post-transcriptional regulation of target mRNAs for degradation or translational repression via binding to the 3'UTRs and the coding exons. To gain insight into the biological role of miRNAs, it is essential to identify the full repertoire of mRNA targets (target genes. A number of computer programs have been developed for miRNA-target prediction. These programs essentially focus on potential binding sites in 3'UTRs, which are recognized by miRNAs according to specific base-pairing rules. Results Here, we introduce a novel method for miRNA-target prediction that is entirely independent of existing approaches. The method is based on the hypothesis that transcription of a miRNA and its target genes tend to be co-regulated by common transcription factors. This hypothesis predicts the frequent occurrence of common cis-elements between promoters of a miRNA and its target genes. That is, our proposed method first identifies putative cis-elements in a promoter of a given miRNA, and then identifies genes that contain common putative cis-elements in their promoters. In this paper, we show that a significant number of common cis-elements occur in ~28% of experimentally supported human miRNA-target data. Moreover, we show that the prediction of human miRNA-targets based on our method is statistically significant. Further, we discuss the random incidence of common cis-elements, their consensus sequences, and the advantages and disadvantages of our method. Conclusions This is the first report indicating prevalence of transcriptional regulation of a miRNA and its target genes by common transcription factors and the predictive ability of miRNA-targets based on this property.

  7. Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System

    Directory of Open Access Journals (Sweden)

    Ajmal Hinas

    2017-12-01

    Full Text Available In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

  8. Vision-Based Target Finding and Inspection of a Ground Target Using a Multirotor UAV System.

    Science.gov (United States)

    Hinas, Ajmal; Roberts, Jonathan M; Gonzalez, Felipe

    2017-12-17

    In this paper, a system that uses an algorithm for target detection and navigation and a multirotor Unmanned Aerial Vehicle (UAV) for finding a ground target and inspecting it closely is presented. The system can also be used for accurate and safe delivery of payloads or spot spraying applications in site-specific crop management. A downward-looking camera attached to a multirotor is used to find the target on the ground. The UAV descends to the target and hovers above the target for a few seconds to inspect the target. A high-level decision algorithm based on an OODA (observe, orient, decide, and act) loop was developed as a solution to address the problem. Navigation of the UAV was achieved by continuously sending local position messages to the autopilot via Mavros. The proposed system performed hovering above the target in three different stages: locate, descend, and hover. The system was tested in multiple trials, in simulations and outdoor tests, from heights of 10 m to 40 m. Results show that the system is highly reliable and robust to sensor errors, drift, and external disturbance.

  9. Information management data base for fusion target fabrication processes

    International Nuclear Information System (INIS)

    Reynolds, J.

    1983-01-01

    A computer-based data management system has been developed to handle data associated with target fabrication processes including glass microballoon characterization, gas filling, materials coating, and storage locations. The system provides automatic data storage and computation, flexible data entry procedures, fast access, automated report generation, and secure data transfer. It resides on a CDC CYBER 175 computer and is compatible with the CDC data base language Query Update, but is based on custom fortran software interacting directly with the CYBER's file management system. The described data base maintains detailed, accurate, and readily available records of fusion targets information

  10. Dim target detection method based on salient graph fusion

    Science.gov (United States)

    Hu, Ruo-lan; Shen, Yi-yan; Jiang, Jun

    2018-02-01

    Dim target detection is one key problem in digital image processing field. With development of multi-spectrum imaging sensor, it becomes a trend to improve the performance of dim target detection by fusing the information from different spectral images. In this paper, one dim target detection method based on salient graph fusion was proposed. In the method, Gabor filter with multi-direction and contrast filter with multi-scale were combined to construct salient graph from digital image. And then, the maximum salience fusion strategy was designed to fuse the salient graph from different spectral images. Top-hat filter was used to detect dim target from the fusion salient graph. Experimental results show that proposal method improved the probability of target detection and reduced the probability of false alarm on clutter background images.

  11. Deep-Learning-Based Drug-Target Interaction Prediction.

    Science.gov (United States)

    Wen, Ming; Zhang, Zhimin; Niu, Shaoyu; Sha, Haozhi; Yang, Ruihan; Yun, Yonghuan; Lu, Hongmei

    2017-04-07

    Identifying interactions between known drugs and targets is a major challenge in drug repositioning. In silico prediction of drug-target interaction (DTI) can speed up the expensive and time-consuming experimental work by providing the most potent DTIs. In silico prediction of DTI can also provide insights about the potential drug-drug interaction and promote the exploration of drug side effects. Traditionally, the performance of DTI prediction depends heavily on the descriptors used to represent the drugs and the target proteins. In this paper, to accurately predict new DTIs between approved drugs and targets without separating the targets into different classes, we developed a deep-learning-based algorithmic framework named DeepDTIs. It first abstracts representations from raw input descriptors using unsupervised pretraining and then applies known label pairs of interaction to build a classification model. Compared with other methods, it is found that DeepDTIs reaches or outperforms other state-of-the-art methods. The DeepDTIs can be further used to predict whether a new drug targets to some existing targets or whether a new target interacts with some existing drugs.

  12. Pentanol-based target material with polarized protons

    International Nuclear Information System (INIS)

    Bunyatova, E.I.

    1992-01-01

    1-pentanol is a promising material for a target with polarized protons owing to its high resistance to radiation damage. To develop the target, the solutions of 1-pentanol or 2-pentanol with complexes of pentavalent chromium ware investigated. The material based EHBA-Cr(V) solution in a glass-like matrix, consisting of 1-pentanol, 3-pentanol and 1,2-propanediol, was proposed as a target material. It was investigated by the electron paramagnetic resonance and differential scanning calorimetry methods. 24 refs.; 3 figs.; 1 tab

  13. PRICISE TARGET GEOLOCATION AND TRACKING BASED ON UAV VIDEO IMAGERY

    Directory of Open Access Journals (Sweden)

    H. R. Hosseinpoor

    2016-06-01

    Full Text Available There is an increasingly large number of applications for Unmanned Aerial Vehicles (UAVs from monitoring, mapping and target geolocation. However, most of commercial UAVs are equipped with low-cost navigation sensors such as C/A code GPS and a low-cost IMU on board, allowing a positioning accuracy of 5 to 10 meters. This low accuracy cannot be used in applications that require high precision data on cm-level. This paper presents a precise process for geolocation of ground targets based on thermal video imagery acquired by small UAV equipped with RTK GPS. The geolocation data is filtered using an extended Kalman filter, which provides a smoothed estimate of target location and target velocity. The accurate geo-locating of targets during image acquisition is conducted via traditional photogrammetric bundle adjustment equations using accurate exterior parameters achieved by on board IMU and RTK GPS sensors, Kalman filtering and interior orientation parameters of thermal camera from pre-flight laboratory calibration process. The results of this study compared with code-based ordinary GPS, indicate that RTK observation with proposed method shows more than 10 times improvement of accuracy in target geolocation.

  14. Target Detection Based on EBPSK Satellite Passive Radar

    Directory of Open Access Journals (Sweden)

    Lu Zeyuan

    2015-05-01

    Full Text Available Passive radar is a topic anti stealth technology with simple structure, and low cost. Radiation source model, signal transmission model, and target detection are the key points of passive radar technology research. The paper analyzes the characteristics of EBPSK signal modulation and target detection method aspect of spaceborne radiant source. By comparison with other satellite navigation and positioning system, the characteristics of EBPSK satellite passive radar system are analyzed. It is proved that the maximum detection range of EBPSK satellite signal can satisfy the needs of the proposed model. In the passive radar model, sparse representation is used to achieve high resolution DOA detection. The comparison with the real target track by simulation demonstrates that effective detection of airborne target using EBPSK satellite passive radar system based on sparse representation is efficient.

  15. Infrared small target enhancement based on variance difference

    Science.gov (United States)

    Nasiri, Mahdi; Chehresa, Saeed

    2017-05-01

    In surveillance and early warning systems, the enhancement of targets is a very important stage for the high reliability detection and tracking in Infrared images with complex backgrounds. In order to enhance small targets in an Infrared image and suppress the background clutter, consequently increasing the contrast between them, this paper proposes a method using a model for the target area with a three-layer patch-image model and based on the difference between the variance of the layers in the neighboring areas of the investigated pixel. Results of the experiments indicate that the proposed method is quite effective on the enhancement of small targets as well as suppression of the background clutter in IR images with a minimum false alarm rate. This is realized while the runtime of the proposed method is minimal compared to other commonly used methods, which makes it effective to be used in real time applications.

  16. Human MAP Tau Based Targeted Cytolytic Fusion Proteins

    Directory of Open Access Journals (Sweden)

    Olusiji A. Akinrinmade

    2017-06-01

    Full Text Available Some of the most promising small molecule toxins used to generate antibody drug conjugates (ADCs include anti-mitotic agents (e.g., auristatin and its derivatives which are designed to attack cancerous cells at their most vulnerable state during mitosis. We were interested in identifying a human cystostatic protein eventually showing comparable activities and allowing the generation of corresponding targeted fully human cytolytic fusion proteins. Recently, we identified the human microtubule associated protein tau (MAP tau, which binds specifically to tubulin and modulates the stability of microtubules, thereby blocking mitosis and presumably vesicular transport. By binding and stabilizing polymerized microtubule filaments, MAP tau-based fusion proteins skew microtubule dynamics towards cell cycle arrest and apoptosis. This biological activity makes rapidly proliferating cells (e.g., cancer and inflammatory cells an excellent target for MAP tau-based targeted treatments. Their superior selectivity for proliferating cells confers additional selectivity towards upregulated tumor-associated antigens at their surface, thereby preventing off-target related toxicity against normal cells bearing tumor-associated antigens at physiologically normal to low levels. In this review, we highlight recent findings on MAP tau-based targeted cytolytic fusion proteins reported in preclinical immunotherapeutic studies.

  17. Drug-target interaction prediction from PSSM based evolutionary information.

    Science.gov (United States)

    Mousavian, Zaynab; Khakabimamaghani, Sahand; Kavousi, Kaveh; Masoudi-Nejad, Ali

    2016-01-01

    The labor-intensive and expensive experimental process of drug-target interaction prediction has motivated many researchers to focus on in silico prediction, which leads to the helpful information in supporting the experimental interaction data. Therefore, they have proposed several computational approaches for discovering new drug-target interactions. Several learning-based methods have been increasingly developed which can be categorized into two main groups: similarity-based and feature-based. In this paper, we firstly use the bi-gram features extracted from the Position Specific Scoring Matrix (PSSM) of proteins in predicting drug-target interactions. Our results demonstrate the high-confidence prediction ability of the Bigram-PSSM model in terms of several performance indicators specifically for enzymes and ion channels. Moreover, we investigate the impact of negative selection strategy on the performance of the prediction, which is not widely taken into account in the other relevant studies. This is important, as the number of non-interacting drug-target pairs are usually extremely large in comparison with the number of interacting ones in existing drug-target interaction data. An interesting observation is that different levels of performance reduction have been attained for four datasets when we change the sampling method from the random sampling to the balanced sampling. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Classification and Target Group Selection Based Upon Frequent Patterns

    NARCIS (Netherlands)

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

    2000-01-01

    textabstractIn this technical report , two new algorithms based upon frequent patterns are proposed. One algorithm is a classification method. The other one is an algorithm for target group selection. In both algorithms, first of all, the collection of frequent patterns in the training set is

  19. Ground-based observations of Kepler asteroseismic targets

    DEFF Research Database (Denmark)

    Uyttterhoeven , K.; Karoff, Christoffer

    2010-01-01

    We present the ground-based activities within the different working groups of the Kepler Asteroseismic Science Consortium (KASC). The activities aim at the systematic characterization of the 5000+ KASC targets, and at the collection of ground-based follow-up time-series data of selected promising...... Kepler pulsators. So far, 36 different instruments at 31 telescopes on 23 different observatories in 12 countries are in use, and a total of more than 530 observing nights has been awarded....

  20. Acceptability of Service Targets for ICT-Based Healthcare.

    Science.gov (United States)

    Jeon, Eun Min; Seo, Hwa Jeong

    2016-10-01

    In order to adopt and activate telemedicine it is necessary to survey how medical staff, who are providers of medical service, and consumers, who are the service targets, perceive information and communication technology (ICT)-based healthcare service. This study surveyed the awareness and acceptability of ICT-based healthcare by involving service targets, specifically workers and students living in the Seoul and Gyeonggi regions who are consumers of healthcare service. To determine the correlation among awareness of ICT-based healthcare, the need for self-management, and acceptability, this study conducted a correlation analysis and a simple regression analysis. According to the responses to the questions on the need for ICT-based healthcare service by item, blood pressure (n = 279, 94.3%) and glucose (n = 277, 93.6%) were revealed to be the physiological signal monitoring area. Among the six measurement factors affecting ICT-based healthcare service acceptability, age, health concerns, and effect expectation had the most significant effects. As effect expectation increased, acceptability became 4.38 times higher ( p ICT-based healthcare service. The fact that acceptability is higher among people who have family disease history or greater health concerns may lead to service targets' more active participation. This study also confirmed that a policy to motivate active participation of those in their 40s (who had high prevalence rates) was needed.

  1. Radionuclide-Based Cancer Imaging Targeting the Carcinoembryonic Antigen

    Directory of Open Access Journals (Sweden)

    Hao Hong

    2008-01-01

    Full Text Available Carcinoembryonic antigen (CEA, highly expressed in many cancer types, is an important target for cancer diagnosis and therapy. Radionuclide-based imaging techniques (gamma camera, single photon emission computed tomography [SPECT] and positron emission tomography [PET] have been extensively explored for CEA-targeted cancer imaging both preclinically and clinically. Briefly, these studies can be divided into three major categories: antibody-based, antibody fragment-based and pretargeted imaging. Radiolabeled anti-CEA antibodies, reported the earliest among the three categories, typically gave suboptimal tumor contrast due to the prolonged circulation life time of intact antibodies. Subsequently, a number of engineered anti-CEA antibody fragments (e.g. Fab’, scFv, minibody, diabody and scFv-Fc have been labeled with a variety of radioisotopes for CEA imaging, many of which have entered clinical investigation. CEA-Scan (a 99mTc-labeled anti-CEA Fab’ fragment has already been approved by the United States Food and Drug Administration for cancer imaging. Meanwhile, pretargeting strategies have also been developed for CEA imaging which can give much better tumor contrast than the other two methods, if the system is designed properly. In this review article, we will summarize the current state-of-the-art of radionuclide-based cancer imaging targeting CEA. Generally, isotopes with short half-lives (e.g. 18F and 99mTc are more suitable for labeling small engineered antibody fragments while the isotopes with longer half-lives (e.g. 123I and 111In are needed for antibody labeling to match its relatively long circulation half-life. With further improvement in tumor targeting efficacy and radiolabeling strategies, novel CEA-targeted agents may play an important role in cancer patient management, paving the way to “personalized medicine”.

  2. Radar Target Classification using Recursive Knowledge-Based Methods

    DEFF Research Database (Denmark)

    Jochumsen, Lars Wurtz

    The topic of this thesis is target classification of radar tracks from a 2D mechanically scanning coastal surveillance radar. The measurements provided by the radar are position data and therefore the classification is mainly based on kinematic data, which is deduced from the position. The target...... been terminated. Therefore, an update of the classification results must be made for each measurement of the target. The data for this work are collected throughout the PhD and are both collected from radars and other sensors such as GPS....... classes used in this work are classes, which are normal for coastal surveillance e.g.~ships, helicopters, birds etc. The classifier must be recursive as all data of a track is not present at any given moment. If all data were available, it would be too late to classify the track, as the track would have...

  3. Radar Target Recognition Based on Stacked Denoising Sparse Autoencoder

    Directory of Open Access Journals (Sweden)

    Zhao Feixiang

    2017-04-01

    Full Text Available Feature extraction is a key step in radar target recognition. The quality of the extracted features determines the performance of target recognition. However, obtaining the deep nature of the data is difficult using the traditional method. The autoencoder can learn features by making use of data and can obtain feature expressions at different levels of data. To eliminate the influence of noise, the method of radar target recognition based on stacked denoising sparse autoencoder is proposed in this paper. This method can extract features directly and efficiently by setting different hidden layers and numbers of iterations. Experimental results show that the proposed method is superior to the K-nearest neighbor method and the traditional stacked autoencoder.

  4. Target Image Matching Algorithm Based on Binocular CCD Ranging

    Directory of Open Access Journals (Sweden)

    Dongming Li

    2014-01-01

    Full Text Available This paper proposed target image in a subpixel level matching algorithm for binocular CCD ranging, which is based on the principle of binocular CCD ranging. In the paper, firstly, we introduced the ranging principle of the binocular ranging system and deduced a binocular parallax formula. Secondly, we deduced the algorithm which was named improved cross-correlation matching algorithm and cubic surface fitting algorithm for target images matched, and it could achieve a subpixel level matching for binocular CCD ranging images. Lastly, through experiment we have analyzed and verified the actual CCD ranging images, then analyzed the errors of the experimental results and corrected the formula of calculating system errors. Experimental results showed that the actual measurement accuracy of a target within 3 km was higher than 0.52%, which meet the accuracy requirements of the high precision binocular ranging.

  5. Folate-targeted docetaxel-lipid-based-nanosuspensions for active-targeted cancer therapy.

    Science.gov (United States)

    Wang, Lili; Li, Min; Zhang, Na

    2012-01-01

    The purpose of this study was to develop two novel drug delivery systems based on biodegradable docetaxel-lipid-based-nanosuspensions. The first one was poly(ethylene glycol)- modified docetaxel-lipid-based-nanosuspensions (pLNS). It was developed to increase the cycle time of the drug within the body and enhance the accumulation of the drug at the tumor site. The second one was targeted docetaxel-lipid-based-nanosuspensions (tLNS) using folate as the target ligand. The tLNS could target the tumor cells that overexpressed folate receptor (FR). The morphology, particle size, and zeta potential of pLNS and tLNS were characterized, respectively. The in vitro cytotoxicity evaluation of Duopafei(®), pLNS, and tLNS were performed in human hepatocellular liver carcinoma HepG2 (FR-) and B16 (FR+) cells, respectively. The in vivo antitumor efficacy and pharmacokinetics, as well as the drug tissue distribution, were evaluated in Kunming mice bearing B16 cells. The particle size of pLNS was 204.2 ± 6.18 nm and tLNS had a mean particle size of 220.6 ± 9.54 nm. Cytotoxicity of tLNS against B16 (FR+) cell lines was superior to pLNS (P < 0.05), while there was no significant difference in the half maximum inhibitory concentration values for HepG2 (FR-) cells between pLNS and tLNS. The results of the in vivo antitumor efficacy evaluation showed that tLNS exhibited higher antitumor efficacy by reducing tumor volume (P < 0.01) compared with Duopafei and pLNS, respectively. The results of the in vivo biodistribution study indicate that the better antitumor efficacy of tLNS was attributed to the increased accumulation of the drug in the tumor.

  6. Targeted cellular ablation based on the morphology of malignant cells

    Science.gov (United States)

    Ivey, Jill W.; Latouche, Eduardo L.; Sano, Michael B.; Rossmeisl, John H.; Davalos, Rafael V.; Verbridge, Scott S.

    2015-11-01

    Treatment of glioblastoma multiforme (GBM) is especially challenging due to a shortage of methods to preferentially target diffuse infiltrative cells, and therapy-resistant glioma stem cell populations. Here we report a physical treatment method based on electrical disruption of cells, whose action depends strongly on cellular morphology. Interestingly, numerical modeling suggests that while outer lipid bilayer disruption induced by long pulses (~100 μs) is enhanced for larger cells, short pulses (~1 μs) preferentially result in high fields within the cell interior, which scale in magnitude with nucleus size. Because enlarged nuclei represent a reliable indicator of malignancy, this suggested a means of preferentially targeting malignant cells. While we demonstrate killing of both normal and malignant cells using pulsed electric fields (PEFs) to treat spontaneous canine GBM, we proposed that properly tuned PEFs might provide targeted ablation based on nuclear size. Using 3D hydrogel models of normal and malignant brain tissues, which permit high-resolution interrogation during treatment testing, we confirmed that PEFs could be tuned to preferentially kill cancerous cells. Finally, we estimated the nuclear envelope electric potential disruption needed for cell death from PEFs. Our results may be useful in safely targeting the therapy-resistant cell niches that cause recurrence of GBM tumors.

  7. Moving Beyond Motive-based categories of Targeted Violence

    Energy Technology Data Exchange (ETDEWEB)

    Weine, Stevan [Univ. of Illinois, Chicago, IL (United States); Cohen, John [Rutgers Univ., New Brunswick, NJ (United States); Brannegan, David [Argonne National Lab. (ANL), Argonne, IL (United States)

    2015-10-01

    Today’s categories for responding to targeted violence are motive-based and tend to drive policies, practices, training, media coverage, and research. These categories are based on the assumption that there are significant differences between ideological and non-ideological actors and between domestic and international actors. We question the reliance on these categories and offer an alternative way to frame the response to multiple forms of targeted violence. We propose adopting a community-based multidisciplinary approach to assess risk and provide interventions that are focused on the pre-criminal space. We describe four capabilities that should be implemented locally by establishing and maintaining multidisciplinary response teams that combine community and law-enforcement components: (1) community members are educated, making them better able to identify and report patterns associated with elevated risk for violence; (2) community-based professionals are trained to assess the risks for violent behavior posed by individuals; (3) community-based professionals learn to implement strategies that directly intervene in causal factors for those individuals who are at elevated risk; and (4) community-based professionals learn to monitor and assess an individual’s risk for violent behaviors on an ongoing basis. Community-based multidisciplinary response teams have the potential to identify and help persons in the pre-criminal space and to reduce barriers that have traditionally impeded community/law-enforcement collaboration.

  8. Scattering Mechanism Identification Based on Polarimetric HRRP of Manmade Target

    Directory of Open Access Journals (Sweden)

    Wu Jiani

    2016-04-01

    Full Text Available In this paper, we analyze the space polarization and frequency dispersion characteristics of the polarimetric High Resolution Range Profile (HRRP of manmade targets. We integrate these characteristics and propose a novel scheme for scattering mechanism identification. Using a polarization decomposition technique, the scheme first identifies the scattering mechanism of the scattering centers. Specially, it uses an algorithm to compensate for the polarization orientation angle in order to decrease the errors in judgment caused by the varying azimuth. Then, based on the frequency dispersion characteristics, we design threedimensional parameters to discriminate between the scattering centers, in order to decrease the inaccuracy in the discriminations. Finally, we conduct simulations based on electromagnetic data to validate the feasibility of the proposed scheme and to demonstrate that it provides a basis for practical use in target recognition.

  9. Moving Target Information Extraction Based on Single Satellite Image

    Directory of Open Access Journals (Sweden)

    ZHAO Shihu

    2015-03-01

    Full Text Available The spatial and time variant effects in high resolution satellite push broom imaging are analyzed. A spatial and time variant imaging model is established. A moving target information extraction method is proposed based on a single satellite remote sensing image. The experiment computes two airplanes' flying speed using ZY-3 multispectral image and proves the validity of spatial and time variant model and moving information extracting method.

  10. Atlas-based identification of targets for functional radiosurgery

    International Nuclear Information System (INIS)

    Stancanello, Joseph; Romanelli, Pantaleo; Modugno, Nicola; Cerveri, Pietro; Ferrigno, Giancarlo; Uggeri, Fulvio; Cantore, Giampaolo

    2006-01-01

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

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

    Science.gov (United States)

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

    2018-04-01

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

  12. Research on moving target defense based on SDN

    Science.gov (United States)

    Chen, Mingyong; Wu, Weimin

    2017-08-01

    An address mutation strategy was proposed. This strategy provided an unpredictable change in address, replacing the real address of the packet forwarding process and path mutation, thus hiding the real address of the host and path. a mobile object defense technology based on Spatio-temporal Mutation on this basis is proposed, Using the software Defined Network centralized control architecture advantage combines sFlow traffic monitoring technology and Moving Target Defense. A mutated time period which can be changed in real time according to the network traffic is changed, and the destination address is changed while the controller abruptly changes the address while the data packet is transferred between the switches to construct a moving target, confusing the host within the network, thereby protecting the host and network.

  13. Graphite oxide based targets applied in laser matter interaction

    Science.gov (United States)

    Cutroneo, Mariapompea; Torrisi, Lorenzo; Badziak, Jan; Rosinski, Marcin; Havranek, Vladimir; Mackova, Anna; Malinsky, Petr; Sofer, Zdenek; Luxa, Jan; Cannavò, Antonino; Lorincik, Jan

    2018-01-01

    In the present work, we propose the production of a hybrid graphene based material suitable to be laser irradiated with the aim to produce quasi-monoenergetic proton beams using a femtosecond laser system. The unique lattice structure of the irradiated solid thin target can affect the inside electron propagation, their outgoing from the rear side of a thin foil, and subsequently the plasma ion acceleration. The produced targets, have been characterized in composition, roughness and structure and for completeness irradiated. The yield and energy of the ions emitted from the laser-generated plasma have been monitored and the emission of proton stream profile exhibited an acceleration of the order of several MeVs/charge state.

  14. Multimodality Imaging with Silica-Based Targeted Nanoparticle Platforms

    International Nuclear Information System (INIS)

    Lewis, Jason S.

    2012-01-01

    Objectives: To synthesize and characterize a C-Dot silica-based nanoparticle containing 'clickable' groups for the subsequent attachment of targeting moieties (e.g., peptides) and multiple contrast agents (e.g., radionuclides with high specific activity) (1,2). These new constructs will be tested in suitable tumor models in vitro and in vivo to ensure maintenance of target-specificity and high specific activity. Methods: Cy5 dye molecules are cross-linked to a silica precursor which is reacted to form a dye-rich core particle. This core is then encapsulated in a layer of pure silica to create the core-shell C-Dot (Figure 1) (2). A 'click' chemistry approach has been used to functionalize the silica shell with radionuclides conferring high contrast and specific activity (e.g. 64Cu and 89Zr) and peptides for tumor targeting (e.g. cRGD and octreotate) (3). Based on the selective Diels-Alder reaction between tetrazine and norbornene, the reaction is bioorthogonal, highyielding, rapid, and water-compatible. This radiolabeling approach has already been employed successfully with both short peptides (e.g. octreotate) and antibodies (e.g. trastuzumab) as model systems for the ultimate labeling of the nanoparticles (1). Results: PEGylated C-Dots with a Cy5 core and labeled with tetrazine have been synthesized (d = 55 nm, zeta potential = -3 mV) reliably and reproducibly and have been shown to be stable under physiological conditions for up to 1 month. Characterization of the nanoparticles revealed that the immobilized Cy5 dye within the C-Dots exhibited fluorescence intensities over twice that of the fluorophore alone. The nanoparticles were successfully radiolabeled with Cu-64. Efforts toward the conjugation of targeting peptides (e.g. cRGD) are underway. In vitro stability, specificity, and uptake studies as well as in vivo imaging and biodistribution investigations will be presented. Conclusions: C-Dot silica-based nanoparticles offer a robust, versatile, and multi

  15. Multimodality Imaging with Silica-Based Targeted Nanoparticle Platforms

    Energy Technology Data Exchange (ETDEWEB)

    Jason S. Lewis

    2012-04-09

    Objectives: To synthesize and characterize a C-Dot silica-based nanoparticle containing 'clickable' groups for the subsequent attachment of targeting moieties (e.g., peptides) and multiple contrast agents (e.g., radionuclides with high specific activity) [1,2]. These new constructs will be tested in suitable tumor models in vitro and in vivo to ensure maintenance of target-specificity and high specific activity. Methods: Cy5 dye molecules are cross-linked to a silica precursor which is reacted to form a dye-rich core particle. This core is then encapsulated in a layer of pure silica to create the core-shell C-Dot (Figure 1) [2]. A 'click' chemistry approach has been used to functionalize the silica shell with radionuclides conferring high contrast and specific activity (e.g. 64Cu and 89Zr) and peptides for tumor targeting (e.g. cRGD and octreotate) [3]. Based on the selective Diels-Alder reaction between tetrazine and norbornene, the reaction is bioorthogonal, highyielding, rapid, and water-compatible. This radiolabeling approach has already been employed successfully with both short peptides (e.g. octreotate) and antibodies (e.g. trastuzumab) as model systems for the ultimate labeling of the nanoparticles [1]. Results: PEGylated C-Dots with a Cy5 core and labeled with tetrazine have been synthesized (d = 55 nm, zeta potential = -3 mV) reliably and reproducibly and have been shown to be stable under physiological conditions for up to 1 month. Characterization of the nanoparticles revealed that the immobilized Cy5 dye within the C-Dots exhibited fluorescence intensities over twice that of the fluorophore alone. The nanoparticles were successfully radiolabeled with Cu-64. Efforts toward the conjugation of targeting peptides (e.g. cRGD) are underway. In vitro stability, specificity, and uptake studies as well as in vivo imaging and biodistribution investigations will be presented. Conclusions: C-Dot silica-based nanoparticles offer a robust

  16. Tailoring peritoneal dialysis fluid for optimal acid-base targets.

    Science.gov (United States)

    Feriani, Mariano

    2009-01-01

    Mild derangements of acid-base status are common features in peritoneal dialysis patients, metabolic acidosis being the most frequent alteration. One of the main tasks of dialysis is to correct these derangements and the target is the normalization of the acid-base parameters since they affect several organs and functions. Since factors affecting acid-base homeostasis are intrinsic characteristics of the individual patient (metabolic acid production, distribution space for bicarbonate, dialytic prescription, etc.), it is not surprising that only relatively few patients achieve the normal range. Only a certain modulation of buffer infusion by using different buffer concentrations in the dialysis fluid may ensure a good correction in a large percentage of patients.

  17. SAR Target Recognition with Feature Fusion Based on Stacked Autoencoder

    Directory of Open Access Journals (Sweden)

    Kang Miao

    2017-04-01

    Full Text Available A feature fusion algorithm based on a Stacked AutoEncoder (SAE for Synthetic Aperture Rader (SAR imagery is proposed in this paper. Firstly, 25 baseline features and Three-Patch Local Binary Patterns (TPLBP features are extracted. Then, the features are combined in series and fed into the SAE network, which is trained by a greedy layer-wise method. Finally, the softmax classifier is employed to fine tune the SAE network for better fusion performance. Additionally, the Gabor texture features of SAR images are extracted, and the fusion experiments between different features are carried out. The results show that the baseline features and TPLBP features have low redundancy and high complementarity, which makes the fused feature more discriminative. Compared with the SAR target recognition algorithm based on SAE or CNN (Convolutional Neural Network, the proposed method simplifies the network structure and increases the recognition accuracy and efficiency. 10-classes SAR targets based on an MSTAR dataset got a classification accuracy up to 95.88%, which verifies the effectiveness of the presented algorithm.

  18. A moving target detecting and tracking system based on DSP

    Science.gov (United States)

    Cai, Daonan; Zhao, Yuejin; Liu, Ming; Dong, Liquan; Liu, Xiaohua

    2018-01-01

    In order to solve the target fast tracking problem in embedded system, a moving target detecting and tracking algorithm based on a combination of three-frame difference and template matching is proposed. The system utilizes DSP to design a set of image processing equipment and DSP uses TI company's DM6437.Three-frame difference can detect a initial position of the target, then Mean Normalized Product Correlation(NNPROD) template matching algorithm was utilized in a partial area to achieve a precise position and reduce the amount of calculation. The algorithm utilized four templates and image compression to fit pose and scale changes when moving. To meet the real-time requirement, an improved algorithm of NNPROD was proposed under certain lighting conditions, what ' s more the C language code was optimized and TI company's highly optimized VLIB vision library was reasonably utilized. After several tests, the results showed that NNPROD can fit the changing of environmental light well, but more time was needed. The improved method can still work well with the changes of pose and scale when the light changes less intensely , and the processing speed of the improved method increased from the previous 11F / s to 23F / s.

  19. Financing Target and Resale Pricing in Reward-Based Crowdfunding

    Directory of Open Access Journals (Sweden)

    Lei Xu

    2018-04-01

    Full Text Available Resale is an effective tool for reward-based crowdfunding creators to make more profit after crowdfunding successfully. On the one hand, funds raised during the crowdfunding affect the resale pricing as a capital constraint; on the other hand, backers’ strategic purchasing behavior in the resale stage can also disturb the creator’s financing target decision-making through affecting resale pricing. In view of this, this paper builds a two-stage crowdfunding model to examine the interaction between the financing target and resale pricing in the presence of strategic backers. The results show that a lower financing amount leads to higher prices in the resale stage due to the rationing effect, and suppresses price volatility due to strategic purchasing behavior. In contrast, a higher financing amount enables the creator to build a large capacity, which does not restrict the resale prices and profit. Besides, in the context of high unit production cost or high backer patience level, there is no need for the creator to set a high financing target at the risk of crowdfunding failure.

  20. NETWORK BASED BUSINESS MODEL INNOVATION TARGETING THE BOP MARKET

    DEFF Research Database (Denmark)

    Ravn, Jacob; Kroghstrup Nielsen, Martin; Lindgren, Peter

    2009-01-01

    Through innovation of products, process and business models targeting the needs of 4 billion poor people living at "the base of pyramid" (BoP) (Prahalad & Hart 2002) in developing countries the private sector can actively support poverty alleviation and at the same time reach new untouched market...... countries seems to show up in the literature: The technological line - exemplified by the - exemplified by the Life Straw business model - a high tech "straw" consisting of 12 chemical filters to purify water - an example of technology driven innovation to meet the BoP demands for clean water (Kandachar...

  1. [A new calibration transfer method based on target factor analysis].

    Science.gov (United States)

    Wang, Yan-bin; Yuan, Hong-fu; Lu, Wan-zhen

    2005-03-01

    A new calibration transfer method based on target factor analysis is proposed.The performance of the new method compared with the piecewise direct standardization method. This method was applied to two data sets, of which one is a simulation data set, and the other is an NIR data set composed of benzene, toluene, xylene and isooctane. The results obtained with this new method are at least as well as those obtained by PDS with the biggest improvement occurring when the spectra have some non-linear responses.

  2. Rhamnogalacturonan-I Based Microcapsules for Targeted Drug Release.

    Science.gov (United States)

    Svagan, Anna J; Kusic, Anja; De Gobba, Cristian; Larsen, Flemming H; Sassene, Philip; Zhou, Qi; van de Weert, Marco; Mullertz, Anette; Jørgensen, Bodil; Ulvskov, Peter

    2016-01-01

    Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were loaded with a fluorescent dye (model drug). The capsules showed negligible and very little in vitro release when subjected to media simulating gastric and intestinal fluids, respectively. However, upon exposure to a cocktail of commercial RG-I cleaving enzymes, ~ 9 times higher release was observed, demonstrating that the capsules can be opened by enzymatic degradation. The combined results suggest a potential platform for targeted drug delivery in the terminal gastro-intestinal tract.

  3. In silico design of targeted SRM-based experiments

    Directory of Open Access Journals (Sweden)

    Nahnsen Sven

    2012-11-01

    Full Text Available Abstract Selected reaction monitoring (SRM-based proteomics approaches enable highly sensitive and reproducible assays for profiling of thousands of peptides in one experiment. The development of such assays involves the determination of retention time, detectability and fragmentation properties of peptides, followed by an optimal selection of transitions. If those properties have to be identified experimentally, the assay development becomes a time-consuming task. We introduce a computational framework for the optimal selection of transitions for a given set of proteins based on their sequence information alone or in conjunction with already existing transition databases. The presented method enables the rapid and fully automated initial development of assays for targeted proteomics. We introduce the relevant methods, report and discuss a step-wise and generic protocol and we also show that we can reach an ad hoc coverage of 80 % of the targeted proteins. The presented algorithmic procedure is implemented in the open-source software package OpenMS/TOPP.

  4. Design and implementation of location-based wireless targeted advertising

    Science.gov (United States)

    Li, Benjamin; Xu, Deyin

    2001-10-01

    As advertisements are time and location sensitive, a challenge for wireless marketing is to have advertisements delivered when and where they are most convenient. In this paper we introduce a two-stage auction model for location-based wireless targeted advertising. This system extends the notion of location-based service by using location information to target advertising, and does so specifically by enabling advertisers to specify their preferences and bid for advertisement delivery, where those preferences are then used in a subsequent automated auction of actual deliveries to wireless data users. The automated auction in the second stage is especially effective because it can use information about the individual user profile data, including customer relationship management system contents as well as location from the wireless system's location management service, including potentially location history such as current trajectory from recent history and longer-term historical trip records for that user. Through two-stage auction, real-time bidding by advertisers and matching ads contents to mobile users help advertising information reach maximal value.

  5. Rhamnogalacturonan-I based microcapsules for targeted drug release

    DEFF Research Database (Denmark)

    Svagan, Anna J.; Kusic, Anja; De Gobba, Cristian

    2016-01-01

    Drug targeting to the colon via the oral administration route for local treatment of e.g. inflammatory bowel disease and colonic cancer has several advantages such as needle-free administration and low infection risk. A new source for delivery is plant-polysaccharide based delivery platforms...... such as Rhamnogalacturonan-I (RG-I). In the gastro-intestinal tract the RG-I is only degraded by the action of the colonic microflora. For assessment of potential drug delivery properties, RG-I based microcapsules (~1 μm in diameter) were prepared by an interfacial poly-addition reaction. The cross-linked capsules were...... loaded with a fluorescent dye (model drug). The capsules showed negligible and very little in vitro release when subjected to media simulating gastric and intestinal fluids, respectively. However, upon exposure to a cocktail of commercial RG-I cleaving enzymes, ~ 9 times higher release was observed...

  6. Discovery based and targeted Mass Spectrometry in farm animal proteomics

    DEFF Research Database (Denmark)

    Bendixen, Emøke

    2013-01-01

    for investigating farm animal biology. SRM is particularly important for validation biomarker candidates This talk will introduce the use of different mass spectrometry approaches through examples related to food quality and animal welfare, including studies of gut health in pigs, host pathogen interactions......Technological advances in mass spectrometry have greatly improved accuracy and speed of analyses of proteins and biochemical pathways. These proteome technologies have transformed research and diagnostic methods in the biomedical fields, and in food and farm animal sciences proteomics can be used...... be monitored to improve welfare in large industrial settings of current livestock industry. The combination of discovery based LC-MS/MS methods and the more hypothesis-based targeted mass spectrometry method commonly referred to as selected reaction monitoring or SRM, provide a powerful approach...

  7. Augmenting atlas-based liver segmentation for radiotherapy treatment planning by incorporating image features proximal to the atlas contours

    Science.gov (United States)

    Li, Dengwang; Liu, Li; Chen, Jinhu; Li, Hongsheng; Yin, Yong; Ibragimov, Bulat; Xing, Lei

    2017-01-01

    30 liver cases suggested that the technique was capable to reliably segment liver cases from CT, 4D-CT, and CBCT images with little human interaction. The accuracy and speed of the proposed method are quantitatively validated by comparing automatic segmentation results with the manual delineation results. The Jaccard similarity metric between the automatically generated liver contours obtained by the proposed method and the physician delineated results are on an average 90%-96% for planning images. Incorporation of image features into the library contours improves the currently available atlas-based auto-contouring techniques and provides a clinically practical solution for auto-segmentation. The proposed mountainous narrow shell atlas based method can achieve efficient automatic liver propagation for CT, 4D-CT and CBCT images with following treatment planning and should find widespread application in future treatment planning systems.

  8. Augmenting atlas-based liver segmentation for radiotherapy treatment planning by incorporating image features proximal to the atlas contours.

    Science.gov (United States)

    Li, Dengwang; Liu, Li; Chen, Jinhu; Li, Hongsheng; Yin, Yong; Ibragimov, Bulat; Xing, Lei

    2017-01-07

    30 liver cases suggested that the technique was capable to reliably segment liver cases from CT, 4D-CT, and CBCT images with little human interaction. The accuracy and speed of the proposed method are quantitatively validated by comparing automatic segmentation results with the manual delineation results. The Jaccard similarity metric between the automatically generated liver contours obtained by the proposed method and the physician delineated results are on an average 90%-96% for planning images. Incorporation of image features into the library contours improves the currently available atlas-based auto-contouring techniques and provides a clinically practical solution for auto-segmentation. The proposed mountainous narrow shell atlas based method can achieve efficient automatic liver propagation for CT, 4D-CT and CBCT images with following treatment planning and should find widespread application in future treatment planning systems.

  9. A Target Advertisement System Based on TV Viewer's Profile Reasoning

    Science.gov (United States)

    Lim, Jeongyeon; Kim, Munjo; Lee, Bumshik; Kim, Munchurl; Lee, Heekyung; Lee, Han-Kyu

    With the rapidly growing Internet, the Internet broadcasting and web casting service have been one of the well-known services. Specially, it is expected that the IPTV service will be one of the principal services in the broadband network [2]. However, the current broadcasting environment is served for the general public and requires the passive attitude to consume the TV programs. For the advanced broadcasting environments, various research of the personalized broadcasting is needed. For example, the current unidirectional advertisement provides to the TV viewers the advertisement contents, depending on the popularity of TV programs, the viewing rates, the age groups of TV viewers, and the time bands of the TV programs being broadcast. It is not an efficient way to provide the useful information to the TV viewers from customization perspective. If a TV viewer does not need particular advertisement contents, then information may be wasteful to the TV viewer. Therefore, it is expected that the target advertisement service will be one of the important services in the personalized broadcasting environments. The current research in the area of the target advertisement classifies the TV viewers into clustered groups who have similar preference. The digital TV collaborative filtering estimates the user's favourite advertisement contents by using the usage history [1, 4, 5]. In these studies, the TV viewers are required to provide their profile information such as the gender, job, and ages to the service providers via a PC or Set-Top Box (STB) which is connected to digital TV. Based on explicit information, the advertisement contents are provided to the TV viewers in a customized way with tailored advertisement contents. However, the TV viewers may dislike exposing to the service providers their private information because of the misuse of it. In this case, it is difficult to provide appropriate target advertisement service.

  10. Targeted albumin-based nanoparticles for delivery of amphipathic drugs.

    Science.gov (United States)

    Xu, Rongzuo; Fisher, Michael; Juliano, R L

    2011-05-18

    We report the preparation and physical and biological characterization of human serum albumin-based micelles of approximately 30 nm diameter for the delivery of amphipathic drugs, represented by doxorubicin. The micelles were surface conjugated with cyclic RGD peptides to guide selective delivery to cells expressing the α(v)β(3) integrin. Multiple poly(ethylene glycol)s (PEGs) with molecular weight of 3400 Da were used to form a hydrophilic outer layer, with the inner core formed by albumin conjugated with doxorubicin via disulfide bonds. Additional doxorubicin was physically adsorbed into this core to attain a high drug loading capacity, where each albumin was associated with about 50 doxorubicin molecules. The formed micelles were stable in serum but continuously released doxorubicin when incubated with free thiols at concentrations mimicking the intracellular environment. When incubated with human melanoma cells (M21+) that express the α(v)β(3) integrin, higher uptake and longer retention of doxorubicin was observed with the RGD-targeted micelles than in the case of untargeted control micelles or free doxorubicin. Consequently, the RGD-targeted micelles manifested cytotoxicity at lower doses of drug than control micelles or free drug.

  11. Feature extraction algorithm for space targets based on fractal theory

    Science.gov (United States)

    Tian, Balin; Yuan, Jianping; Yue, Xiaokui; Ning, Xin

    2007-11-01

    In order to offer a potential for extending the life of satellites and reducing the launch and operating costs, satellite servicing including conducting repairs, upgrading and refueling spacecraft on-orbit become much more frequently. Future space operations can be more economically and reliably executed using machine vision systems, which can meet real time and tracking reliability requirements for image tracking of space surveillance system. Machine vision was applied to the research of relative pose for spacecrafts, the feature extraction algorithm was the basis of relative pose. In this paper fractal geometry based edge extraction algorithm which can be used in determining and tracking the relative pose of an observed satellite during proximity operations in machine vision system was presented. The method gets the gray-level image distributed by fractal dimension used the Differential Box-Counting (DBC) approach of the fractal theory to restrain the noise. After this, we detect the consecutive edge using Mathematical Morphology. The validity of the proposed method is examined by processing and analyzing images of space targets. The edge extraction method not only extracts the outline of the target, but also keeps the inner details. Meanwhile, edge extraction is only processed in moving area to reduce computation greatly. Simulation results compared edge detection using the method which presented by us with other detection methods. The results indicate that the presented algorithm is a valid method to solve the problems of relative pose for spacecrafts.

  12. Improving routing efficiency through intermediate target based geographic routing

    Directory of Open Access Journals (Sweden)

    Zongming Fei

    2015-08-01

    Full Text Available The greedy strategy of geographical routing may cause the local minimum problem when there is a hole in the routing area. It depends on other strategies such as perimeter routing to find a detour path, which can be long and result in inefficiency of the routing protocol. In this paper, we propose a new approach called Intermediate Target based Geographic Routing (ITGR to solve the long detour path problem. The basic idea is to use previous experience to determine the destination areas that are shaded by the holes. The novelty of the approach is that a single forwarding path can be used to determine a shaded area that may cover many destination nodes. We design an efficient method for the source to find out whether a destination node belongs to a shaded area. The source then selects an intermediate node as the tentative target and greedily forwards packets to it, which in turn forwards the packet to the final destination by greedy routing. ITGR can combine multiple shaded areas to improve the efficiency of representation and routing. We perform simulations and demonstrate that ITGR significantly reduces the routing path length, compared with existing geographic routing protocols.

  13. Facilities for preparing actinide or fission product-based targets

    CERN Document Server

    Sors, M

    1999-01-01

    Research and development work is currently in progress in France on the feasibility of transmutation of very long-lived radionuclides such as americium, blended with an inert medium such as magnesium oxide and pelletized for irradiation in a fast neutron reactor. The process is primarily designed to produce ceramics for nuclear reactors, but could also be used to produce targets for accelerators. The Actinide Development Laboratory is part of the ATALANTE complex at Marcoule, where the CEA investigates reprocessing, liquid and solid waste treatment and vitrification processes. The laboratory produces radioactive sources; after use, their constituents are recycled, notably through R and D programs requiring such materials. Recovered americium is purified, characterized and transformed for an experiment known as ECRIX, designed to demonstrate the feasibility of fabricating americium-based ceramics and to determine the reactor transmutation coefficients.

  14. Influence of different contributions of scatter and attenuation on the threshold values in contrast-based algorithms for volume segmentation.

    Science.gov (United States)

    Matheoud, Roberta; Della Monica, Patrizia; Secco, Chiara; Loi, Gianfranco; Krengli, Marco; Inglese, Eugenio; Brambilla, Marco

    2011-01-01

    The aim of this work is to evaluate the role of different amount of attenuation and scatter on FDG-PET image volume segmentation using a contrast-oriented method based on the target-to-background (TB) ratio and target dimensions. A phantom study was designed employing 3 phantom sets, which provided a clinical range of attenuation and scatter conditions, equipped with 6 spheres of different volumes (0.5-26.5 ml). The phantoms were: (1) the Hoffman 3-dimensional brain phantom, (2) a modified International Electro technical Commission (IEC) phantom with an annular ring of water bags of 3 cm thickness fit over the IEC phantom, and (3) a modified IEC phantom with an annular ring of water bags of 9 cm. The phantoms cavities were filled with a solution of FDG at 5.4 kBq/ml activity concentration, and the spheres with activity concentration ratios of about 16, 8, and 4 times the background activity concentration. Images were acquired with a Biograph 16 HI-REZ PET/CT scanner. Thresholds (TS) were determined as a percentage of the maximum intensity in the cross section area of the spheres. To reduce statistical fluctuations a nominal maximum value is calculated as the mean from all voxel > 95%. To find the TS value that yielded an area A best matching the true value, the cross section were auto-contoured in the attenuation corrected slices varying TS in step of 1%, until the area so determined differed by less than 10 mm² versus its known physical value. Multiple regression methods were used to derive an adaptive thresholding algorithm and to test its dependence on different conditions of attenuation and scatter. The errors of scatter and attenuation correction increased with increasing amount of attenuation and scatter in the phantoms. Despite these increasing inaccuracies, PET threshold segmentation algorithms resulted not influenced by the different condition of attenuation and scatter. The test of the hypothesis of coincident regression lines for the three phantoms used

  15. Target detection method by airborne and spaceborne images fusion based on past images

    Science.gov (United States)

    Chen, Shanjing; Kang, Qing; Wang, Zhenggang; Shen, ZhiQiang; Pu, Huan; Han, Hao; Gu, Zhongzheng

    2017-11-01

    To solve the problem that remote sensing target detection method has low utilization rate of past remote sensing data on target area, and can not recognize camouflage target accurately, a target detection method by airborne and spaceborne images fusion based on past images is proposed in this paper. The target area's past of space remote sensing image is taken as background. The airborne and spaceborne remote sensing data is fused and target feature is extracted by the means of airborne and spaceborne images registration, target change feature extraction, background noise suppression and artificial target feature extraction based on real-time aerial optical remote sensing image. Finally, the support vector machine is used to detect and recognize the target on feature fusion data. The experimental results have established that the proposed method combines the target area change feature of airborne and spaceborne remote sensing images with target detection algorithm, and obtains fine detection and recognition effect on camouflage and non-camouflage targets.

  16. Global Calibration of Multiple Cameras Based on Sphere Targets

    Directory of Open Access Journals (Sweden)

    Junhua Sun

    2016-01-01

    Full Text Available Global calibration methods for multi-camera system are critical to the accuracy of vision measurement. Proposed in this paper is such a method based on several groups of sphere targets and a precision auxiliary camera. Each camera to be calibrated observes a group of spheres (at least three, while the auxiliary camera observes all the spheres. The global calibration can be achieved after each camera reconstructs the sphere centers in its field of view. In the process of reconstructing a sphere center, a parameter equation is used to describe the sphere projection model. Theoretical analysis and computer simulation are carried out to analyze the factors that affect the calibration accuracy. Simulation results show that the parameter equation can largely improve the reconstruction accuracy. In the experiments, a two-camera system calibrated by our method is used to measure a distance about 578 mm, and the root mean squared error is within 0.14 mm. Furthermore, the experiments indicate that the method has simple operation and good flexibility, especially for the onsite multiple cameras without common field of view.

  17. Variable epitope library-based vaccines: shooting moving targets.

    Science.gov (United States)

    Pedroza-Roldan, Cesar; Charles-Niño, Claudia; Saavedra, Rafael; Govezensky, Tzipe; Vaca, Luis; Avaniss-Aghajani, Eric; Gevorkian, Goar; Manoutcharian, Karen

    2009-12-01

    While the antigenic variability is the major obstacle for developing vaccines against antigenically variable pathogens (AVPs) and cancer, this issue is not addressed adequately in current vaccine efforts. We developed a novel variable epitope library (VEL)-based vaccine strategy using immunogens carrying a mixture of thousands of variants of a single epitope. In this proof-of-concept study, we used an immunodominant HIV-1-derived CD8+ cytotoxic T-lymphocyte (CTL) epitope as a model antigen to construct immunogens in the form of plasmid DNA and recombinant M13 bacteriophages. We generated combinatorial libraries expressing epitope variants with random amino acid substitutions at 2-5 amino acid positions within the epitope. Mice immunized with these immunogens developed epitope-specific CD8+ IFN-gamma+ T-cell responses that recognized more than 50% of heavily mutated variants of wild-type epitope, as demonstrated in T-cell proliferation assays and FACS analysis. Strikingly, these potent and broad epitope-specific immune responses were long lasting: after 12 months of priming, epitope variants were recognized by CD8+ cells and effector memory T cells were induced. In addition, we showed, for the first time, the inhibition of T-cell responses at the molecular level by immune interference: the mice primed with wild-type epitope and 8 or 12 months later immunized with VELs, were not able to recognize variant epitopes efficiently. These data may give a mechanistic explanation for the failure of recent HIV vaccine trials as well as highlight specific hurdles in current molecular vaccine efforts targeting other important antigenically variable pathogens and diseases. These findings suggest that the VEL-based strategy for immunogen construction can be used as a reliable technological platform for the generation of vaccines against AVPs and cancer, and contribute to better understanding complex host-pathogen interactions.

  18. Semantics based approach for analyzing disease-target associations.

    Science.gov (United States)

    Kaalia, Rama; Ghosh, Indira

    2016-08-01

    A complex disease is caused by heterogeneous biological interactions between genes and their products along with the influence of environmental factors. There have been many attempts for understanding the cause of these diseases using experimental, statistical and computational methods. In the present work the objective is to address the challenge of representation and integration of information from heterogeneous biomedical aspects of a complex disease using semantics based approach. Semantic web technology is used to design Disease Association Ontology (DAO-db) for representation and integration of disease associated information with diabetes as the case study. The functional associations of disease genes are integrated using RDF graphs of DAO-db. Three semantic web based scoring algorithms (PageRank, HITS (Hyperlink Induced Topic Search) and HITS with semantic weights) are used to score the gene nodes on the basis of their functional interactions in the graph. Disease Association Ontology for Diabetes (DAO-db) provides a standard ontology-driven platform for describing genes, proteins, pathways involved in diabetes and for integrating functional associations from various interaction levels (gene-disease, gene-pathway, gene-function, gene-cellular component and protein-protein interactions). An automatic instance loader module is also developed in present work that helps in adding instances to DAO-db on a large scale. Our ontology provides a framework for querying and analyzing the disease associated information in the form of RDF graphs. The above developed methodology is used to predict novel potential targets involved in diabetes disease from the long list of loose (statistically associated) gene-disease associations. Copyright © 2016 Elsevier Inc. All rights reserved.

  19. Polysaccharide-based Noncovalent Assembly for Targeted Delivery of Taxol

    Science.gov (United States)

    Yang, Yang; Zhang, Ying-Ming; Chen, Yong; Chen, Jia-Tong; Liu, Yu

    2016-01-01

    The construction of synthetic straightforward, biocompatible and biodegradable targeted drug delivery system with fluorescent tracking abilities, high anticancer activities and low side effects is still a challenge in the field of biochemistry and material chemistry. In this work, we constructed targeted paclitaxel (Taxol) delivery nanoparticles composed of permethyl-β-cyclodextrin modified hyaluronic acid (HApCD) and porphyrin modified paclitaxel prodrug (PorTaxol), through host-guest and amphiphilic interactions. The obtained nanoparticles (HATXP) were biocompatible and enzymatic biodegradable due to their hydrophilic hyaluronic acid (HA) shell and hydrophobic Taxol core, and exhibited specific targeting internalization into cancer cells via HA receptor mediated endocytosis effects. The cytotoxicity experiments showed that the HATXP exhibited similar anticancer activities to, but much lower side effects than commercial anticancer drug Taxol. The present work would provide a platform for targeted paclitaxel drug delivery and a general protocol for the design of advanced multifunctional nanoscale biomaterials for targeted drug/gene delivery.

  20. Vehicle target detection method based on the average optical flow

    Science.gov (United States)

    Ma, J. Y.; Jie, F. R.; Hu, Y. J.

    2017-07-01

    Moving target detection in image sequence for dynamic scene is an important research topic in the field of computer vision. Block projection and matching are utilized for global motion estimation. Then, the background image is compensated applying the estimated motion parameters so as to stabilize the image sequence. Consequently, background subtraction is employed in the stabilized image sequence to extract moving targets. Finally, divide the difference image into uniform grids and average optical flow is employed for motion analysis. Experiment tests show that the proposed average optical flow method can efficiently extract the vehicle targets from dynamic scene meanwhile decreasing the false alarm.

  1. An active target for the accelerator-based transmutation system

    Energy Technology Data Exchange (ETDEWEB)

    Grebyonkin, K.F. [Institute of Technical Physics, Chelyabinsk (Russian Federation)

    1995-10-01

    Consideration is given to the possibility of radical reduction in power requirements to the proton accelerator of the electronuclear reactor due to neutron multiplication both in the blanket and the target of an active material. The target is supposed to have the fast-neutron spectrum, and the blanket-the thermal one. The blanket and the target are separated by the thermal neutrons absorber, which is responsible for the neutron decoupling of the active target and blanket. Also made are preliminary estimations which illustrate that the realization of the idea under consideration can lead to significant reduction in power requirements to the proton beam and, hence considerably improve economic characteristics of the electronuclear reactor.

  2. Tweet-based Target Market Classification Using Ensemble Method

    Directory of Open Access Journals (Sweden)

    Muhammad Adi Khairul Anshary

    2016-09-01

    Full Text Available Target market classification is aimed at focusing marketing activities on the right targets. Classification of target markets can be done through data mining and by utilizing data from social media, e.g. Twitter. The end result of data mining are learning models that can classify new data. Ensemble methods can improve the accuracy of the models and therefore provide better results. In this study, classification of target markets was conducted on a dataset of 3000 tweets in order to extract features. Classification models were constructed to manipulate the training data using two ensemble methods (bagging and boosting. To investigate the effectiveness of the ensemble methods, this study used the CART (classification and regression tree algorithm for comparison. Three categories of consumer goods (computers, mobile phones and cameras and three categories of sentiments (positive, negative and neutral were classified towards three target-market categories. Machine learning was performed using Weka 3.6.9. The results of the test data showed that the bagging method improved the accuracy of CART with 1.9% (to 85.20%. On the other hand, for sentiment classification, the ensemble methods were not successful in increasing the accuracy of CART. The results of this study may be taken into consideration by companies who approach their customers through social media, especially Twitter.

  3. Identifying problematic drugs based on the characteristics of their targets.

    Science.gov (United States)

    Lopes, Tiago J S; Shoemaker, Jason E; Matsuoka, Yukiko; Kawaoka, Yoshihiro; Kitano, Hiroaki

    2015-01-01

    Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60-70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

  4. Identifying problematic drugs based on the characteristics of their targets

    Directory of Open Access Journals (Sweden)

    Tiago Jose eDa Silva Lopes

    2015-09-01

    Full Text Available Identifying promising compounds during the early stages of drug development is a major challenge for both academia and the pharmaceutical industry. The difficulties are even more pronounced when we consider multi-target pharmacology, where the compounds often target more than one protein, or multiple compounds are used together. Here, we address this problem by using machine learning and network analysis to process sequence and interaction data from human proteins to identify promising compounds. We used this strategy to identify properties that make certain proteins more likely to cause harmful effects when targeted; such proteins usually have domains commonly found throughout the human proteome. Additionally, since currently marketed drugs hit multiple targets simultaneously, we combined the information from individual proteins to devise a score that quantifies the likelihood of a compound being harmful to humans. This approach enabled us to distinguish between approved and problematic drugs with an accuracy of 60%¬–70%. Moreover, our approach can be applied as soon as candidate drugs are available, as demonstrated with predictions for more than 5000 experimental drugs. These resources are available at http://sourceforge.net/projects/psin/.

  5. Efficient Fourier based Algorithm Development for Airborne Moving Target Indication

    NARCIS (Netherlands)

    Lidicky, L.; Hoogeboom, P.

    2009-01-01

    This paper shows how the signal model that is commonly used as a starting point in multi-channel Space Time Adaptive Processing (STAP) for airborne Moving Target Indication (MTI) formally corresponds to a model that can be derived from a bi-static Synthetic Aperture Radar (SAR) model extended for

  6. Structure-based design in the GPCR target space.

    Science.gov (United States)

    Kontoyianni, M; Liu, Z

    2012-01-01

    The G protein-coupled receptors (GPCRs) are membrane proteins that transmit signals via G-protein coupling. They have long been the target of small molecule therapeutics accounting for 30% of the launched drug targets. They are subdivided into several classes, with rhodopsins corresponding to the largest class. Furthermore, a high number of new rhodopsin-like GPCR proteins are included in the druggable genome, thus they are projected to continue being of value to the pharmaceutical and biotechnology sectors. We present a comprehensive review of the structural information pertaining to GPCRs, in light of the most recently deposited crystal structures, along with comparisons of the available to-date structures at different activation states. Finally, computational approaches to GPCR modeling are discussed in conjunction with critical perspectives regarding feasibility and limitations.

  7. Sonar target localization based on spike coded spectrograms

    Directory of Open Access Journals (Sweden)

    Bertrand FONTAINE

    2006-12-01

    Full Text Available Target location is coded into the pattern of spikes that run up the auditory nerve to the bat's brain. Realistic scenes containing multiple, closely spaced, reflectors give rise to complex echo signals consisting of multiple filtered copies of the bat's own vocalisation. Some of this filtering is due to the directivity of the bat’s reception system i.e., the outer ears, and some of it is due to sound absorption and the reflection process. The analysis below concentrates on the conspicuous ridges (notches these filter operations give rise to in the time-frequency representation of the echo as produced by the bat's inner ear. Assuming multiple threshold detecting neurons for each frequency channel it is shown how the distribution of spike times within the generated spike bursts is linked to the presence and characteristics of these notches. A neural network decoding the spike bursts in terms of target location is described.

  8. Electron scattering based on a novel internal target technique: SCRIT

    Energy Technology Data Exchange (ETDEWEB)

    Wakasugi, M.; Emoto, T.; Ito, S.; Wang, S.; Suda, T.; Yano, Y. [RIKEN Nishina Center, Saitama (Japan); Kurita, K.; Ishii, K. [Rikkyo University, Rikkyo (Japan); Tamae, T.; Kuwajima, A. [Tohoku University, Tohoku (Japan); Noda, A.; Shiari, T.; Tongu, H. [Kyoto University, Kyoto (Japan)

    2009-12-15

    A novel technique for forming internal targets, named SCRIT (Self-Confining RI Ion Target), has been developed, which can make electron scattering off short-lived radioactive nuclei possible in an electron storage ring. SCRIT confines the ions of interest by utilizing the ''ion trapping'' phenomenon in the electron storage ring. Approximately 10{sup 7} stable {sup 133}Cs ions were trapped in a three-dimensional configuration along the electron beam axis at an electron beam current of 75 mA. The angular distribution of the electrons scattered from the trapped {sup 133}Cs ions was successfully measured, and a collision luminosity of 10{sup 26}/(cm{sup 2} s) was achieved. (orig.)

  9. Web-based tailored lifestyle programs: exploration of the target group's interests and implications for practice.

    NARCIS (Netherlands)

    Verheijden, M.W.; Jans, M.P.; Hildebrandt, V.H.

    2008-01-01

    An important challenge in Web-based health promotion is to increase the reach of the target audience by taking the target groups' desires into consideration. Data from 505 members of a Dutch Internet panel (representative for Dutch Internet users) were used to asses the target group's interests and

  10. Targeting Customers for Demand Response Based on Big Data

    OpenAIRE

    Kwac, Jungsuk; Rajagopal, Ram

    2014-01-01

    Selecting customers for demand response programs is challenging and existing methodologies are hard to scale and poor in performance. The existing methods were limited by lack of temporal consumption information at the individual customer level. We propose a scalable methodology for demand response targeting utilizing novel data available from smart meters. The approach relies on formulating the problem as a stochastic integer program involving predicted customer responses. A novel approximat...

  11. Exploring Polypharmacology Using a ROCS-Based Target Fishing Approach

    Science.gov (United States)

    2012-01-01

    will interact with the target. Abbreviations: DB number, Drug Bank number; ATC, anatomical therapeutic chemical classification; AMPC, AmpC β- lactamase ...receptor 2; ALR2, aldose reductase 2; AmpC, AmpC β- lactamase ; AUC, area under the curve. Journal of Chemical Information and Modeling Article dx.doi.org...Fluanisone, and (C) Fluoxetine. Abbreviations: ALPHA, α adrenergic receptor; D, dopamine receptor; BETA , β adrenergic receptor; H1, histamine H1 receptor

  12. Host target-based approaches against arboviral diseases.

    Science.gov (United States)

    Rocha, Rebeca Froes; Del Sarto, Juliana Lemos; Marques, Rafael Elias; Costa, Vivian Vasconcelos; Teixeira, Mauro Martins

    2018-02-23

    In the 20th century, socioeconomic and environmental changes facilitated the reintroduction of mosquitoes in developing cities, resulting in the reinsertion of mosquito-borne viral diseases and the dispersal of their causative agents on a worldwide scale. Recurrent outbreaks of arboviral diseases are being reported, even in regions without a previous history of arboviral disease transmission. Of note, arboviral infections represented approximately 30% of all emerging vector-borne diseases in the last decade. Therapeutic strategies against infectious viral diseases include the use of different classes of molecules that act directly on the pathogen and/or act by optimizing the host immune response. Drugs targeting the virus usually provide amelioration of symptoms by suppressing and controlling the infection. However, it is limited by the short-window of effectiveness, ineffectiveness against latent viruses, development of drug-resistant mutants and toxic side effects. Disease may also be a consequence of an excessive, uncontrolled or misplaced inflammatory response, treatments that interfere in host immune response are interesting options and can be used isolated or in combination with virus-targeted therapies. The use of host-targeted therapies requires specific knowledge regarding host immune patterns that may trigger dengue virus (DENV), chikungunya virus (CHIKV) or Zika virus (ZIKV) disease.

  13. Polymer-Based Novel Lung Targeted Delivery Systems.

    Science.gov (United States)

    Elmowafy, Enas; Osman, Rihab; Ishak, Rania A H

    2017-01-01

    Due to its unique features, the respiratory tract had received great attention as a promising non-invasive route for drug administration to achieve both local and systemic effects. Efforts spent to tailor systems able to overcome the lung defence mechanisms and biological barriers are followed in this review. Aerodynamic diameter, morphology, lung deposition and drug release profiles are the main criteria describing the selected new smart lung targeted delivery systems. Novel systems such as nanoparticles, nano-embedded-in microparticles (NEM), small microparticles (MP), large porous particles (LPP), PulmospheresTM and polymeric micelles are used to passively target different areas in the respiratory tract. The most common preparation methods are outlined in the article. Special emphasis was given to the characteristics of the polymers used to fabricate the developed systems. Efforts made to prepare systems using chitosan (CS), alginate (alg), hyaluronic acid (HA), gelatin and albumin as examples of natural polymers and poly lactic-co-glycolic acid (PLGA) and poly(Ɛ-caprolactone) (PCL) as synthetic polymers were compiled. The continuous development and work in the area of lung targeting resulted in the development of engineered smart platforms with the capability to carry small drug molecules, proteins and genes to treat a variety of local and systemic diseases. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  14. Infrared small target detection based on local intensity and gradient properties

    Science.gov (United States)

    Zhang, Hong; Zhang, Lei; Yuan, Ding; Chen, Hao

    2018-03-01

    Infrared small target detection is a challenging task for computer vision due to the factors such as scale variations of the targets and strong clutters. Inspired by the Gaussian-like shape of the small target, we characterize two local properties of the small target from the perspective of intensity and gradient to address this problem. The two properties are that the intensity value of the target pixels is greater than the value of its locally neighboring pixels, and the gradients towards the target center often distribute regularly around the target. First, based on the two properties, the local intensity and gradient (LIG) map is calculated from the original infrared image in order to enhance the targets and suppress clutters. Next, we can obtain the targets conveniently via segmentation from the LIG map. Extensive evaluations on real data demonstrate that the proposed algorithm has satisfactory results in terms of clutter suppression and robustness.

  15. Research on Warehouse Target Localization and Tracking Based on KF and WSN

    Directory of Open Access Journals (Sweden)

    Guang-Rong BIAN

    2014-01-01

    Full Text Available This paper firstly established the model of warehouse targeting and tracking system based on Wireless Sensor Networks (WSN. The principle of Location and tracking is based on the maximum likelihood estimation method of multilateral measurement. According to monitoring motion trajectory of the same unknown target node within a continuous period of time, the motion equation can be established. It can achieve the effective tracking of warehouse target that KF algorithm is applied to carrying out the state estimation of warehouse target motion equation. Simulation results show that, while the warehouse target tracking system state equations are linear, using KF algorithm can obtain satisfactory tracking accuracy.

  16. Research on autonomous identification of airport targets based on Gabor filtering and Radon transform

    Science.gov (United States)

    Yi, Juan; Du, Qingyu; Zhang, Hong jiang; Zhang, Yao lei

    2017-11-01

    Target recognition is a leading key technology in intelligent image processing and application development at present, with the enhancement of computer processing ability, autonomous target recognition algorithm, gradually improve intelligence, and showed good adaptability. Taking the airport target as the research object, analysis the airport layout characteristics, construction of knowledge model, Gabor filter and Radon transform based on the target recognition algorithm of independent design, image processing and feature extraction of the airport, the algorithm was verified, and achieved better recognition results.

  17. Kernel method for clustering based on optimal target vector

    International Nuclear Information System (INIS)

    Angelini, Leonardo; Marinazzo, Daniele; Pellicoro, Mario; Stramaglia, Sebastiano

    2006-01-01

    We introduce Ising models, suitable for dichotomic clustering, with couplings that are (i) both ferro- and anti-ferromagnetic (ii) depending on the whole data-set and not only on pairs of samples. Couplings are determined exploiting the notion of optimal target vector, here introduced, a link between kernel supervised and unsupervised learning. The effectiveness of the method is shown in the case of the well-known iris data-set and in benchmarks of gene expression levels, where it works better than existing methods for dichotomic clustering

  18. Automated Navigation System based on Weapon-Target Assignment

    Directory of Open Access Journals (Sweden)

    Mohammad Khairudin

    2011-12-01

    Full Text Available Operating of weapon on the tank is mostly by manually. It is not desired performance for a critical operation. An automatic control system is required to operate the weapon with the target while maintaining the accuracy. In this paper has designed an automatic weapon control system using object image proccessing. Various an image processing methods used to improve the weapon accuracy to obtain the intended target. The method used in digital image processing is the Camshift motion tracking method. This method is compared with the Lucas Canade motion tracking method. This comparison is conducted to found more precise results between the two methods. Results of object image processing are used to control the direction of the weapon that towards the desired goal. The results show that the implementation of the Lucas Canade motion tracking method using fire simulation tools have been successful. The performance of the Lucas Canade motion tracking methods is better than the CamShift method. Using Lucas Canade method for weapon controller is accordance with the purposes.

  19. Detection algorithm of infrared small target based on improved SUSAN operator

    Science.gov (United States)

    Liu, Xingmiao; Wang, Shicheng; Zhao, Jing

    2010-10-01

    The methods of detecting small moving targets in infrared image sequences that contain moving nuisance objects and background noise is analyzed in this paper. A novel infrared small target detection algorithm based on improved SUSAN operator is put forward. The algorithm selects double templates for the infrared small target detection: one size is greater than the small target point size and another size is equal to the small target point size. First, the algorithm uses the big template to calculate the USAN of each pixel in the image and detect the small target, the edge of the image and isolated noise pixels; Then the algorithm uses the another template to calculate the USAN of pixels detected in the first step and improves the principles of SUSAN algorithm based on the characteristics of the small target so that the algorithm can only detect small targets and don't sensitive to the edge pixels of the image and isolated noise pixels. So the interference of the edge of the image and isolate noise points are removed and the candidate target points can be identified; At last, the target is detected by utilizing the continuity and consistency of target movement. The experimental results indicate that the improved SUSAN detection algorithm can quickly and effectively detect the infrared small targets.

  20. Multiattribute Grey Target Decision Method Based on Soft Set Theory

    Directory of Open Access Journals (Sweden)

    Xia Wang

    2014-01-01

    Full Text Available With respect to the Multiattribute decision-making problems in which the evaluation attribute sets are different and the evaluating values of alternatives are interval grey numbers, a multiattribute grey target decision-making method in which the attribute sets are different was proposed. The concept of grey soft set was defined, and its “AND” operation was assigned by combining the intersection operation of grey number. The expression approach of new grey soft set of attribute sets considering by all decision makers were gained by applying the “AND” operation of grey soft set, and the weights of synthesis attribute were proved. The alternatives were ranked according to the size of distance of bull’s eyes of each alternative under synthetic attribute sets. The green supplier selection was illustrated to demonstrate the effectiveness of proposed model.

  1. 42 CFR 419.30 - Base expenditure target for calendar year 1999.

    Science.gov (United States)

    2010-10-01

    ... 42 Public Health 3 2010-10-01 2010-10-01 false Base expenditure target for calendar year 1999. 419.30 Section 419.30 Public Health CENTERS FOR MEDICARE & MEDICAID SERVICES, DEPARTMENT OF HEALTH AND... Services § 419.30 Base expenditure target for calendar year 1999. (a) CMS estimates the aggregate amount...

  2. Swarm Robots Search for Multiple Targets Based on an Improved Grouping Strategy.

    Science.gov (United States)

    Tang, Qirong; Ding, Lu; Yu, Fangchao; Zhang, Yuan; Li, Yinghao; Tu, Haibo

    2017-03-14

    Swarm robots search for multiple targets in collaboration in unknown environments has been addressed in this paper. An improved grouping strategy based on constriction factors Particle Swarm Optimization is proposed. Robots are grouped under this strategy after several iterations of stochastic movements, which considers the influence range of targets and environmental information they have sensed. The group structure may change dynamically and each group focuses on searching one target. All targets are supposed to be found finally. Obstacle avoidance is considered during the search process. Simulation compared with previous method demonstrates the adaptability, accuracy and efficiency of the proposed strategy in multiple targets searching.

  3. Knowledge-Base Application to Ground Moving Target Detection

    National Research Council Canada - National Science Library

    Adve, R

    2001-01-01

    This report summarizes a multi-year in-house effort to apply knowledge-base control techniques and advanced Space-Time Adaptive Processing algorithms to improve detection performance and false alarm...

  4. Directed energy deflection laboratory measurements of common space based targets

    Science.gov (United States)

    Brashears, Travis; Lubin, Philip; Hughes, Gary B.; Meinhold, Peter; Batliner, Payton; Motta, Caio; Madajian, Jonathan; Mercer, Whitaker; Knowles, Patrick

    2016-09-01

    We report on laboratory studies of the effectiveness of directed energy planetary defense as a part of the DE-STAR (Directed Energy System for Targeting of Asteroids and exploRation) program. DE-STAR and DE-STARLITE are directed energy "stand-off" and "stand-on" programs, respectively. These systems consist of a modular array of kilowatt-class lasers powered by photovoltaics, and are capable of heating a spot on the surface of an asteroid to the point of vaporization. Mass ejection, as a plume of evaporated material, creates a reactionary thrust capable of diverting the asteroid's orbit. In a series of papers, we have developed a theoretical basis and described numerical simulations for determining the thrust produced by material evaporating from the surface of an asteroid. In the DESTAR concept, the asteroid itself is used as the deflection "propellant". This study presents results of experiments designed to measure the thrust created by evaporation from a laser directed energy spot. We constructed a vacuum chamber to simulate space conditions, and installed a torsion balance that holds a common space target sample. The sample is illuminated with a fiber array laser with flux levels up to 60 MW/m2 , which allows us to simulate a mission level flux but on a small scale. We use a separate laser as well as a position sensitive centroid detector to readout the angular motion of the torsion balance and can thus determine the thrust. We compare the measured thrust to the models. Our theoretical models indicate a coupling coefficient well in excess of 100 μN/Woptical, though we assume a more conservative value of 80 μN/Woptical and then degrade this with an optical "encircled energy" efficiency of 0.75 to 60 μN/Woptical in our deflection modeling. Our measurements discussed here yield about 45 μN/Wabsorbed as a reasonable lower limit to the thrust per optical watt absorbed. Results vary depending on the material tested and are limited to measurements of 1 axis, so

  5. SPMK AND GRABCUT BASED TARGET EXTRACTION FROM HIGH RESOLUTION REMOTE SENSING IMAGES

    Directory of Open Access Journals (Sweden)

    W. Cui

    2016-06-01

    Full Text Available Target detection and extraction from high resolution remote sensing images is a basic and wide needed application. In this paper, to improve the efficiency of image interpretation, we propose a detection and segmentation combined method to realize semi-automatic target extraction. We introduce the dense transform color scale invariant feature transform (TC-SIFT descriptor and the histogram of oriented gradients (HOG & HSV descriptor to characterize the spatial structure and color information of the targets. With the k-means cluster method, we get the bag of visual words, and then, we adopt three levels’ spatial pyramid (SP to represent the target patch. After gathering lots of different kinds of target image patches from many high resolution UAV images, and using the TC-SIFT-SP and the multi-scale HOG & HSV feature, we constructed the SVM classifier to detect the target. In this paper, we take buildings as the targets. Experiment results show that the target detection accuracy of buildings can reach to above 90%. Based on the detection results which are a series of rectangle regions of the targets. We select the rectangle regions as candidates for foreground and adopt the GrabCut based and boundary regularized semi-auto interactive segmentation algorithm to get the accurate boundary of the target. Experiment results show its accuracy and efficiency. It can be an effective way for some special targets extraction.

  6. Spmk and Grabcut Based Target Extraction from High Resolution Remote Sensing Images

    Science.gov (United States)

    Cui, Weihong; Wang, Guofeng; Feng, Chenyi; Zheng, Yiwei; Li, Jonathan; Zhang, Yi

    2016-06-01

    Target detection and extraction from high resolution remote sensing images is a basic and wide needed application. In this paper, to improve the efficiency of image interpretation, we propose a detection and segmentation combined method to realize semi-automatic target extraction. We introduce the dense transform color scale invariant feature transform (TC-SIFT) descriptor and the histogram of oriented gradients (HOG) & HSV descriptor to characterize the spatial structure and color information of the targets. With the k-means cluster method, we get the bag of visual words, and then, we adopt three levels' spatial pyramid (SP) to represent the target patch. After gathering lots of different kinds of target image patches from many high resolution UAV images, and using the TC-SIFT-SP and the multi-scale HOG & HSV feature, we constructed the SVM classifier to detect the target. In this paper, we take buildings as the targets. Experiment results show that the target detection accuracy of buildings can reach to above 90%. Based on the detection results which are a series of rectangle regions of the targets. We select the rectangle regions as candidates for foreground and adopt the GrabCut based and boundary regularized semi-auto interactive segmentation algorithm to get the accurate boundary of the target. Experiment results show its accuracy and efficiency. It can be an effective way for some special targets extraction.

  7. Shared Representation of SAR Target and Shadow Based on Multilayer Auto-encoder

    Directory of Open Access Journals (Sweden)

    Sun Zhi-jun

    2013-06-01

    Full Text Available Automatic Target Recognition (ATR of Synthetic Aperture Radar (SAR image is investigated. A SAR feature extraction algorithm based on multilayer auto-encoder is proposed. The method makes use of a probabilistic neural network, Restricted Boltzmann Machine (RBM modeling probability distribution of environment. Through the formation of more expressive multilayer neural network, the deep learning model learns shared representation of the target and its shadow outline reflecting the target shape characteristics. Targets are classified automatically through two recognition models. The experiment results based on the MSTAR verify the effectiveness of proposed algorithm.

  8. Laser-based target tracking using principal component descriptors

    CSIR Research Space (South Africa)

    Burke, Michael G

    2010-11-01

    Full Text Available ]. Here, supervised learning was applied to the problem of building a classifier for the detection of people. Their approach used AdaBoost to create a strong classifier by combining a set of weak classifiers. Their classifier consisted of 14... of classifiers based on the 14 features of [5] in the context of pedestrian detection. A better classifier, which uses AdaBoost to train a classifier using a probabilistic part-based model of geometric laser primitives in conjunction with omnidirectional...

  9. Target-Based Maintenance of Privacy Preserving Association Rules

    Science.gov (United States)

    Ahluwalia, Madhu V.

    2011-01-01

    In the context of association rule mining, the state-of-the-art in privacy preserving data mining provides solutions for categorical and Boolean association rules but not for quantitative association rules. This research fills this gap by describing a method based on discrete wavelet transform (DWT) to protect input data privacy while preserving…

  10. MRI/TRUS fusion software-based targeted biopsy: the new standard of care?

    Science.gov (United States)

    Manfredi, M; Costa Moretti, T B; Emberton, M; Villers, A; Valerio, M

    2015-09-01

    The advent of multiparametric MRI has made it possible to change the way in which prostate biopsy is done, allowing to direct biopsies to suspicious lesions rather than randomly. The subject of this review relates to a computer-assisted strategy, the MRI/US fusion software-based targeted biopsy, and to its performance compared to the other sampling methods. Different devices with different methods to register MR images to live TRUS are currently in use to allow software-based targeted biopsy. Main clinical indications of MRI/US fusion software-based targeted biopsy are re-biopsy in men with persistent suspicious of prostate cancer after first negative standard biopsy and the follow-up of patients under active surveillance. Some studies have compared MRI/US fusion software-based targeted versus standard biopsy. In men at risk with MRI-suspicious lesion, targeted biopsy consistently detects more men with clinically significant disease as compared to standard biopsy; some studies have also shown decreased detection of insignificant disease. Only two studies directly compared MRI/US fusion software-based targeted biopsy with MRI/US fusion visual targeted biopsy, and the diagnostic ability seems to be in favor of the software approach. To date, no study comparing software-based targeted biopsy against in-bore MRI biopsy is available. The new software-based targeted approach seems to have the characteristics to be added in the standard pathway for achieving accurate risk stratification. Once reproducibility and cost-effectiveness will be verified, the actual issue will be to determine whether MRI/TRUS fusion software-based targeted biopsy represents anadd-on test or a replacement to standard TRUS biopsy.

  11. Statistical model based gender prediction for targeted NGS clinical panels

    Directory of Open Access Journals (Sweden)

    Palani Kannan Kandavel

    2017-12-01

    The reference test dataset are being used to test the model. The sensitivity on predicting the gender has been increased from the current “genotype composition in ChrX” based approach. In addition, the prediction score given by the model can be used to evaluate the quality of clinical dataset. The higher prediction score towards its respective gender indicates the higher quality of sequenced data.

  12. Automated Threshold Selection for Template-Based Sonar Target Detection

    Science.gov (United States)

    2017-08-01

    detector performance. An adaptive clutter filter detector has been individually applied to three different sonar images varying in frequency and...like objects, unexploded ordnance, or other man-made debris. The approaches range from as general as possible to very specific. One general approach ...based approach . Each one uses a different model to reproduce three elements which are key to sonar ATR, highlight structure, seabed reverberation

  13. Hardware Accelerators Targeting a Novel Group Based Packet Classification Algorithm

    Directory of Open Access Journals (Sweden)

    O. Ahmed

    2013-01-01

    Full Text Available Packet classification is a ubiquitous and key building block for many critical network devices. However, it remains as one of the main bottlenecks faced when designing fast network devices. In this paper, we propose a novel Group Based Search packet classification Algorithm (GBSA that is scalable, fast, and efficient. GBSA consumes an average of 0.4 megabytes of memory for a 10 k rule set. The worst-case classification time per packet is 2 microseconds, and the preprocessing speed is 3 M rules/second based on an Xeon processor operating at 3.4 GHz. When compared with other state-of-the-art classification techniques, the results showed that GBSA outperforms the competition with respect to speed, memory usage, and processing time. Moreover, GBSA is amenable to implementation in hardware. Three different hardware implementations are also presented in this paper including an Application Specific Instruction Set Processor (ASIP implementation and two pure Register-Transfer Level (RTL implementations based on Impulse-C and Handel-C flows, respectively. Speedups achieved with these hardware accelerators ranged from 9x to 18x compared with a pure software implementation running on an Xeon processor.

  14. Thermally optimized lithium neutron producing target design for accelerator-based BNCT

    International Nuclear Information System (INIS)

    Park Shane; Joo Hyeong Min; Jang Byeong Ill; Jeun, Gyoodong; Kim Jong Kyung; Chai, Jong Seo

    2006-01-01

    In accelerator-based Boron Neutron Capture Therapy (BNCT), 7 Li(p,n) 7 Be reaction is prevalently used as a neutron source. However, lithium has a very low melting point and poor thermal conductivity. Thus lithium target needs an efficient cooling. In this study, ways of increasing proton beam diameter and slanting target are proposed to reduce the heat density of lithium target. Thermal analysis on the lithium target design shows that water cooling is feasible if the proton beam diameter and target slopes are in the available range of the contour plots generated from this study. On the basis of the thermal analysis, the prototype of target system was designed and manufactured. Full-model thermal analysis and temperature measuring experiment were subsequently performed. The calculated temperature distribution coincided with the contour plots and the experimental results. These results will be used in the manufacture of the prototype accelerator-based BNCT facility at Hanyang University. (author)

  15. A Multiobjective Game Approach with a Preferred Target Based on a Leader-Follower Decision Pattern

    Directory of Open Access Journals (Sweden)

    Neng-gang Xie

    2018-01-01

    Full Text Available We propose a multiobjective leader-follower game based on the Stackelberg model, where the designer’s preferred target is taken into account. Here, the preferred target is regarded as a leader and the other targets are regarded as followers. A partition method of strategy subspace is also given. Finally, a real-life example of the multiobjective optimization design of a Chinese arch dam named “Baihetan” is presented to demonstrate the effectiveness of our proposed method.

  16. Correlation-Based Tracking of Multiple Targets With Hierarchical Layered Structure.

    Science.gov (United States)

    Cao, Xianbin; Jiang, Xiaolong; Li, Xiaomei; Yan, Pingkun

    2018-01-01

    Visual target tracking is one of the most important research areas in the field of computer vision. Within this realm, multiple targets tracking (MTT) under complicated scene stands out for its great availability in real life applications, such as urban traffic surveillance and sports video analysis. However, in MTT, main difficulties arise from large variation in target saliency and significant motion heterogeneity, which may result in the failure of tracking weak targets. To tackle this challenge, a novel hierarchical layered tracking structure is proposed to perform tracking sequentially layer-by-layer. Upon this layered structure, we establish an intertarget mutual assistance mechanism on basis of intertarget correlation exploited among targets. The tracking results of a subset of targets can be utilized as additional prior information for tracking other targets. Specifically, a nonlinear motion model as well as a target interaction model basing on the intertarget correlation are proposed to effectively estimate the possible target region-of-interest to facilitate the prediction-based tracking. Moreover, the concept of motion entropy is introduced to quantitatively measure the degree of motion heterogeneity within the tracking scene for layer construction. Compared to other existing methods, extensive experiments demonstrated that the proposed method is capable of achieving higher tracking performance in complicated scenes, where targets are characterized with great heterogeneity.

  17. A new method of small target detection based on neural network

    Science.gov (United States)

    Hu, Jing; Hu, Yongli; Lu, Xinxin

    2018-02-01

    The detection and tracking of moving dim target in infrared image have been an research hotspot for many years. The target in each frame of images only occupies several pixels without any shape and structure information. Moreover, infrared small target is often submerged in complicated background with low signal-to-clutter ratio, making the detection very difficult. Different backgrounds exhibit different statistical properties, making it becomes extremely complex to detect the target. If the threshold segmentation is not reasonable, there may be more noise points in the final detection, which is unfavorable for the detection of the trajectory of the target. Single-frame target detection may not be able to obtain the desired target and cause high false alarm rate. We believe the combination of suspicious target detection spatially in each frame and temporal association for target tracking will increase reliability of tracking dim target. The detection of dim target is mainly divided into two parts, In the first part, we adopt bilateral filtering method in background suppression, after the threshold segmentation, the suspicious target in each frame are extracted, then we use LSTM(long short term memory) neural network to predict coordinates of target of the next frame. It is a brand-new method base on the movement characteristic of the target in sequence images which could respond to the changes in the relationship between past and future values of the values. Simulation results demonstrate proposed algorithm can effectively predict the trajectory of the moving small target and work efficiently and robustly with low false alarm.

  18. Maneuvering Target Detection Based on JRC System in Gaussian and Non-Gaussian Clutter

    Directory of Open Access Journals (Sweden)

    Yu Yao

    2015-01-01

    Full Text Available Aimed at the problem of detecting maneuvering targets in the Gaussian and sea clutter environments and based on the established motion state model, this paper proposed a new scheme that uses a joint radar-communication (JRC system with Kalman filter to accurately detect the target with the generalized likelihood ratio test (GLRT theory and a constant false alarm rate (CFAR based threshold. Also, the theoretical threshold and probability function of GLRT target detection based on CFAR were given. Moreover, target detection probability of the new JRC system in Weibull and K distribution clutter is deduced. In addition to theoretical considerations, simulations and measurement results of the new JRC systems demonstrate excellent detection performance for maneuvering targets in the Weibull and K distribution channel.

  19. Evaluating gaze-based interface tools to facilitate point-and-select tasks with small targets

    DEFF Research Database (Denmark)

    Skovsgaard, Henrik; Mateo, Julio C.; Hansen, John Paulin

    2011-01-01

    Gaze interaction affords hands-free control of computers. Pointing to and selecting small targets using gaze alone is difficult because of the limited accuracy of gaze pointing. This is the first experimental comparison of gaze-based interface tools for small-target (e.g. <12 × 12 pixels) point-a...

  20. The Cost of Event-Based Prospective Memory: Salient Target Events

    Science.gov (United States)

    Smith, Rebekah E.; Hunt, R. Reed; McVay, Jennifer C.; McConnell, Melissa D.

    2007-01-01

    Evidence has begun to accumulate showing that successful performance of event-based prospective memory (PM) comes at a cost to other ongoing activities. The current study builds on previous work by examining the cost associated with PM when the target event is salient. Target salience is among the criteria for automatic retrieval of intentions…

  1. Structure-based drug design approach to target toll-like receptor ...

    African Journals Online (AJOL)

    Figure 1: Structure-based drug design pipeline modified from Grey and Thompson [3]. Table 1: Examples of potential targets whose three-dimensional structures were determined using NMR, x-ray crystallography or homology modeling. Name of target. Technique. Reference. Human transforming growth factor alpha. NMR.

  2. Novel Apigenin Based Small Molecule that Targets Snake Venom Metalloproteases

    Science.gov (United States)

    Anusha, Sebastian; Hemshekhar, Mahadevappa; Chandra Nayaka, Siddaiah; Kemparaju, Kempaiah; Basappa; Girish, Kesturu S.; Rangappa, Kanchugarakoppal S.

    2014-01-01

    The classical antivenom therapy has appreciably reduced snakebite mortality rate and thus is the only savior drug available. Unfortunately, it considerably fails to shield the viper bite complications like hemorrhage, local tissue degradation and necrosis responsible for severe morbidity. Moreover, the therapy is also tagged with limitations including anaphylaxis, serum sickness and poor availability. Over the last decade, snake venom metalloproteases (SVMPs) are reported to be the primary component responsible for hemorrhage and tissue degradation at bitten site. Thus, antivenom inability to offset viper venom-induced local toxicity has been a basis for an insistent search for SVMP inhibitors. Here we report the inhibitory effect of compound 5d, an apigenin based molecule against SVMPs both in silico and in vivo. Several apigenin analogues are synthesized using multicomponent Ugi reactions. Among them, compound 5d effectively abrogated Echis carinatus (EC) venom-induced local hemorrhage, tissue necrosis and myotoxicity in a dose dependant fashion. The histopathological study further conferred effective inhibition of basement membrane degradation, and accumulation of inflammatory leucocytes at the site of EC venom inoculation. The compound also protected EC venom-induced fibrin and fibrinogen degradation. The molecular docking of compound 5d and bothropasin demonstrated the direct interaction of hydroxyl group of compound with Glu146 present in hydrophobic pocket of active site and does not chelate Zn2+. Hence, it is concluded that compound 5d could be a potent agent in viper bite management. PMID:25184206

  3. Expanding the range of 'druggable' targets with natural product-based libraries: an academic perspective.

    Science.gov (United States)

    Bauer, Renato A; Wurst, Jacqueline M; Tan, Derek S

    2010-06-01

    Existing drugs address a relatively narrow range of biological targets. As a result, libraries of drug-like molecules have proven ineffective against a variety of challenging targets, such as protein-protein interactions, nucleic acid complexes, and antibacterial modalities. In contrast, natural products are known to be effective at modulating such targets, and new libraries are being developed based on underrepresented scaffolds and regions of chemical space associated with natural products. This has led to several recent successes in identifying new chemical probes that address these challenging targets. Copyright 2010 Elsevier Ltd. All rights reserved.

  4. In silico structure-based approaches to discover protein-protein interaction-targeting drugs.

    Science.gov (United States)

    Shin, Woong-Hee; Christoffer, Charles W; Kihara, Daisuke

    2017-12-01

    A core concept behind modern drug discovery is finding a small molecule that modulates a function of a target protein. This concept has been successfully applied since the mid-1970s. However, the efficiency of drug discovery is decreasing because the druggable target space in the human proteome is limited. Recently, protein-protein interaction (PPI) has been identified asan emerging target space for drug discovery. PPI plays a pivotal role in biological pathways including diseases. Current human interactome research suggests that the number of PPIs is between 130,000 and 650,000, and only a small number of them have been targeted as drug targets. For traditional drug targets, in silico structure-based methods have been successful in many cases. However, their performance suffers on PPI interfaces because PPI interfaces are different in five major aspects: From a geometric standpoint, they have relatively large interface regions, flat geometry, and the interface surface shape tends to fluctuate upon binding. Also, their interactions are dominated by hydrophobic atoms, which is different from traditional binding-pocket-targeted drugs. Finally, PPI targets usually lack natural molecules that bind to the target PPI interface. Here, we first summarize characteristics of PPI interfaces and their known binders. Then, we will review existing in silico structure-based approaches for discovering small molecules that bind to PPI interfaces. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. A chest-shape target automatic detection method based on Deformable Part Models

    Science.gov (United States)

    Zhang, Mo; Jin, Weiqi; Li, Li

    2016-10-01

    Automatic weapon platform is one of the important research directions at domestic and overseas, it needs to accomplish fast searching for the object to be shot under complex background. Therefore, fast detection for given target is the foundation of further task. Considering that chest-shape target is common target of shoot practice, this paper treats chestshape target as the target and studies target automatic detection method based on Deformable Part Models. The algorithm computes Histograms of Oriented Gradient(HOG) features of the target and trains a model using Latent variable Support Vector Machine(SVM); In this model, target image is divided into several parts then we can obtain foot filter and part filters; Finally, the algorithm detects the target at the HOG features pyramid with method of sliding window. The running time of extracting HOG pyramid with lookup table can be shorten by 36%. The result indicates that this algorithm can detect the chest-shape target in natural environments indoors or outdoors. The true positive rate of detection reaches 76% with many hard samples, and the false positive rate approaches 0. Running on a PC (Intel(R)Core(TM) i5-4200H CPU) with C++ language, the detection time of images with the resolution of 640 × 480 is 2.093s. According to TI company run library about image pyramid and convolution for DM642 and other hardware, our detection algorithm is expected to be implemented on hardware platform, and it has application prospect in actual system.

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

    Science.gov (United States)

    2008-12-01

    LIST OF FIGURES Figure 1. NPS Small UAV, Sig Rascal ................................................................. 2 Figure 2. Conceptual...NPS) to build a Vision Based Target Tracking (VBTT) simulator system in a laboratory environment. Figure 1. NPS Small UAV, Sig Rascal This

  7. Infrared small target detection method based on local threshold attenuation of constant false alarm

    Science.gov (United States)

    Yu, Ke-feng; Shi, Zhi-guang; Lu, Xin-ping

    2016-03-01

    In the infrared small target detection system, CFAR (Constant False Alarm Rate) is a commonly used technology, but in the traditional single frame detection method, detection rate is requested to be improved while the false alarm rate is increasing. This paper proposes a threshold attenuation CFAR detection method based on Gauss distribution. After the preprocessing of infrared images, we came into the designing of CFAR detector based on Gauss distribution. According to the previous frame target location and attenuation of local threshold, the detection rate of the target neighbourhood can be improved to obtain the current target location. The experimental results show that the proposed method can effectively control the threshold, and under the precondition that the background clutter was suppressed by the global low false alarm rate, it can improve the local detection rate and reduce the probability of target loss.

  8. [Research on Multi-Spectral Target Recognition System Based on the Magneto-Optical Modulation].

    Science.gov (United States)

    Yan, Xiao-yan; Qin, Jian-min; Qiao, Ji-pin

    2016-03-01

    The technology of target recognition based on characteristic multi-spectrum has many advantages, such as strong detection capability and discriminating capability of target species. But there are some problems, it requires that you obtain the background spectrum as a priori knowledge, and it requires that the change of background spectrum is small with time. Thereby its application of real-time object recognition is limited in the new environment, or the complex environment. Based on magneto-optical modulation and characteristic multi-spectrum the method is designed, and the target is identified without prior access to the background spectrum. In order to achieve the function of the target information in the one acquisition time for tested, compared to conventional methods in terms of target detection, it's adaptability is better than before on the battlefield, and it is of more practical significance. Meanwhile, the magneto-optical modulator is used to suppress the interference of stray light background, thereby improving the probability of target recognition. Since the magneto-optical modulation provides incremental iterative target spectral information, therefore, even if the unknown background spectrum or background spectrum change is large, it can significantly improve the recognition accuracy of information through an iterative target spectrum. Different test targets back shimmering light intensity and background intensity values were analyzed during experiments, results showed that three targets for linearly polarized reflectance modulation is significantly stronger than the background. And it was of great influence to visible imaging target identification when measured target used camouflage color, but the system of polarization modulation type can still recognize target well. On this basis, the target range within 0.5 km x 2 km multi-wavelength characteristics of the target species were identified. When using three characteristic wavelengths, the

  9. Infrared small target tracking based on sample constrained particle filtering and sparse representation

    Science.gov (United States)

    Zhang, Xiaomin; Ren, Kan; Wan, Minjie; Gu, Guohua; Chen, Qian

    2017-12-01

    Infrared search and track technology for small target plays an important role in infrared warning and guidance. In view of the tacking randomness and uncertainty caused by background clutter and noise interference, a robust tracking method for infrared small target based on sample constrained particle filtering and sparse representation is proposed in this paper. Firstly, to distinguish the normal region and interference region in target sub-blocks, we introduce a binary support vector, and combine it with the target sparse representation model, after which a particle filtering observation model based on sparse reconstruction error differences between sample targets is developed. Secondly, we utilize saliency extraction to obtain the high frequency area in infrared image, and make it as a priori knowledge of the transition probability model to limit the particle filtering sampling process. Lastly, the tracking result is brought about via target state estimation and the Bayesian posteriori probability calculation. Theoretical analyses and experimental results show that our method can enhance the state estimation ability of stochastic particles, improve the sparse representation adaptabilities for infrared small targets, and optimize the tracking accuracy for infrared small moving targets.

  10. DOA Estimation for Underwater Wideband Weak Targets Based on Coherent Signal Subspace and Compressed Sensing

    Directory of Open Access Journals (Sweden)

    Jun Li

    2018-03-01

    Full Text Available Direction of arrival (DOA estimation is the basis for underwater target localization and tracking using towed line array sonar devices. A method of DOA estimation for underwater wideband weak targets based on coherent signal subspace (CSS processing and compressed sensing (CS theory is proposed. Under the CSS processing framework, wideband frequency focusing is accompanied by a two-sided correlation transformation, allowing the DOA of underwater wideband targets to be estimated based on the spatial sparsity of the targets and the compressed sensing reconstruction algorithm. Through analysis and processing of simulation data and marine trial data, it is shown that this method can accomplish the DOA estimation of underwater wideband weak targets. Results also show that this method can considerably improve the spatial spectrum of weak target signals, enhancing the ability to detect them. It can solve the problems of low directional resolution and unreliable weak-target detection in traditional beamforming technology. Compared with the conventional minimum variance distortionless response beamformers (MVDR, this method has many advantages, such as higher directional resolution, wider detection range, fewer required snapshots and more accurate detection for weak targets.

  11. A Side Scan Sonar Image Target Detection Algorithm Based on a Neutrosophic Set and Diffusion Maps

    Directory of Open Access Journals (Sweden)

    Xiao Wang

    2018-02-01

    Full Text Available To accurately achieve side scan sonar (SSS image target detection, a novel target detection algorithm based on a neutrosophic set (NS and diffusion maps (DMs is proposed in this paper. Firstly, the neutrosophic subset images were obtained by transforming the input SSS image into the NS domain. Secondly, the shadowed areas of the SSS image were detected using the single gray value threshold method before the diffusion map was calculated. Lastly, based on the diffusion map, the target areas were detected using the improved target scoring equation defined by the diffusion distance and texture feature. The experiments using SSS images of single clear and unclear targets, with or without shadowed areas, showed that the algorithm accurately detects targets. Experiments using SSS images of multiple targets, with or without shadowed areas, showed that no false or missing detections occurred. The target areas were also accurately detected in SSS images with complex features such as sand wave terrain. The accuracy and effectiveness of the proposed algorithm were assessed.

  12. Information-management data base for fusion-target fabrication processes

    International Nuclear Information System (INIS)

    Reynolds, J.

    1982-01-01

    A computer-based data-management system has been developed to handle data associated with target-fabrication processes including glass microballoon characterization, gas filling, materials coating, and storage locations. The system provides automatic data storage and computation, flexible data-entry procedures, fast access, automated report generation, and secure data transfer. It resides on a CDC CYBER 175 computer and is compatible with the CDC data-base-language Query Update, but is based on custom FORTRAN software interacting directly with the CYBER's file-management system. The described data base maintains detailed, accurate, and readily available records of fusion targets information

  13. Mung bean nuclease treatment increases capture specificity of microdroplet-PCR based targeted DNA enrichment.

    Directory of Open Access Journals (Sweden)

    Zhenming Yu

    Full Text Available Targeted DNA enrichment coupled with next generation sequencing has been increasingly used for interrogation of select sub-genomic regions at high depth of coverage in a cost effective manner. Specificity measured by on-target efficiency is a key performance metric for target enrichment. Non-specific capture leads to off-target reads, resulting in waste of sequencing throughput on irrelevant regions. Microdroplet-PCR allows simultaneous amplification of up to thousands of regions in the genome and is among the most commonly used strategies for target enrichment. Here we show that carryover of single-stranded template genomic DNA from microdroplet-PCR constitutes a major contributing factor for off-target reads in the resultant libraries. Moreover, treatment of microdroplet-PCR enrichment products with a nuclease specific to single-stranded DNA alleviates off-target load and improves enrichment specificity. We propose that nuclease treatment of enrichment products should be incorporated in the workflow of targeted sequencing using microdroplet-PCR for target capture. These findings may have a broad impact on other PCR based applications for which removal of template DNA is beneficial.

  14. Influence networks based on coexpression improve drug target discovery for the development of novel cancer therapeutics

    Science.gov (United States)

    2014-01-01

    Background The demand for novel molecularly targeted drugs will continue to rise as we move forward toward the goal of personalizing cancer treatment to the molecular signature of individual tumors. However, the identification of targets and combinations of targets that can be safely and effectively modulated is one of the greatest challenges facing the drug discovery process. A promising approach is to use biological networks to prioritize targets based on their relative positions to one another, a property that affects their ability to maintain network integrity and propagate information-flow. Here, we introduce influence networks and demonstrate how they can be used to generate influence scores as a network-based metric to rank genes as potential drug targets. Results We use this approach to prioritize genes as drug target candidates in a set of ER + breast tumor samples collected during the course of neoadjuvant treatment with the aromatase inhibitor letrozole. We show that influential genes, those with high influence scores, tend to be essential and include a higher proportion of essential genes than those prioritized based on their position (i.e. hubs or bottlenecks) within the same network. Additionally, we show that influential genes represent novel biologically relevant drug targets for the treatment of ER + breast cancers. Moreover, we demonstrate that gene influence differs between untreated tumors and residual tumors that have adapted to drug treatment. In this way, influence scores capture the context-dependent functions of genes and present the opportunity to design combination treatment strategies that take advantage of the tumor adaptation process. Conclusions Influence networks efficiently find essential genes as promising drug targets and combinations of targets to inform the development of molecularly targeted drugs and their use. PMID:24495353

  15. Comparison of provider and plan-based targeting strategies for disease management.

    Science.gov (United States)

    Annis, Ann M; Holtrop, Jodi Summers; Tao, Min; Chang, Hsiu-Ching; Luo, Zhehui

    2015-05-01

    We aimed to describe and contrast the targeting methods and engagement outcomes for health plan-delivered disease management with those of a provider-delivered care management program. Health plan epidemiologists partnered with university health services researchers to conduct a quasi-experimental, mixed-methods study of a 2-year pilot. We used semi-structured interviews to assess the characteristics of program-targeting strategies, and calculated target and engagement rates from clinical encounter data. Five physician organizations (POs) with 51 participating practices implemented care management. Health plan member lists were sent monthly to the practices to accept patients, and then the practices sent back data reports regarding targeting and engagement in care management. Among patients accepted by the POs, we compared those who were targeted and engaged by POs with those who met health plan targeting criteria. The health plan's targeting process combined claims algorithms and employer group preferences to identify candidates for disease management; on the other hand, several different factors influenced PO practices' targeting approaches, including clinical and personal knowledge of the patients, health assessment information, and availability of disease-relevant programs. Practices targeted a higher percentage of patients for care management than the health plan (38% vs 16%), where only 7% of these patients met the targeting criteria of both. Practices engaged a higher percentage of their targeted patients than the health plan (50% vs 13%). The health plan's claims-driven targeting approach and the clinically based strategies of practices both provide advantages; an optimal model may be to combine the strengths of each approach to maximize benefits in care management.

  16. Prediction of drug-target interactions for drug repositioning only based on genomic expression similarity.

    Directory of Open Access Journals (Sweden)

    Kejian Wang

    Full Text Available Small drug molecules usually bind to multiple protein targets or even unintended off-targets. Such drug promiscuity has often led to unwanted or unexplained drug reactions, resulting in side effects or drug repositioning opportunities. So it is always an important issue in pharmacology to identify potential drug-target interactions (DTI. However, DTI discovery by experiment remains a challenging task, due to high expense of time and resources. Many computational methods are therefore developed to predict DTI with high throughput biological and clinical data. Here, we initiatively demonstrate that the on-target and off-target effects could be characterized by drug-induced in vitro genomic expression changes, e.g. the data in Connectivity Map (CMap. Thus, unknown ligands of a certain target can be found from the compounds showing high gene-expression similarity to the known ligands. Then to clarify the detailed practice of CMap based DTI prediction, we objectively evaluate how well each target is characterized by CMap. The results suggest that (1 some targets are better characterized than others, so the prediction models specific to these well characterized targets would be more accurate and reliable; (2 in some cases, a family of ligands for the same target tend to interact with common off-targets, which may help increase the efficiency of DTI discovery and explain the mechanisms of complicated drug actions. In the present study, CMap expression similarity is proposed as a novel indicator of drug-target interactions. The detailed strategies of improving data quality by decreasing the batch effect and building prediction models are also effectively established. We believe the success in CMap can be further translated into other public and commercial data of genomic expression, thus increasing research productivity towards valid drug repositioning and minimal side effects.

  17. Improved OAM-Based Radar Targets Detection Using Uniform Concentric Circular Arrays

    Directory of Open Access Journals (Sweden)

    Mingtuan Lin

    2016-01-01

    Full Text Available Without any relative moves or beam scanning, the novel Orbital-Angular-Momentum- (OAM- based radar targets detection technique using uniform concentric circular arrays (UCCAs shows the azimuthal estimation ability, which provides new perspective for radar system design. However, the main estimation method, that is, Fast Fourier Transform (FFT, under this scheme suffers from low resolution. As a solution, this paper rebuilds the OAM-based radar targets detection model and introduces the multiple signal classification (MUSIC algorithm to improve the resolution for detecting targets within the main lobes. The spatial smoothing technique is proposed to tackle the coherent problem brought by the proposed model. Analytical study and simulation demonstrate the superresolution estimation capacity the MUSIC algorithm can achieve for detecting targets within the main lobes. The performance of the MUSIC algorithm to detect targets not illuminated by the main lobes is further evaluated. Despite the fact that MUSIC algorithm loses the resolution advantage under this case, its estimation is more robust than that of the FFT method. Overall, the proposed MUSIC algorithm for the OAM-based radar system demonstrates the superresolution ability for detecting targets within the main lobes and good robustness for targets out of the main lobes.

  18. Adaptive detection method of infrared small target based on target-background separation via robust principal component analysis

    Science.gov (United States)

    Wang, Chuanyun; Qin, Shiyin

    2015-03-01

    Motivated by the robust principal component analysis, infrared small target image is regarded as low-rank background matrix corrupted by sparse target and noise matrices, thus a new target-background separation model is designed, subsequently, an adaptive detection method of infrared small target is presented. Firstly, multi-scale transform and patch transform are used to generate an image patch set for infrared small target detection; secondly, target-background separation of each patch is achieved by recovering the low-rank and sparse matrices using adaptive weighting parameter; thirdly, the image reconstruction and fusion are carried out to obtain the entire separated background and target images; finally, the infrared small target detection is realized by threshold segmentation of template matching similarity measurement. In order to validate the performance of the proposed method, three experiments: target-background separation, background clutter suppression and infrared small target detection, are performed over different clutter background with real infrared small targets in single-frame or sequence images. A series of experiment results demonstrate that the proposed method can not only suppress background clutter effectively even if with strong noise interference but also detect targets accurately with low false alarm rate.

  19. Feature Extraction of Underwater Target Signal Using Mel Frequency Cepstrum Coefficients Based on Acoustic Vector Sensor

    Directory of Open Access Journals (Sweden)

    Lanyue Zhang

    2016-01-01

    Full Text Available Feature extraction method using Mel frequency cepstrum coefficients (MFCC based on acoustic vector sensor is researched in the paper. Signals of pressure are simulated as well as particle velocity of underwater target, and the features of underwater target using MFCC are extracted to verify the feasibility of the method. The experiment of feature extraction of two kinds of underwater targets is carried out, and these underwater targets are classified and recognized by Backpropagation (BP neural network using fusion of multi-information. Results of the research show that MFCC, first-order differential MFCC, and second-order differential MFCC features could be used as effective features to recognize those underwater targets and the recognition rate, which using the particle velocity signal is higher than that using the pressure signal, could be improved by using fusion features.

  20. Multi-target Particle Filter Tracking Algorithm Based on Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Liu Hong-Xia

    2014-05-01

    Full Text Available In order to improve the multi-target tracking efficiency for wireless sensor networks and solve the problem of data transmission, analyzed existing particle filter tracking algorithm, ensure that one of the core technology for wireless sensor network performance. In this paper, from the basic theory of target tracking, in-depth analysis on the basis of the principle of particle filter, based on dynamic clustering, proposed the multi-target Kalman particle filter (MEPF algorithm, through the expansion of Calman filter (EKF to generate the proposal distribution, a reduction in the required number of particles to improve the particle filter accuracy at the same time, reduce the computational complexity of target tracking algorithm, thus reducing the energy consumption. Application results show that the MEPF in the proposed algorithm can achieve better tracking of target tracking and forecasting, in a small number of particles still has good tracking accuracy.

  1. Bag-of-visual-words based feature extraction for SAR target classification

    Science.gov (United States)

    Amrani, Moussa; Chaib, Souleyman; Omara, Ibrahim; Jiang, Feng

    2017-07-01

    Feature extraction plays a key role in the classification performance of synthetic aperture radar automatic target recognition (SAR-ATR). It is very crucial to choose appropriate features to train a classifier, which is prerequisite. Inspired by the great success of Bag-of-Visual-Words (BoVW), we address the problem of feature extraction by proposing a novel feature extraction method for SAR target classification. First, Gabor based features are adopted to extract features from the training SAR images. Second, a discriminative codebook is generated using K-means clustering algorithm. Third, after feature encoding by computing the closest Euclidian distance, the targets are represented by new robust bag of features. Finally, for target classification, support vector machine (SVM) is used as a baseline classifier. Experiments on Moving and Stationary Target Acquisition and Recognition (MSTAR) public release dataset are conducted, and the classification accuracy and time complexity results demonstrate that the proposed method outperforms the state-of-the-art methods.

  2. Maximum Likelihood-Based Methods for Target Velocity Estimation with Distributed MIMO Radar

    Directory of Open Access Journals (Sweden)

    Zhenxin Cao

    2018-02-01

    Full Text Available The estimation problem for target velocity is addressed in this in the scenario with a distributed multi-input multi-out (MIMO radar system. A maximum likelihood (ML-based estimation method is derived with the knowledge of target position. Then, in the scenario without the knowledge of target position, an iterative method is proposed to estimate the target velocity by updating the position information iteratively. Moreover, the Carmér-Rao Lower Bounds (CRLBs for both scenarios are derived, and the performance degradation of velocity estimation without the position information is also expressed. Simulation results show that the proposed estimation methods can approach the CRLBs, and the velocity estimation performance can be further improved by increasing either the number of radar antennas or the information accuracy of the target position. Furthermore, compared with the existing methods, a better estimation performance can be achieved.

  3. Research on regional intrusion prevention and control system based on target tracking

    Science.gov (United States)

    Liu, Yanfei; Wang, Jieling; Jiang, Ke; He, Yanhui; Wu, Zhilin

    2017-08-01

    In view of the fact that China’s border is very long and the border prevention and control measures are single, we designed a regional intrusion prevention and control system which based on target-tracking. The system consists of four parts: solar panel, radar, electro-optical equipment, unmanned aerial vehicle and intelligent tracking platform. The solar panel provides independent power for the entire system. The radar detects the target in real time and realizes the high precision positioning of suspicious targets, then through the linkage of electro-optical equipment, it can achieve full-time automatic precise tracking of targets. When the target appears within the range of detection, the drone will be launched to continue the tracking. The system is mainly to realize the full time, full coverage, whole process integration and active realtime control of the border area.

  4. Multiple Maneuvering Target Tracking by Improved Particle Filter Based on Multiscan JPDA

    Directory of Open Access Journals (Sweden)

    Jing Liu

    2012-01-01

    Full Text Available The multiple maneuvering target tracking algorithm based on a particle filter is addressed. The equivalent-noise approach is adopted, which uses a simple dynamic model consisting of target state and equivalent noise which accounts for the combined effects of the process noise and maneuvers. The equivalent-noise approach converts the problem of maneuvering target tracking to that of state estimation in the presence of nonstationary process noise with unknown statistics. A novel method for identifying the nonstationary process noise is proposed in the particle filter framework. Furthermore, a particle filter based multiscan Joint Probability Data Association (JPDA filter is proposed to deal with the data association problem in a multiple maneuvering target tracking. In the proposed multiscan JPDA algorithm, the distributions of interest are the marginal filtering distributions for each of the targets, and these distributions are approximated with particles. The multiscan JPDA algorithm examines the joint association events in a multiscan sliding window and calculates the marginal posterior probability based on the multiscan joint association events. The proposed algorithm is illustrated via an example involving the tracking of two highly maneuvering, at times closely spaced and crossed, targets, based on resolved measurements.

  5. Beyond the Sparsity-Based Target Detector: A Hybrid Sparsity and Statistics Based Detector for Hyperspectral Images.

    Science.gov (United States)

    Du, Bo; Zhang, Yuxiang; Zhang, Liangpei; Tao, Dacheng

    2016-08-18

    Hyperspectral images provide great potential for target detection, however, new challenges are also introduced for hyperspectral target detection, resulting that hyperspectral target detection should be treated as a new problem and modeled differently. Many classical detectors are proposed based on the linear mixing model and the sparsity model. However, the former type of model cannot deal well with spectral variability in limited endmembers, and the latter type of model usually treats the target detection as a simple classification problem and pays less attention to the low target probability. In this case, can we find an efficient way to utilize both the high-dimension features behind hyperspectral images and the limited target information to extract small targets? This paper proposes a novel sparsitybased detector named the hybrid sparsity and statistics detector (HSSD) for target detection in hyperspectral imagery, which can effectively deal with the above two problems. The proposed algorithm designs a hypothesis-specific dictionary based on the prior hypotheses for the test pixel, which can avoid the imbalanced number of training samples for a class-specific dictionary. Then, a purification process is employed for the background training samples in order to construct an effective competition between the two hypotheses. Next, a sparse representation based binary hypothesis model merged with additive Gaussian noise is proposed to represent the image. Finally, a generalized likelihood ratio test is performed to obtain a more robust detection decision than the reconstruction residual based detection methods. Extensive experimental results with three hyperspectral datasets confirm that the proposed HSSD algorithm clearly outperforms the stateof- the-art target detectors.

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

    Science.gov (United States)

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

    2017-10-01

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

  7. Moving target detection based on temporal-spatial information fusion for infrared image sequences

    Science.gov (United States)

    Toing, Wu-qin; Xiong, Jin-yu; Zeng, An-jun; Wu, Xiao-ping; Xu, Hao-peng

    2009-07-01

    Moving target detection and localization is one of the most fundamental tasks in visual surveillance. In this paper, through analyzing the advantages and disadvantages of the traditional approaches about moving target detection, a novel approach based on temporal-spatial information fusion is proposed for moving target detection. The proposed method combines the spatial feature in single frame and the temporal properties within multiple frames of an image sequence of moving target. First, the method uses the spatial image segmentation for target separation from background and uses the local temporal variance for extracting targets and wiping off the trail artifact. Second, the logical "and" operator is used to fuse the temporal and spatial information. In the end, to the fusion image sequence, the morphological filtering and blob analysis are used to acquire exact moving target. The algorithm not only requires minimal computation and memory but also quickly adapts to the change of background and environment. Comparing with other methods, such as the KDE, the Mixture of K Gaussians, etc., the simulation results show the proposed method has better validity and higher adaptive for moving target detection, especially in infrared image sequences with complex illumination change, noise change, and so on.

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

    Science.gov (United States)

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

    2018-03-27

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

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

    Directory of Open Access Journals (Sweden)

    Sohyun Kim

    2018-03-01

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

  10. A calibration method based on virtual large planar target for cameras with large FOV

    Science.gov (United States)

    Yu, Lei; Han, Yangyang; Nie, Hong; Ou, Qiaofeng; Xiong, Bangshu

    2018-02-01

    In order to obtain high precision in camera calibration, a target should be large enough to cover the whole field of view (FOV). For cameras with large FOV, using a small target will seriously reduce the precision of calibration. However, using a large target causes many difficulties in making, carrying and employing the large target. In order to solve this problem, a calibration method based on the virtual large planar target (VLPT), which is virtually constructed with multiple small targets (STs), is proposed for cameras with large FOV. In the VLPT-based calibration method, first, the positions and directions of STs are changed several times to obtain a number of calibration images. Secondly, the VLPT of each calibration image is created by finding the virtual point corresponding to the feature points of the STs. Finally, intrinsic and extrinsic parameters of the camera are calculated by using the VLPTs. Experiment results show that the proposed method can not only achieve the similar calibration precision as those employing a large target, but also have good stability in the whole measurement area. Thus, the difficulties to accurately calibrate cameras with large FOV can be perfectly tackled by the proposed method with good operability.

  11. Through-Wall Multiple Targets Vital Signs Tracking Based on VMD Algorithm

    Directory of Open Access Journals (Sweden)

    Jiaming Yan

    2016-08-01

    Full Text Available Targets located at the same distance are easily neglected in most through-wall multiple targets detecting applications which use the single-input single-output (SISO ultra-wideband (UWB radar system. In this paper, a novel multiple targets vital signs tracking algorithm for through-wall detection using SISO UWB radar has been proposed. Taking advantage of the high-resolution decomposition of the Variational Mode Decomposition (VMD based algorithm, the respiration signals of different targets can be decomposed into different sub-signals, and then, we can track the time-varying respiration signals accurately when human targets located in the same distance. Intensive evaluation has been conducted to show the effectiveness of our scheme with a 0.15 m thick concrete brick wall. Constant, piecewise-constant and time-varying vital signs could be separated and tracked successfully with the proposed VMD based algorithm for two targets, even up to three targets. For the multiple targets’ vital signs tracking issues like urban search and rescue missions, our algorithm has superior capability in most detection applications.

  12. Automatic Target Recognition in Synthetic Aperture Sonar Images Based on Geometrical Feature Extraction

    Directory of Open Access Journals (Sweden)

    J. Del Rio Vera

    2009-01-01

    Full Text Available This paper presents a new supervised classification approach for automated target recognition (ATR in SAS images. The recognition procedure starts with a novel segmentation stage based on the Hilbert transform. A number of geometrical features are then extracted and used to classify observed objects against a previously compiled database of target and non-target features. The proposed approach has been tested on a set of 1528 simulated images created by the NURC SIGMAS sonar model, achieving up to 95% classification accuracy.

  13. Exploring Cellular Targets of Vanillin Based on Morphological Changes of Saccharomyces cerevisiae

    OpenAIRE

    Suga, Yohei

    2011-01-01

    Vanillin is one of the major phenolic compounds degraded from lignin. It is considered as a problematic byproduct of bioethanol production from lignocelluloses since it inhibits yeast growth and fermentation. However, detailed inhibitory mechanisms of vanillin are still unknown. In this study, I investigated intercellular targets of vanillin based on the image profiling method to infer the drug targets developed recently (Ohnuki et al., 2010). Using this method, I revealed that the morphology...

  14. Aptamer and nanotechnology- based approaches for active targeted delivery of anti-tuberculosis drugs

    CSIR Research Space (South Africa)

    Ramalapa, B

    2012-10-01

    Full Text Available and Nanotechnology- based Approaches for Active Targeted Delivery of Anti-Tuberculosis Drugs Presented by : Bathabile Ramalapa CSIR Emerging Researcher Symposium 10 0ctober 2012 Outline ? Background: Challenges in the current TB treatment ? Proposed Solution...-expressed by TB infected macrophages Aptamers: RNA/DNA that bind to a specific target molecule ?Enhance drug efficiency at site of infection ?Reduce systemic toxicity Aptamer Synthesis: SELEX Method ? CSIR 2012 www.csir.co.za Partitioning...

  15. Comparing methods of targeting obesity interventions in populations: An agent-based simulation.

    Science.gov (United States)

    Beheshti, Rahmatollah; Jalalpour, Mehdi; Glass, Thomas A

    2017-12-01

    Social networks as well as neighborhood environments have been shown to effect obesity-related behaviors including energy intake and physical activity. Accordingly, harnessing social networks to improve targeting of obesity interventions may be promising to the extent this leads to social multiplier effects and wider diffusion of intervention impact on populations. However, the literature evaluating network-based interventions has been inconsistent. Computational methods like agent-based models (ABM) provide researchers with tools to experiment in a simulated environment. We develop an ABM to compare conventional targeting methods (random selection, based on individual obesity risk, and vulnerable areas) with network-based targeting methods. We adapt a previously published and validated model of network diffusion of obesity-related behavior. We then build social networks among agents using a more realistic approach. We calibrate our model first against national-level data. Our results show that network-based targeting may lead to greater population impact. We also present a new targeting method that outperforms other methods in terms of intervention effectiveness at the population level.

  16. Non-target adjacent stimuli classification improves performance of classical ERP-based brain computer interface

    Science.gov (United States)

    Ceballos, G. A.; Hernández, L. F.

    2015-04-01

    Objective. The classical ERP-based speller, or P300 Speller, is one of the most commonly used paradigms in the field of Brain Computer Interfaces (BCI). Several alterations to the visual stimuli presentation system have been developed to avoid unfavorable effects elicited by adjacent stimuli. However, there has been little, if any, regard to useful information contained in responses to adjacent stimuli about spatial location of target symbols. This paper aims to demonstrate that combining the classification of non-target adjacent stimuli with standard classification (target versus non-target) significantly improves classical ERP-based speller efficiency. Approach. Four SWLDA classifiers were trained and combined with the standard classifier: the lower row, upper row, right column and left column classifiers. This new feature extraction procedure and the classification method were carried out on three open databases: the UAM P300 database (Universidad Autonoma Metropolitana, Mexico), BCI competition II (dataset IIb) and BCI competition III (dataset II). Main results. The inclusion of the classification of non-target adjacent stimuli improves target classification in the classical row/column paradigm. A gain in mean single trial classification of 9.6% and an overall improvement of 25% in simulated spelling speed was achieved. Significance. We have provided further evidence that the ERPs produced by adjacent stimuli present discriminable features, which could provide additional information about the spatial location of intended symbols. This work promotes the searching of information on the peripheral stimulation responses to improve the performance of emerging visual ERP-based spellers.

  17. Infrared dim moving target tracking via sparsity-based discriminative classifier and convolutional network

    Science.gov (United States)

    Qian, Kun; Zhou, Huixin; Wang, Bingjian; Song, Shangzhen; Zhao, Dong

    2017-11-01

    Infrared dim and small target tracking is a great challenging task. The main challenge for target tracking is to account for appearance change of an object, which submerges in the cluttered background. An efficient appearance model that exploits both the global template and local representation over infrared image sequences is constructed for dim moving target tracking. A Sparsity-based Discriminative Classifier (SDC) and a Convolutional Network-based Generative Model (CNGM) are combined with a prior model. In the SDC model, a sparse representation-based algorithm is adopted to calculate the confidence value that assigns more weights to target templates than negative background templates. In the CNGM model, simple cell feature maps are obtained by calculating the convolution between target templates and fixed filters, which are extracted from the target region at the first frame. These maps measure similarities between each filter and local intensity patterns across the target template, therefore encoding its local structural information. Then, all the maps form a representation, preserving the inner geometric layout of a candidate template. Furthermore, the fixed target template set is processed via an efficient prior model. The same operation is applied to candidate templates in the CNGM model. The online update scheme not only accounts for appearance variations but also alleviates the migration problem. At last, collaborative confidence values of particles are utilized to generate particles' importance weights. Experiments on various infrared sequences have validated the tracking capability of the presented algorithm. Experimental results show that this algorithm runs in real-time and provides a higher accuracy than state of the art algorithms.

  18. Adaptive target binarization method based on a dual-camera system

    Science.gov (United States)

    Lei, Jing; Zhang, Ping; Xu, Jiangtao; Gao, Zhiyuan; Gao, Jing

    2018-01-01

    An adaptive target binarization method based on a dual-camera system that contains two dynamic vision sensors was proposed. First, a preprocessing procedure of denoising is introduced to remove the noise events generated by the sensors. Then, the complete edge of the target is retrieved and represented by events based on an event mosaicking method. Third, the region of the target is confirmed by an event-to-event method. Finally, a postprocessing procedure of image open and close operations of morphology methods is adopted to remove the artifacts caused by event-to-event mismatching. The proposed binarization method has been extensively tested on numerous degraded images with nonuniform illumination, low contrast, noise, or light spots and successfully compared with other well-known binarization methods. The experimental results, which are based on visual and misclassification error criteria, show that the proposed method performs well and has better robustness on the binarization of degraded images.

  19. Polysaccharide-based micro/nanocarriers for oral colon-targeted drug delivery.

    Science.gov (United States)

    Zhang, Lin; Sang, Yuan; Feng, Jing; Li, Zhaoming; Zhao, Aili

    2016-08-01

    Oral colon-targeted drug delivery has attracted many researchers because of its distinct advantages of increasing the bioavailability of the drug at the target site and reducing the side effects. Polysaccharides that are precisely activated by the physiological environment of the colon hold greater promise for colon targeting. Considerable research efforts have been directed towards developing polysaccharide-based micro/nanocarriers. Types of polysaccharides for colon targeting and in vitro/in vivo assessments of polysaccharide-based carriers for oral colon-targeted drug delivery are summarised. Polysaccharide-based microspheres have gained increased importance not just for the delivery of the drugs for the treatment of local diseases associated with the colon (colon cancer, inflammatory bowel disease (IBD), amoebiasis and irritable bowel syndrome (IBS)), but also for it's potential for the delivery of anti-rheumatoid arthritis and anti-chronic stable angina drugs. Besides, Polysaccharide-based micro/nanocarriers such as microbeads, microcapsules, microparticles, nanoparticles, nanogels and nanospheres are also introduced in this review.

  20. High-Speed Target Identification System Based on the Plume’s Spectral Distribution

    Directory of Open Access Journals (Sweden)

    Wenjie Lang

    2015-01-01

    Full Text Available In order to recognize the target of high speed quickly and accurately, an identification system was designed based on analysis of the distribution characteristics of the plume spectrum. In the system, the target was aligned with visible light tracking module, and the spectral analysis of the target’s plume radiation was achieved by interference module. The distinguishing factor recognition algorithm was designed on basis of ratio of multifeature band peaks and valley mean values. Effective recognition of the high speed moving target could be achieved after partition of the active region and the influence of target motion on spectral acquisition was analyzed. In the experiment the small rocket combustion was used as the target. The spectral detection experiment was conducted at different speeds 2.0 km away from the detection system. Experimental results showed that spectral distribution had significant spectral offset in the same sampling period for the target with different speeds, but the spectral distribution was basically consistent. Through calculation of the inclusion relationship between distinguishing factor and distinction interval of the peak value and the valley value at the corresponding wave-bands, effective identification of target could be achieved.

  1. Ultrasound Imaging Based on Molecular Targeting for Quantitative Evaluation of Hepatic Ischemia-Reperfusion Injury.

    Science.gov (United States)

    Qiu, C; Yin, T; Zhang, Y; Lian, Y; You, Y; Wang, K; Zheng, R; Shuai, X

    2017-12-01

    The aim of the present study was to quantitatively diagnose and monitor the therapy response of hepatic ischemia-reperfusion injury (IRI) with the use of targeted ultrasound (US) imaging. Targeted microbubbles (MBs) were fabricated, and the binding of intracellular adhesion molecule 1 (ICAM-1) antibodies to MBs was observed. To establish a quantitative method based on targeted US imaging, contrast-enhanced US was applied for IRI rats. After andrographolide treatment, the IRI rats were subjected to the quantitative targeted US imaging for a therapeutic effect. Effective binding of ICAM-1 antibodies to MBs was observed. According to the quantitative targeted US imaging, the ICAM-1 normalized intensity difference (NID) in the IRI rats (38.74 ± 15.08%) was significantly higher than that in the control rats (10.08 ± 2.52%, p = 0.048). Further, different degrees of IRI (mild IRI, moderate to severe IRI) were distinguished by the use of the NID (37.14 ± 2.14%, 22.34 ± 1.08%, p = 0.002). Analysis of mRNA expression demonstrated the accuracy of analyzing the NID by using quantitative targeted US imaging (R 2  = 0.7434, p quantitative targeted US imaging method for the diagnosis and therapeutic monitoring of IRI. © 2017 The American Society of Transplantation and the American Society of Transplant Surgeons.

  2. Cluster-based Dynamic Energy Management for Collaborative Target Tracking in Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Dao-Wei Bi

    2007-07-01

    Full Text Available A primary criterion of wireless sensor network is energy efficiency. Focused onthe energy problem of target tracking in wireless sensor networks, this paper proposes acluster-based dynamic energy management mechanism. Target tracking problem isformulated by the multi-sensor detection model as well as energy consumption model. Adistributed adaptive clustering approach is investigated to form a reasonable routingframework which has uniform cluster head distribution. Dijkstra’s algorithm is utilized toobtain optimal intra-cluster routing. Target position is predicted by particle filter. Thepredicted target position is adopted to estimate the idle interval of sensor nodes. Hence,dynamic awakening approach is exploited to prolong sleep time of sensor nodes so that theoperation energy consumption of wireless sensor network can be reduced. The sensornodes around the target wake up on time and act as sensing candidates. With the candidatesensor nodes and predicted target position, the optimal sensor node selection is considered.Binary particle swarm optimization is proposed to minimize the total energy consumptionduring collaborative sensing and data reporting. Experimental results verify that theproposed clustering approach establishes a low-energy communication structure while theenergy efficiency of wireless sensor networks is enhanced by cluster-based dynamic energymanagement.

  3. Structure-guided, target-based drug discovery - exploiting genome information from HIV to mycobacterial infections.

    Science.gov (United States)

    Malhotra, Sony; Thomas, Sherine E; Ochoa Montano, Bernardo; Blundell, Tom L

    The use of protein crystallography in structure-guided drug discovery allows identification of potential inhibitor-binding sites and optimisation of interactions of hits and lead compounds with a target protein. An early example of this approach was the use of the structure of HIV protease in designing AIDS antivirals. More recently, use of structure-guided design with fragment-based drug discovery, which reduces the size of screening libraries by decreasing complexity, has improved ligand efficiency in drug design. Here, we discuss the use of structure-guided target identification and lead optimisation using fragment-based approaches in the development of new antimicrobials for mycobacterial infections.

  4. Land-Based Mitigation Strategies under the Mid-Term Carbon Reduction Targets in Indonesia

    Directory of Open Access Journals (Sweden)

    Tomoko Hasegawa

    2016-12-01

    Full Text Available We investigated the key mitigation options for achieving the mid-term target for carbon emission reduction in Indonesia. A computable general equilibrium model coupled with a land-based mitigation technology model was used to evaluate specific mitigation options within the whole economic framework. The results revealed three primary findings: (1 If no climate policy were implemented, Indonesia’s total greenhouse gas emissions would reach 3.0 GtCO2eq by 2030; (2 To reduce carbon emissions to meet the latest Intended Nationally-Determined Contributions (INDC target, ~58% of total reductions should come from the agriculture, forestry and other land use sectors by implementing forest protection, afforestation and plantation efforts; (3 A higher carbon price in 2020 suggests that meeting the 2020 target would be economically challenging, whereas the INDC target for 2030 would be more economically realistic in Indonesia.

  5. Impact Time Guidance Law Considering Autopilot Dynamics Based on Variable Coefficients Strategy for Maneuvering Target

    Directory of Open Access Journals (Sweden)

    Wei Shang

    2015-01-01

    Full Text Available This paper investigates the terminal guidance problem for the missile intercepting a maneuvering target with impact time constraint. An impact time guidance law based on finite time convergence control theory is developed regarding the target motion as an unknown disturbance. To further improve the performance of the guidance law, an autopilot dynamics which is considered as a first-order lag is taken into consideration. In the proposed method, the coefficients change with the relative distance between missile and target. This variable coefficient strategy ensures that the missile impacts the target at the desired time with little final miss distance. Then it is proved that states of the guidance system converge to sliding mode in finite time under the proposed guidance law. Numerical simulations are presented to demonstrate the effectiveness of the impact time guidance law with autopilot dynamics (ITGAD.

  6. Research on Ground Motion Metal Target Based on Rocket Projectile by Using Millimeter Wave Radiometer Technology

    Directory of Open Access Journals (Sweden)

    Zhang Dongyang

    2014-06-01

    Full Text Available How to detect the ground motion metal target effectively is an important guarantee for precision strike in the process of Rocket Projectile flight. Accordingly and in view of the millimeter- wave radiation characteristic of the ground motion metal target, a mathematical model was established based on Rocket Projectile about millimeter-wave detection to the ground motion metal target. Through changing various parameters in the process of Rocket Projectile flight, the detection model was studied by simulation. The parameters variation and effective range of millimeter wave radiometer were obtained in the process of rotation and horizontal flight. So a certain theoretical basis was formed for the precision strike to the ground motion metal target.

  7. An infrared small target detection method based on nonnegative matrix factorization and compressed sensing

    Science.gov (United States)

    Chen, Qiwei; Wang, Yiming

    2017-07-01

    According to the low rank property of the background and the sparse features of the target in infrared image, a novel infrared small target detection method based on the nonnegative matrix factorization (NMF) and compressed sensing technology was presented in this paper. This method trained background model through NMF, and then sampled the infrared image sequences directly using the block compressed sensing technology. Through the alternating direction method of multipliers (ADMM), the infrared small target was extracted and the background was recovered from the image. At the same time, the background was updated by the update algorithm, to adapt to the changes in the background. The simulation results show that the proposed method can detect the infrared target precisely and efficiently.

  8. Implementation Of Vision-Based Landing Target Detection For VTOL UAV Using Raspberry Pi

    Directory of Open Access Journals (Sweden)

    Ei Ei Nyein

    2017-04-01

    Full Text Available This paper presents development and implementation of a real-time vision-based landing system for VTOL UAV. We use vision for precise target detection and recognition. A UAV is equipped with the onboard raspberry pi camera to take images and raspberry pi platform to operate the image processing techniques. Today image processing is used for various applications in this paper it is used for landing target extraction. And vision system is also used for take-off and landing function in VTOL UAV. Our landing target design is used as the helipad H shape. Firstly the image is captured to detect the target by the onboard camera. Next the capture image is operated in the onboard processor. Finally the alert sound signal is sent to the remote control RC for landing VTOL UAV. The information obtained from vision system is used to navigate a safe landing. The experimental results from real tests are presented.

  9. An Improved Compressive Sensing and Received Signal Strength-Based Target Localization Algorithm with Unknown Target Population for Wireless Local Area Networks

    Directory of Open Access Journals (Sweden)

    Jun Yan

    2017-05-01

    Full Text Available In this paper a two-phase compressive sensing (CS and received signal strength (RSS-based target localization approach is proposed to improve position accuracy by dealing with the unknown target population and the effect of grid dimensions on position error. In the coarse localization phase, by formulating target localization as a sparse signal recovery problem, grids with recovery vector components greater than a threshold are chosen as the candidate target grids. In the fine localization phase, by partitioning each candidate grid, the target position in a grid is iteratively refined by using the minimum residual error rule and the least-squares technique. When all the candidate target grids are iteratively partitioned and the measurement matrix is updated, the recovery vector is re-estimated. Threshold-based detection is employed again to determine the target grids and hence the target population. As a consequence, both the target population and the position estimation accuracy can be significantly improved. Simulation results demonstrate that the proposed approach achieves the best accuracy among all the algorithms compared.

  10. Exploring the potential of a structural alphabet-based tool for mining multiple target conformations and target flexibility insight.

    Directory of Open Access Journals (Sweden)

    Leslie Regad

    Full Text Available Protein flexibility is often implied in binding with different partners and is essential for protein function. The growing number of macromolecular structures in the Protein Data Bank entries and their redundancy has become a major source of structural knowledge of the protein universe. The analysis of structural variability through available redundant structures of a target, called multiple target conformations (MTC, obtained using experimental or modeling methods and under different biological conditions or different sources is one way to explore protein flexibility. This analysis is essential to improve the understanding of various mechanisms associated with protein target function and flexibility. In this study, we explored structural variability of three biological targets by analyzing different MTC sets associated with these targets. To facilitate the study of these MTC sets, we have developed an efficient tool, SA-conf, dedicated to capturing and linking the amino acid and local structure variability and analyzing the target structural variability space. The advantage of SA-conf is that it could be applied to divers sets composed of MTCs available in the PDB obtained using NMR and crystallography or homology models. This tool could also be applied to analyze MTC sets obtained by dynamics approaches. Our results showed that SA-conf tool is effective to quantify the structural variability of a MTC set and to localize the structural variable positions and regions of the target. By selecting adapted MTC subsets and comparing their variability detected by SA-conf, we highlighted different sources of target flexibility such as induced by binding partner, by mutation and intrinsic flexibility. Our results support the interest to mine available structures associated with a target using to offer valuable insight into target flexibility and interaction mechanisms. The SA-conf executable script, with a set of pre-compiled binaries are available at

  11. Literature-based discovery of diabetes- and ROS-related targets

    Directory of Open Access Journals (Sweden)

    Pande Manjusha

    2010-10-01

    Full Text Available Abstract Background Reactive oxygen species (ROS are known mediators of cellular damage in multiple diseases including diabetic complications. Despite its importance, no comprehensive database is currently available for the genes associated with ROS. Methods We present ROS- and diabetes-related targets (genes/proteins collected from the biomedical literature through a text mining technology. A web-based literature mining tool, SciMiner, was applied to 1,154 biomedical papers indexed with diabetes and ROS by PubMed to identify relevant targets. Over-represented targets in the ROS-diabetes literature were obtained through comparisons against randomly selected literature. The expression levels of nine genes, selected from the top ranked ROS-diabetes set, were measured in the dorsal root ganglia (DRG of diabetic and non-diabetic DBA/2J mice in order to evaluate the biological relevance of literature-derived targets in the pathogenesis of diabetic neuropathy. Results SciMiner identified 1,026 ROS- and diabetes-related targets from the 1,154 biomedical papers (http://jdrf.neurology.med.umich.edu/ROSDiabetes/. Fifty-three targets were significantly over-represented in the ROS-diabetes literature compared to randomly selected literature. These over-represented targets included well-known members of the oxidative stress response including catalase, the NADPH oxidase family, and the superoxide dismutase family of proteins. Eight of the nine selected genes exhibited significant differential expression between diabetic and non-diabetic mice. For six genes, the direction of expression change in diabetes paralleled enhanced oxidative stress in the DRG. Conclusions Literature mining compiled ROS-diabetes related targets from the biomedical literature and led us to evaluate the biological relevance of selected targets in the pathogenesis of diabetic neuropathy.

  12. Nanobody-Based Delivery Systems for Diagnosis and Targeted Tumor Therapy

    Directory of Open Access Journals (Sweden)

    Yaozhong Hu

    2017-11-01

    Full Text Available The development of innovative targeted therapeutic approaches are expected to surpass the efficacy of current forms of treatments and cause less damage to healthy cells surrounding the tumor site. Since the first development of targeting agents from hybridoma’s, monoclonal antibodies (mAbs have been employed to inhibit tumor growth and proliferation directly or to deliver effector molecules to tumor cells. However, the full potential of such a delivery strategy is hampered by the size of mAbs, which will obstruct the targeted delivery system to access the tumor tissue. By serendipity, a new kind of functional homodimeric antibody format was discovered in camelidae, known as heavy-chain antibodies (HCAbs. The cloning of the variable domain of HCAbs produces an attractive minimal-sized alternative for mAbs, referred to as VHH or nanobodies (Nbs. Apart from their dimensions in the single digit nanometer range, the unique characteristics of Nbs combine a high stability and solubility, low immunogenicity and excellent affinity and specificity against all possible targets including tumor markers. This stimulated the development of tumor-targeted therapeutic strategies. Some autonomous Nbs have been shown to act as antagonistic drugs, but more importantly, the targeting capacity of Nbs has been exploited to create drug delivery systems. Obviously, Nb-based targeted cancer therapy is mainly focused toward extracellular tumor markers, since the membrane barrier prevents antibodies to reach the most promising intracellular tumor markers. Potential strategies, such as lentiviral vectors and bacterial type 3 secretion system, are proposed to deliver target-specific Nbs into tumor cells and to block tumor markers intracellularly. Simultaneously, Nbs have also been employed for in vivo molecular imaging to diagnose diseased tissues and to monitor the treatment effects. Here, we review the state of the art and focus on recent developments with Nbs as

  13. Mixture Statistical Distribution Based Multiple Component Model for Target Detection in High Resolution SAR Imagery

    Directory of Open Access Journals (Sweden)

    Chu He

    2017-11-01

    Full Text Available This paper proposes an innovative Mixture Statistical Distribution Based Multiple Component (MSDMC model for target detection in high spatial resolution Synthetic Aperture Radar (SAR images. Traditional detection algorithms usually ignore the spatial relationship among the target’s components. In the presented method, however, both the structural information and the statistical distribution are considered to better recognize the target. Firstly, the method based on compressed sensing reconstruction is used to recover the SAR image. Then, the multiple component model composed of a root filter and some corresponding part filters is applied to describe the structural information of the target. In the following step, mixture statistical distributions are utilised to discriminate the target from the background, and the Method of Logarithmic Cumulants (MoLC based Expectation Maximization (EM approach is adopted to estimate the parameters of the mixture statistical distribution model, which will be finally merged into the proposed MSDMC framework together with the multiple component model. In the experiment, the aeroplanes and the electrical power towers in TerraSAR-X SAR images are detected at three spatial resolutions. The results indicate that the presented MSDMC Model has potential for improving the detection performance compared with the state-of-the-art SAR target detection methods.

  14. Prediction of Drug-Target Interactions and Drug Repositioning via Network-Based Inference

    Science.gov (United States)

    Jiang, Jing; Lu, Weiqiang; Li, Weihua; Liu, Guixia; Zhou, Weixing; Huang, Jin; Tang, Yun

    2012-01-01

    Drug-target interaction (DTI) is the basis of drug discovery and design. It is time consuming and costly to determine DTI experimentally. Hence, it is necessary to develop computational methods for the prediction of potential DTI. Based on complex network theory, three supervised inference methods were developed here to predict DTI and used for drug repositioning, namely drug-based similarity inference (DBSI), target-based similarity inference (TBSI) and network-based inference (NBI). Among them, NBI performed best on four benchmark data sets. Then a drug-target network was created with NBI based on 12,483 FDA-approved and experimental drug-target binary links, and some new DTIs were further predicted. In vitro assays confirmed that five old drugs, namely montelukast, diclofenac, simvastatin, ketoconazole, and itraconazole, showed polypharmacological features on estrogen receptors or dipeptidyl peptidase-IV with half maximal inhibitory or effective concentration ranged from 0.2 to 10 µM. Moreover, simvastatin and ketoconazole showed potent antiproliferative activities on human MDA-MB-231 breast cancer cell line in MTT assays. The results indicated that these methods could be powerful tools in prediction of DTIs and drug repositioning. PMID:22589709

  15. A neutron production target for ESS based upon the Canned-rods concept

    International Nuclear Information System (INIS)

    Ghiglino, A.; Terrón, S.; Thomsen, K.; Wolters, J.; Magán, M.; Martínez, F.; Vicente, P.J. de; Vivanco, R.; Sordo, F.; Butzek, M.; Perlado, J.M.; Bermejo, F.J.

    2014-01-01

    The neutron production targets operating within the present day spallation neutron sources in the MW power range are either based on water-cooled solid state devices such as that implemented at the SINQ source at PSI or liquid metal loops such as those installed at SNS and MLSF. Here we describe a water-cooled rotating solid target as an option for the 5 MW ESS project as an alternative to the current design based upon a helium-cooled solid rotating target. Implementation of the proposed option would provide comparable neutronic performance to that of the gas-cooled concept and furthermore, it would involve a relatively straightforward adaptation of the current ESS baseline geometry

  16. A Method of SAR Target Recognition Based on Gabor Filter and Local Texture Feature Extraction

    Directory of Open Access Journals (Sweden)

    Wang Lu

    2015-12-01

    Full Text Available This paper presents a novel texture feature extraction method based on a Gabor filter and Three-Patch Local Binary Patterns (TPLBP for Synthetic Aperture Rader (SAR target recognition. First, SAR images are processed by a Gabor filter in different directions to enhance the significant features of the targets and their shadows. Then, the effective local texture features based on the Gabor filtered images are extracted by TPLBP. This not only overcomes the shortcoming of Local Binary Patterns (LBP, which cannot describe texture features for large scale neighborhoods, but also maintains the rotation invariant characteristic which alleviates the impact of the direction variations of SAR targets on recognition performance. Finally, we use an Extreme Learning Machine (ELM classifier and extract the texture features. The experimental results of MSTAR database demonstrate the effectiveness of the proposed method.

  17. Boronic acid-tethered amphiphilic hyaluronic acid derivative-based nanoassemblies for tumor targeting and penetration.

    Science.gov (United States)

    Jeong, Jae Young; Hong, Eun-Hye; Lee, Song Yi; Lee, Jae-Young; Song, Jae-Hyoung; Ko, Seung-Hak; Shim, Jae-Seong; Choe, Sunghwa; Kim, Dae-Duk; Ko, Hyun-Jeong; Cho, Hyun-Jong

    2017-04-15

    (3-Aminomethylphenyl)boronic acid (AMPB)-installed hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated for tumor-targeted delivery. The amine group of AMPB was conjugated to the carboxylic acid group of hyaluronic acid (HA) via amide bond formation, and synthesis was confirmed by spectroscopic methods. HACE-AMPB/MB NPs with a 239-nm mean diameter, narrow size distribution, negative zeta potential, and >90% drug encapsulation efficiency were fabricated. Exposed AMPB in the outer surface of HACE-AMPB NPs (in the aqueous environment) may react with sialic acid of cancer cells. The improved cellular accumulation efficiency, in vitro antitumor efficacy, and tumor penetration efficiency of HACE-AMPB/MB NPs, compared with HACE/MB NPs, in MDA-MB-231 cells (CD44 receptor-positive human breast adenocarcinoma cells) may be based on the CD44 receptor-mediated endocytosis and phenylboronic acid-sialic acid interaction. Enhanced in vivo tumor targetability, infiltration efficiency, and antitumor efficacies of HACE-AMPB NPs, compared with HACE NPs, were observed in a MDA-MB-231 tumor-xenografted mouse model. In addition to passive tumor targeting (based on an enhanced permeability and retention effect) and active tumor targeting (interaction between HA and CD44 receptor), the phenylboronic acid-sialic acid interaction can play important roles in augmented tumor targeting and penetration of HACE-AMPB NPs. STATEMENT OF SIGNIFICANCE: (3-Aminomethylphenyl)boronic acid (AMPB)-tethered hyaluronic acid-ceramide (HACE)-based nanoparticles (NPs), including manassantin B (MB), were fabricated and their tumor targeting and penetration efficiencies were assessed in MDA-MB-231 (CD44 receptor-positive human adenocarcinoma) tumor models. MB, which exhibited antitumor efficacies via the inhibition of angiogenesis and hypoxia inducible factor (HIF)-1, was entrapped in HACE-AMPB NPs in this study. Phenylboronic acid located in the outer surface

  18. Development and Implementation of New Control Law for Vision Based Target Tracking System Onboard Small Unmanned Aerial Vehicles

    National Research Council Canada - National Science Library

    Chong, Tay B

    2006-01-01

    ...) system onboard a small unmanned aerial vehicle (SUAV). The new control law allows for coordinated SUAV guidance and vision-based target tracking of stationary and moving targets in the presence of atmospheric disturbances and measurements noise...

  19. Dynamic RCS Simulation of a Missile Target Group Based on the High-frequency Asymptotic Method

    Directory of Open Access Journals (Sweden)

    Zhao Tao

    2014-04-01

    Full Text Available To simulate dynamic Radar Cross Section (RCS of missile target group, an efficient RCS prediction approach is proposed based on the high-frequency asymptotic theory. The minimal energy trajectory and coordinate transformation is used to get trajectories of the missile, decoys and roll booster, and establish the dynamic scene for the separate procedure of the target group, and the dynamic RCS including specular reflection, edge diffraction and multi-reflection from the target group are obtained by Physical Optics (PO, Equivalent Edge Currents (EEC and Shooting-and-Bouncing Ray (SBR methods. Compared with the dynamic RCS result with the common interpolation method, the proposed method is consistent with the common method when the targets in the scene are far away from each other and each target is not sheltered by others in the incident direction. When the target group is densely distributed and the shelter effect can not be neglected, the interpolation method is extremely difficult to realize, whereas the proposed method is successful.

  20. Spaceborne Regional Surveillance Ground Moving Target Indication Based on Squint-TOPSAR

    Directory of Open Access Journals (Sweden)

    Zeng Xiang-jie

    2015-08-01

    Full Text Available For military or civilian activities, it is important to monitor the direction of moving targets in a wide area. Traditional regional monitoring uses the airborne scanning mode (ScanSAR within the limits of the national airspace. The inherent characteristics of ScanSAR do not apply to spaceborne regional monitoring. In this paper, the spaceborne regional surveillance Ground Moving Target Indication (GMTI mode based on squint-TOPSAR is proposed. The proposed method uses the TOPSAR mode that improves the low SNR of spaceborne ScanSAR. The full-aperture imaging algorithm for squint-TOPSAR is used in data focusing. The Displaced Phase Center Antenna (DPCA and Constant False Alarm Rate (CFAR methods are used to accomplish the moving target indication. The relation between the interferometric phase and the speed of moving target is used to estimate the speed of the moving target and mark the target location in the SAR image. The differences between real and simulation data are analyzed. The simulation results demonstrate the effectiveness of the proposed method.

  1. Multi-UAV joint target recognizing based on binocular vision theory

    Directory of Open Access Journals (Sweden)

    Yuan Zhang

    2017-01-01

    Full Text Available Target recognizing of unmanned aerial vehicle (UAV based on image processing take the advantage of 2D information containing in the image for identifying the target. Compare to single UAV with electrical optical tracking system (EOTS, multi-UAV with EOTS is able to take a group of image focused on the suspected target from multiple view point. Benefit from matching each couple of image in this group, points set constituted by matched feature points implicates the depth of each point. Coordinate of target feature points could be computing from depth of feature points. This depth information makes up a cloud of points and reconstructed an exclusive 3D model to recognizing system. Considering the target recognizing do not require precise target model, the cloud of feature points was regrouped into n subsets and reconstructed to a semi-3D model. Casting these subsets in a Cartesian coordinate and applying these projections in convolutional neural networks (CNN respectively, the integrated output of networks is the improved result of recognizing.

  2. Comparison of "E-Rater"[R] Automated Essay Scoring Model Calibration Methods Based on Distributional Targets

    Science.gov (United States)

    Zhang, Mo; Williamson, David M.; Breyer, F. Jay; Trapani, Catherine

    2012-01-01

    This article describes two separate, related studies that provide insight into the effectiveness of "e-rater" score calibration methods based on different distributional targets. In the first study, we developed and evaluated a new type of "e-rater" scoring model that was cost-effective and applicable under conditions of absent human rating and…

  3. Homogeneous electrochemical aptamer-based ATP assay with signal amplification by exonuclease III assisted target recycling.

    Science.gov (United States)

    Liu, Shufeng; Wang, Ying; Zhang, Chengxin; Lin, Ying; Li, Feng

    2013-03-21

    A novel and homogeneous electrochemical aptamer-based adenosine triphosphate (ATP) assay was demonstrated with signal amplification by exonuclease III-assisted target recycling. A superior detection limit of 1 nM toward ATP with an excellent selectivity could be achieved.

  4. Targeting Fear of Spiders with Control-, Acceptance-, and Information-Based Approaches

    Science.gov (United States)

    Wagener, Alexandra L.; Zettle, Robert D.

    2011-01-01

    The relative impact of control-, acceptance-, and information-based approaches in targeting a midlevel fear of spiders among college students was evaluated. Participants listened to a brief protocol presenting one of the three approaches before completing the Perceived-Threat Behavioral Approach Test (PT-BAT; Cochrane, Barnes-Holmes, &…

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  6. Risk-Based Treatment Targets for Onsite Non-Potable Water Reuse

    Science.gov (United States)

    This presentation presents risk-based enteric pathogen log reduction targets for non-potable and potable uses of a variety of alternative source waters (i.e., municipal wastewater, locally-collected greywater, rainwater, and stormwater). A probabilistic, forward Quantitative Micr...

  7. Regional GHG reduction targets based on effort sharing: a comparison of studies

    NARCIS (Netherlands)

    Höhne, N.; Elzen, den M.G.J.; Escalante, D.

    2014-01-01

    Over 40 studies that analyse future GHG emissions allowances or reduction targets for different regions based on a wide range of effort-sharing approaches and long-term concentration stabilization levels are compared. This updates previous work undertaken for the Fourth Assessment Report of the

  8. Yeast-based assay identifies novel Shh/Gli target genes in vertebrate development

    Directory of Open Access Journals (Sweden)

    Milla Luis A

    2012-01-01

    Full Text Available Abstract Background The increasing number of developmental events and molecular mechanisms associated with the Hedgehog (Hh pathway from Drosophila to vertebrates, suggest that gene regulation is crucial for diverse cellular responses, including target genes not yet described. Although several high-throughput, genome-wide approaches have yielded information at the genomic, transcriptional and proteomic levels, the specificity of Gli binding sites related to direct target gene activation still remain elusive. This study aims to identify novel putative targets of Gli transcription factors through a protein-DNA binding assay using yeast, and validating a subset of targets both in-vitro and in-vivo. Testing in different Hh/Gli gain- and loss-of-function scenarios we here identified known (e.g., ptc1 and novel Hh-regulated genes in zebrafish embryos. Results The combined yeast-based screening and MEME/MAST analysis were able to predict Gli transcription factor binding sites, and position mapping of these sequences upstream or in the first intron of promoters served to identify new putative target genes of Gli regulation. These candidates were validated by qPCR in combination with either the pharmacological Hh/Gli antagonist cyc or the agonist pur in Hh-responsive C3H10T1/2 cells. We also used small-hairpin RNAs against Gli proteins to evaluate targets and confirm specific Gli regulation their expression. Taking advantage of mutants that have been identified affecting different components of the Hh/Gli signaling system in the zebrafish model, we further analyzed specific novel candidates. Studying Hh function with pharmacological inhibition or activation complemented these genetic loss-of-function approaches. We provide evidence that in zebrafish embryos, Hh signaling regulates sfrp2, neo1, and c-myc expression in-vivo. Conclusion A recently described yeast-based screening allowed us to identify new Hh/Gli target genes, functionally important in

  9. High neutronic efficiency, low current targets for accelerator-based BNCT applications

    International Nuclear Information System (INIS)

    Powell, J.R.; Ludewig, H.; Todosow, M.

    1998-01-01

    The neutronic efficiency of target/filters for accelerator-based BNCT applications is measured by the proton current required to achieve a desirable neutron current at the treatment port (10 9 n/cm 2 /s). In this paper the authors describe two possible targeyt/filter concepts wihch minimize the required current. Both concepts are based on the Li-7 (p,n)Be-7 reaction. Targets that operate near the threshold energy generate neutrons that are close tothe desired energy for BNCT treatment. Thus, the filter can be extremely thin (∼ 5 cm iron). However, this approach has an extremely low neutron yield (n/p ∼ 1.0(-6)), thus requiring a high proton current. The proposed solutino is to design a target consisting of multiple extremely thin targets (proton energy loss per target ∼ 10 keV), and re-accelerate the protons between each target. Targets operating at ihgher proton energies (∼ 2.5 MeV) have a much higher yield (n/p ∼ 1.0(-4)). However, at these energies the maximum neutron energy is approximately 800 keV, and thus a neutron filter is required to degrade the average neutron energy to the range of interest for BNCT (10--20 keV). A neutron filter consisting of fluorine compounds and iron has been investigated for this case. Typically a proton current of approximately 5 mA is required to generate the desired neutron current at the treatment port. The efficiency of these filter designs can be further increased by incorporating neutron reflectors that are co-axial with the neutron source. These reflectors are made of materials which have high scattering cross sections in the range 0.1--1.0 MeV

  10. Multi-target trapping in constrained environments using gene regulatory network-based pattern formation

    Directory of Open Access Journals (Sweden)

    Xingguang Peng

    2016-10-01

    Full Text Available Inspired by the morphogenesis of biological organisms, gene regulatory network-based methods have been used in complex pattern formation of swarm robotic systems. In this article, obstacle information was embedded into the gene regulatory network model to make the robots trap targets with an expected pattern while avoiding obstacles in a distributed manner. Based on the modified gene regulatory network model, an implicit function method was adopted to represent the expected pattern which is easily adjusted by adding extra feature points. Considering environmental constraints (e.g. tunnels or gaps in which robots must adjust their pattern to conduct trapping task, a pattern adaptation strategy was proposed for the pattern modeler to adaptively adjust the expected pattern. Also to trap multiple targets, a splitting pattern adaptation strategy was proposed for diffusively moving targets so that the robots can trap each target separately with split sub-patterns. The proposed model and strategies were verified through a set of simulation with complex environmental constraints and non-consensus movements of targets.

  11. Random projection-based dimensionality reduction method for hyperspectral target detection

    Science.gov (United States)

    Feng, Weiyi; Chen, Qian; He, Weiji; Arce, Gonzalo R.; Gu, Guohua; Zhuang, Jiayan

    2015-09-01

    Dimensionality reduction is a frequent preprocessing step in hyperspectral image analysis. High-dimensional data will cause the issue of the "curse of dimensionality" in the applications of hyperspectral imagery. In this paper, a dimensionality reduction method of hyperspectral images based on random projection (RP) for target detection was investigated. In the application areas of hyperspectral imagery, e.g. target detection, the high dimensionality of the hyperspectral data would lead to burdensome computations. Random projection is attractive in this area because it is data independent and computationally more efficient than other widely-used hyperspectral dimensionality-reduction methods, such as Principal Component Analysis (PCA) or the maximum-noise-fraction (MNF) transform. In RP, the original highdimensional data is projected onto a low dimensional subspace using a random matrix, which is very simple. Theoretical and experimental results indicated that random projections preserved the structure of the original high-dimensional data quite well without introducing significant distortion. In the experiments, Constrained Energy Minimization (CEM) was adopted as the target detector and a RP-based CEM method for hyperspectral target detection was implemented to reveal that random projections might be a good alternative as a dimensionality reduction tool of hyperspectral images to yield improved target detection with higher detection accuracy and lower computation time than other methods.

  12. Synthetic Aperture Radar Target Recognition with Feature Fusion Based on a Stacked Autoencoder

    Directory of Open Access Journals (Sweden)

    Miao Kang

    2017-01-01

    Full Text Available Feature extraction is a crucial step for any automatic target recognition process, especially in the interpretation of synthetic aperture radar (SAR imagery. In order to obtain distinctive features, this paper proposes a feature fusion algorithm for SAR target recognition based on a stacked autoencoder (SAE. The detailed procedure presented in this paper can be summarized as follows: firstly, 23 baseline features and Three-Patch Local Binary Pattern (TPLBP features are extracted. These features can describe the global and local aspects of the image with less redundancy and more complementarity, providing richer information for feature fusion. Secondly, an effective feature fusion network is designed. Baseline and TPLBP features are cascaded and fed into a SAE. Then, with an unsupervised learning algorithm, the SAE is pre-trained by greedy layer-wise training method. Capable of feature expression, SAE makes the fused features more distinguishable. Finally, the model is fine-tuned by a softmax classifier and applied to the classification of targets. 10-class SAR targets based on Moving and Stationary Target Acquisition and Recognition (MSTAR dataset got a classification accuracy up to 95.43%, which verifies the effectiveness of the presented algorithm.

  13. Machine Learning Consensus Scoring Improves Performance Across Targets in Structure-Based Virtual Screening.

    Science.gov (United States)

    Ericksen, Spencer S; Wu, Haozhen; Zhang, Huikun; Michael, Lauren A; Newton, Michael A; Hoffmann, F Michael; Wildman, Scott A

    2017-07-24

    In structure-based virtual screening, compound ranking through a consensus of scores from a variety of docking programs or scoring functions, rather than ranking by scores from a single program, provides better predictive performance and reduces target performance variability. Here we compare traditional consensus scoring methods with a novel, unsupervised gradient boosting approach. We also observed increased score variation among active ligands and developed a statistical mixture model consensus score based on combining score means and variances. To evaluate performance, we used the common performance metrics ROCAUC and EF1 on 21 benchmark targets from DUD-E. Traditional consensus methods, such as taking the mean of quantile normalized docking scores, outperformed individual docking methods and are more robust to target variation. The mixture model and gradient boosting provided further improvements over the traditional consensus methods. These methods are readily applicable to new targets in academic research and overcome the potentially poor performance of using a single docking method on a new target.

  14. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    OpenAIRE

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.; Bruns, Christiane J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associa...

  15. Magnetic nanoparticle-based approaches to locally target therapy and enhance tissue regeneration in vivo

    Science.gov (United States)

    Sensenig, Richard; Sapir, Yulia; MacDonald, Cristin; Cohen, Smadar; Polyak, Boris

    2013-01-01

    Magnetic-based systems utilizing superparamagnetic nanoparticles and a magnetic field gradient to exert a force on these particles have been used in a wide range of biomedical applications. This review is focused on drug targeting applications that require penetration of a cellular barrier as well as strategies to improve the efficacy of targeting in these biomedical applications. Another focus of this review is regenerative applications utilizing tissue engineered scaffolds prepared with the aid of magnetic particles, the use of remote actuation for release of bioactive molecules and magneto–mechanical cell stimulation, cell seeding and cell patterning. PMID:22994959

  16. Target Detection in SAR Images Based on a Level Set Approach

    Energy Technology Data Exchange (ETDEWEB)

    Marques, Regis C.P.; Medeiros, Fatima N.S.; Ushizima, Daniela M.

    2008-09-01

    This paper introduces a new framework for point target detection in synthetic aperture radar (SAR) images. We focus on the task of locating reflective small regions using alevel set based algorithm. Unlike most of the approaches in image segmentation, we address an algorithm which incorporates speckle statistics instead of empirical parameters and also discards speckle filtering. The curve evolves according to speckle statistics, initially propagating with a maximum upward velocity in homogeneous areas. Our approach is validated by a series of tests on synthetic and real SAR images and compared with three other segmentation algorithms, demonstrating that it configures a novel and efficient method for target detection purpose.

  17. The performance analysis of sonar target tracking based on pressure hydrophone arrays

    Science.gov (United States)

    Chen, Zhe; Liu, Qijun; Li, Zhizhong

    2017-06-01

    For the linear array sonar that consists of pressure hydrophones, it is difficult to solve the problem of port/starboard ambiguity. To estimate the target’s real azimuth accurately, the conventional beam forming methods of different arrays which include linear array, arc array, cross array and Y-shaped array were analysed. Based on the port/starboard discrimination ability and beam width, the sonar target tracking performance of different arrays was compared. It is shown that all arrays except the linear array could discriminate the real target, and the arc array’s effect is the best.

  18. Agent-based multi-platform control, collaboration, and target hand-off

    Science.gov (United States)

    Coleman, Norm; Tirabassi, Ben; MacKenzie, Doug

    2007-04-01

    Deploying a world wide force that is strategically responsive and dominant at every point on the spectrum of conflict involves the cooperative system development and use of advanced technologies that yield revolutionary capabilities to support the war-fighters needs. This presentation describes an agent based control architecture and prototype implementation developed by ARDEC that enables command and control of multiple unmanned platforms and associated mission packages for collaborative target hand-off/engagement. Current prototypes provide the ability to remotely locate, track and predict the movement of enemy targets on the battlefield using a variety of sensor systems hosted on multiple, non-homogeneous SUAVs and UGVs.

  19. Multirapid Serial Visual Presentation Framework for EEG-Based Target Detection

    Directory of Open Access Journals (Sweden)

    Zhimin Lin

    2017-01-01

    Full Text Available Target image detection based on a rapid serial visual presentation (RSVP paradigm is a typical brain-computer interface system with various applications, such as image retrieval. In an RSVP paradigm, a P300 component is detected to determine target images. This strategy requires high-precision single-trial P300 detection methods. However, the performance of single-trial detection methods is relatively lower than that of multitrial P300 detection methods. Image retrieval based on multitrial P300 is a new research direction. In this paper, we propose a triple-RSVP paradigm with three images being presented simultaneously and a target image appearing three times. Thus, multitrial P300 classification methods can be used to improve detection accuracy. In this study, these mechanisms were extended and validated, and the characteristics of the multi-RSVP framework were further explored. Two different P300 detection algorithms were also utilized in multi-RSVP to demonstrate that the scheme is universally applicable. Results revealed that the detection accuracy of the multi-RSVP paradigm was higher than that of the standard RSVP paradigm. The results validate the effectiveness of the proposed method, and this method can provide a whole new idea in the field of EEG-based target detection.

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

    Science.gov (United States)

    Caldwell, Gary W

    2015-01-01

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

  1. Single base mismatches in the mRNA target site allow specific seed region-mediated off-target binding of siRNA targeting human coagulation factor 7.

    Science.gov (United States)

    Ravon, Morgane; Berrera, Marco; Ebeling, Martin; Certa, Ulrich

    2012-01-01

    We have analyzed the off-target activity of two siRNAs (F7-1, F7-2) that knock-down human blood coagulation factor 7 mRNA. F7-1 modulates a significant number of non-target transcripts while F7-2 shows high selectivity for the target transcript under various experimental conditions. The 3'-UTRs of all F7-1 off-target genes show statistically significant enrichment of the reverse complement of the F7-1 siRNA seed region located in the guide strand. Seed region enrichment was confirmed in off-target transcripts modulated by siRNA targeting the glucocorticoid receptor. To investigate how these sites contribute to off-target recognition of F7-1, we employed CXCL5 transcript as model system because it contains five F7-1 seed sequence motifs with single base mismatches. We show by transient transfection of reporter gene constructs into HEK293 cells that three out of five sites located in the 3'-UTR region are required for F7-1 off-target activity. For further mechanistic dissection, the sequences of these sites were synthesized and inserted either individually or joined in dimeric or trimeric constructs. Only the fusion constructs were silenced by F7-1 while the individual sites had no off-target activity. Based on F7-1 as a model, a single mismatch between the siRNA seed region and mRNA target sites is tolerated for target recognition and the CXCL5 data suggest a requirement for binding to multiple target sites in off-target transcripts.

  2. Setting up GHG-based energy efficiency targets in buildings: The Ecolabel

    International Nuclear Information System (INIS)

    José Vinagre Díaz, Juan; Richard Wilby, Mark; Belén Rodríguez González, Ana

    2013-01-01

    The European Union has recently updated the regulations for energy performance of buildings and on the certification of energy-related products. The world is in the process of constructing policy frameworks to underwrite carbon emission reduction targets, best exemplified by the Kyoto Protocol. This requires complex technical and economical concepts to be presented in an understandable, transparent, and justifiable format. A building's energy efficiency was traditionally determined based on its annual consumption relative to some average performance level. Emissions are calculated as a derivative of consumptions and their aggregated values allow verification of the level of fulfillment of the objectives. Here we take a different approach: considering that the greenhouse gas emissions (GHG) objectives must be achieved; hence, we fix the efficiency standard based on emissions objectives, and then derive the corresponding reference values of consumption. Accordingly, we propose a certification scheme for energy efficiency in buildings based on targets of GHG emissions levels. This proposed framework includes both a label, namely the Ecolabel, and a fiche showing a set of indices and complementary information. The Ecolabel is designed to provide a flexible, evolvable, simple to use at the point of application, and transparent framework. - Highlights: • In this paper we consider the interaction between greenhouse gas emission reduction targets and building energy efficiency. • Specifically we propose an ‘‘Ecolabel” for buildings that is a GHG emissions liability index, which forms a labeling process. • The label follows the Kyoto Protocol philosophy and translates national GHG targets to targets for each and every building. • The approach provides both a new form of efficiency rating on which emissions reduction policy can be based

  3. Generating Alignments Using Target Foresight in Attention-Based Neural Machine Translation

    Directory of Open Access Journals (Sweden)

    Peter Jan-Thorsten

    2017-06-01

    Full Text Available Neural machine translation (NMT has shown large improvements in recent years. The currently most successful approach in this area relies on the attention mechanism, which is often interpreted as an alignment, even though it is computed without explicit knowledge of the target word. This limitation is the most likely reason that the quality of attention-based alignments is inferior to the quality of traditional alignment methods. Guided alignment training has shown that alignments are still capable of improving translation quality. In this work, we propose an extension of the attention-based NMT model that introduces target information into the attention mechanism to produce high-quality alignments. In comparison to the conventional attention-based alignments, our model halves the Aer with an absolute improvement of 19.1% Aer. Compared to GIZA++ it shows an absolute improvement of 2.0% Aer.

  4. lncRNATargets: A platform for lncRNA target prediction based on nucleic acid thermodynamics.

    Science.gov (United States)

    Hu, Ruifeng; Sun, Xiaobo

    2016-08-01

    Many studies have supported that long noncoding RNAs (lncRNAs) perform various functions in various critical biological processes. Advanced experimental and computational technologies allow access to more information on lncRNAs. Determining the functions and action mechanisms of these RNAs on a large scale is urgently needed. We provided lncRNATargets, which is a web-based platform for lncRNA target prediction based on nucleic acid thermodynamics. The nearest-neighbor (NN) model was used to calculate binging-free energy. The main principle of NN model for nucleic acid assumes that identity and orientation of neighbor base pairs determine stability of a given base pair. lncRNATargets features the following options: setting of a specific temperature that allow use not only for human but also for other animals or plants; processing all lncRNAs in high throughput without RNA size limitation that is superior to any other existing tool; and web-based, user-friendly interface, and colored result displays that allow easy access for nonskilled computer operators and provide better understanding of results. This technique could provide accurate calculation on the binding-free energy of lncRNA-target dimers to predict if these structures are well targeted together. lncRNATargets provides high accuracy calculations, and this user-friendly program is available for free at http://www.herbbol.org:8001/lrt/ .

  5. Predicting targeted drug combinations based on Pareto optimal patterns of coexpression network connectivity.

    Science.gov (United States)

    Penrod, Nadia M; Greene, Casey S; Moore, Jason H

    2014-01-01

    Molecularly targeted drugs promise a safer and more effective treatment modality than conventional chemotherapy for cancer patients. However, tumors are dynamic systems that readily adapt to these agents activating alternative survival pathways as they evolve resistant phenotypes. Combination therapies can overcome resistance but finding the optimal combinations efficiently presents a formidable challenge. Here we introduce a new paradigm for the design of combination therapy treatment strategies that exploits the tumor adaptive process to identify context-dependent essential genes as druggable targets. We have developed a framework to mine high-throughput transcriptomic data, based on differential coexpression and Pareto optimization, to investigate drug-induced tumor adaptation. We use this approach to identify tumor-essential genes as druggable candidates. We apply our method to a set of ER(+) breast tumor samples, collected before (n = 58) and after (n = 60) neoadjuvant treatment with the aromatase inhibitor letrozole, to prioritize genes as targets for combination therapy with letrozole treatment. We validate letrozole-induced tumor adaptation through coexpression and pathway analyses in an independent data set (n = 18). We find pervasive differential coexpression between the untreated and letrozole-treated tumor samples as evidence of letrozole-induced tumor adaptation. Based on patterns of coexpression, we identify ten genes as potential candidates for combination therapy with letrozole including EPCAM, a letrozole-induced essential gene and a target to which drugs have already been developed as cancer therapeutics. Through replication, we validate six letrozole-induced coexpression relationships and confirm the epithelial-to-mesenchymal transition as a process that is upregulated in the residual tumor samples following letrozole treatment. To derive the greatest benefit from molecularly targeted drugs it is critical to design combination

  6. Type I-E CRISPR-Cas Systems Discriminate Target from Non-Target DNA through Base Pairing-Independent PAM Recognition

    Science.gov (United States)

    Datsenko, Kirill A.; Jackson, Ryan N.; Wiedenheft, Blake; Severinov, Konstantin; Brouns, Stan J. J.

    2013-01-01

    Discriminating self and non-self is a universal requirement of immune systems. Adaptive immune systems in prokaryotes are centered around repetitive loci called CRISPRs (clustered regularly interspaced short palindromic repeat), into which invader DNA fragments are incorporated. CRISPR transcripts are processed into small RNAs that guide CRISPR-associated (Cas) proteins to invading nucleic acids by complementary base pairing. However, to avoid autoimmunity it is essential that these RNA-guides exclusively target invading DNA and not complementary DNA sequences (i.e., self-sequences) located in the host's own CRISPR locus. Previous work on the Type III-A CRISPR system from Staphylococcus epidermidis has demonstrated that a portion of the CRISPR RNA-guide sequence is involved in self versus non-self discrimination. This self-avoidance mechanism relies on sensing base pairing between the RNA-guide and sequences flanking the target DNA. To determine if the RNA-guide participates in self versus non-self discrimination in the Type I-E system from Escherichia coli we altered base pairing potential between the RNA-guide and the flanks of DNA targets. Here we demonstrate that Type I-E systems discriminate self from non-self through a base pairing-independent mechanism that strictly relies on the recognition of four unchangeable PAM sequences. In addition, this work reveals that the first base pair between the guide RNA and the PAM nucleotide immediately flanking the target sequence can be disrupted without affecting the interference phenotype. Remarkably, this indicates that base pairing at this position is not involved in foreign DNA recognition. Results in this paper reveal that the Type I-E mechanism of avoiding self sequences and preventing autoimmunity is fundamentally different from that employed by Type III-A systems. We propose the exclusive targeting of PAM-flanked sequences to be termed a target versus non-target discrimination mechanism. PMID:24039596

  7. A colon targeted drug delivery system based on alginate modificated graphene oxide for colorectal liver metastasis.

    Science.gov (United States)

    Zhang, Bin; Yan, Yayuan; Shen, Qiujuan; Ma, Dong; Huang, Langhuan; Cai, Xiang; Tan, Shaozao

    2017-10-01

    A major problem associated with colon cancer is liver metastasis. A colon-targeted drug delivery system is one way to address this problem after the resection of colorectal cancer. However, traditional drug delivery systems face many challenges, such as an inability to control the release rate, inaccurate targeting, susceptibility to the microenvironment and poor stability. Here, we report the development of a graphene oxide (GO)-based, sodium alginate (ALG) functionalized colon-targeting drug delivery system, that is loaded with 5-fluorouracil (5-FU) as the anti-cancer drug (denoted as GO-ALG/5-FU). Our results demonstrate that the as-prepared drug delivery system possesses a much lower toxicity and better colon-targeting controlled-release behaviours. We show that GO-ALG/5-FU significantly inhibited tumour growth and liver metastasis and prolonged the survival time of mice. We anticipate that our assay will help improve basic research of colon-targeted drug delivery systems and provide a new way to treat colon cancer liver metastasis. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Effect of advanced nanowire-based targets in nanosecond laser-matter interaction (invited).

    Science.gov (United States)

    Lanzalone, G; Altana, C; Mascali, D; Muoio, A; Malferrari, L; Odorici, F; Malandrino, G; Tudisco, S

    2016-02-01

    An experimental campaign aiming to investigate the effects of innovative nanostructured targets based on Ag nanowires on laser energy absorption in the ns time domain has been carried out at the Laser Energy for Nuclear Science laboratory of INFN-LNS in Catania. The tested targets were realized at INFN-Bologna by anodizing aluminium sheets in order to obtain layers of porous Al2O3 of different thicknesses, on which nanowires of various metals are grown by electro-deposition with different heights. Targets were then irradiated by using a Nd:YAG laser at different pumping energies. Advanced diagnostic tools were used for characterizing the plasma plume and ion production. As compared with targets of pure Al, a huge enhancement (of almost two order of magnitude) of the X-ray flux emitted by the plasma has been observed when using the nanostructured targets, with a corresponding decrease of the "optical range" signal, pointing out that the energetic content of the laser produced plasma was remarkably increased. This analysis was furthermore confirmed from time-of-flight spectra.

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

    Directory of Open Access Journals (Sweden)

    Jia Xu

    2016-10-01

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

  10. Pricise Target Geolocation Based on Integeration of Thermal Video Imagery and Rtk GPS in Uavs

    Science.gov (United States)

    Hosseinpoor, H. R.; Samadzadegan, F.; Dadras Javan, F.

    2015-12-01

    There are an increasingly large number of uses for Unmanned Aerial Vehicles (UAVs) from surveillance, mapping and target geolocation. However, most of commercial UAVs are equipped with low-cost navigation sensors such as C/A code GPS and a low-cost IMU on board, allowing a positioning accuracy of 5 to 10 meters. This low accuracy which implicates that it cannot be used in applications that require high precision data on cm-level. This paper presents a precise process for geolocation of ground targets based on thermal video imagery acquired by small UAV equipped with RTK GPS. The geolocation data is filtered using a linear Kalman filter, which provides a smoothed estimate of target location and target velocity. The accurate geo-locating of targets during image acquisition is conducted via traditional photogrammetric bundle adjustment equations using accurate exterior parameters achieved by on board IMU and RTK GPS sensors and Kalman filtering and interior orientation parameters of thermal camera from pre-flight laboratory calibration process.

  11. PRICISE TARGET GEOLOCATION BASED ON INTEGERATION OF THERMAL VIDEO IMAGERY AND RTK GPS IN UAVS

    Directory of Open Access Journals (Sweden)

    H. R. Hosseinpoor

    2015-12-01

    Full Text Available There are an increasingly large number of uses for Unmanned Aerial Vehicles (UAVs from surveillance, mapping and target geolocation. However, most of commercial UAVs are equipped with low-cost navigation sensors such as C/A code GPS and a low-cost IMU on board, allowing a positioning accuracy of 5 to 10 meters. This low accuracy which implicates that it cannot be used in applications that require high precision data on cm-level. This paper presents a precise process for geolocation of ground targets based on thermal video imagery acquired by small UAV equipped with RTK GPS. The geolocation data is filtered using a linear Kalman filter, which provides a smoothed estimate of target location and target velocity. The accurate geo-locating of targets during image acquisition is conducted via traditional photogrammetric bundle adjustment equations using accurate exterior parameters achieved by on board IMU and RTK GPS sensors and Kalman filtering and interior orientation parameters of thermal camera from pre-flight laboratory calibration process.

  12. Node Topology Effect on Target Tracking Based on UWSNs Using Quantized Measurements.

    Science.gov (United States)

    Zhang, Qiang; Liu, Meiqin; Zhang, Senlin

    2015-10-01

    On one hand, due to the energy and bandwidth constraint of underwater wireless sensor networks (UWSNs), local data quantization/compression is not only a necessity, but also an integral part of the design of UWSNs; on the other hand, since underwater nodes provide measurements for target tracking based on UWSNs, node topology, which is made up of the underwater nodes, may affect the performance of target tracking. This paper studies the effect of node topology on the target tracking in UWSNs using quantized measurements. Firstly, by using the knowledge of geometry, the effects of four typical topologies on target tracking using quantized measurements are analyzed qualitatively. The four typical topologies include two nodes are close to each other, three nodes are close to each other, three nodes are co-linear, and three nodes form a regular triangle. Secondly, under the condition of quantized measurements, the relationship between the posterior Cramer-Rao lower bound (PCRLB) and node's position is derived to evaluate the arbitrary topology. Thirdly, our target tracking scheme consisting of the optimal topology selection scheme by minimizing PCRLB, the optimal fusion center selection scheme by minimizing energy consumption, and the multisensor particle filter with quantized measurements is designed. Last, simulation results show the effectiveness of the proposed scheme.

  13. Design and implement of infrared small target real-time detection system based on pipeline technology

    Science.gov (United States)

    Sun, Lihui; Wang, Yongzhong; He, Yongqiang

    2007-01-01

    The detection for motive small target in infrared image sequence has become a hot topic nowadays. Background suppress algorithm based on minim gradient median filter and temporal recursion target detection algorithm are introduced. On the basis of contents previously mentioned, a four stages pipeline structure infrared small target detection process system, which aims at characters of algorithm complexity, large amounts of data to process, high frame frequency and exigent real-time character in this kind of application, is designed and implemented. The logical structure of the system was introduced and the function and signals flows are programmed. The system is composed of two FPGA chips and two DSP chips of TI. According to the function of each part, the system is divided into image preprocess stage, target detection stage, track relation stage and image output stage. The experiment of running algorithms on the system presented in this paper proved that the system could meet acquisition and process of 50Hz 240x320 digital image and the system could real time detect small target with a signal-noise ratio more than 3 reliably. The system achieves the characters of large amount of memory, high real-time processing, excellent extension and favorable interactive interface.

  14. Target Diagnostic Instrument-Based Controls Framework for the National Ignition Facility

    International Nuclear Information System (INIS)

    Shelton, R; O'Brien, D; Nelson, J; Kamperschroer, J

    2007-01-01

    NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including various neutron and activation diagnostics. NIF's diagnostics are being developed at LLNL and with collaborators at other sites. To accommodate the growing number of target diagnostics, an Instrument-Based Controls hardware-software framework has been developed to facilitate development and ease integration into the NIF Integrated Computer Control System (ICCS). Individual WindowsXP PC controllers for each digitizer, power supply and camera (i.e., instruments) execute controls software unique to each instrument model. Each hardware-software controller manages a single instrument, in contrast to the complexity of combining all the controls software needed for a diagnostic into a single controller. Because of this simplification, controllers can be more easily tested on the actual hardware, evaluating all normal and off-normal conditions. Each target diagnostic is then supported by a number of instruments, each with its own hardware-software instrument-based controller. Advantages of the instrument-based control architecture and framework include reusability, testability, and improved reliability of the deployed

  15. Target Diagnostic Instrument-Based Controls Framework for the National Ignition Facility

    Energy Technology Data Exchange (ETDEWEB)

    Shelton, R; O' Brien, D; Nelson, J; Kamperschroer, J

    2007-05-07

    NIF target diagnostics are being developed to observe and measure the extreme physics of targets irradiated by the 192-beam laser. The response time of target materials can be on the order of 100ps--the time it takes light to travel 3 cm--temperatures more than 100 times hotter than the surface of the sun, and pressures that exceed 109 atmospheres. Optical and x-ray diagnostics were developed and fielded to observe and record the results of the first 4-beam experiments at NIF. Hard and soft x-ray spectra were measured, and time-integrated and gated x-ray images of hydrodynamics experiments were recorded. Optical diagnostics recorded backscatter from the target, and VISAR laser velocimetry measurements were taken of laser-shocked target surfaces. Additional diagnostics are being developed and commissioned to observe and diagnose ignition implosions, including various neutron and activation diagnostics. NIF's diagnostics are being developed at LLNL and with collaborators at other sites. To accommodate the growing number of target diagnostics, an Instrument-Based Controls hardware-software framework has been developed to facilitate development and ease integration into the NIF Integrated Computer Control System (ICCS). Individual WindowsXP PC controllers for each digitizer, power supply and camera (i.e., instruments) execute controls software unique to each instrument model. Each hardware-software controller manages a single instrument, in contrast to the complexity of combining all the controls software needed for a diagnostic into a single controller. Because of this simplification, controllers can be more easily tested on the actual hardware, evaluating all normal and off-normal conditions. Each target diagnostic is then supported by a number of instruments, each with its own hardware-software instrument-based controller. Advantages of the instrument-based control architecture and framework include reusability, testability, and improved reliability of the

  16. Mesenchymal Stem Cell-Based Tumor-Targeted Gene Therapy in Gastrointestinal Cancer

    Science.gov (United States)

    Bao, Qi; Zhao, Yue; Niess, Hanno; Conrad, Claudius; Schwarz, Bettina; Jauch, Karl-Walter; Huss, Ralf; Nelson, Peter J.

    2012-01-01

    Mesenchymal stem (or stromal) cells (MSCs) are nonhematopoietic progenitor cells that can be obtained from bone marrow aspirates or adipose tissue, expanded and genetically modified in vitro, and then used for cancer therapeutic strategies in vivo. Here, we review available data regarding the application of MSC-based tumor-targeted therapy in gastrointestinal cancer, provide an overview of the general history of MSC-based gene therapy in cancer research, and discuss potential problems associated with the utility of MSC-based therapy such as biosafety, immunoprivilege, transfection methods, and distribution in the host. PMID:22530882

  17. Understanding the fate of chlorogenic acids in coffee roasting using mass spectrometry based targeted and non-targeted analytical strategies.

    Science.gov (United States)

    Jaiswal, Rakesh; Matei, Marius F; Golon, Agnieszka; Witt, Matthias; Kuhnert, Nikolai

    2012-09-01

    Coffee is one of mankind's most popular beverages obtained from green coffee beans by roasting. Much effort has been expended towards the chemical characterisation of the components of the roasted coffee bean, frequently termed melanoidines, which are dominated byproducts formed from its most relevant secondary metabolites - chlorogenic acids. However, impeded by a lack of suitable authentic reference standards and analytical techniques sufficiently powerful for providing insight into an extraordinarily complex enigmatic material, unsurprisingly little structural and mechanistic information about the products of coffee roasting is available. Here we report on the characterisation of low molecular weight melanoidine fractions of roasted coffee using a conceptually novel combination of targeted and non-targeted mass spectrometrical techniques. We provide an unprecedented account of the chemical composition of roasted coffee beans. Using a targeted analytical approach we show for the first time, by comparison to authentic reference standards obtained by chemical synthesis, that chlorogenic acids follow four distinct reaction pathways including epimerization, acyl migration, lactonisation and dehydration. The analytical strategy employed in a non-targeted approach uses high resolution mass spectrometry to identify the most abundant molecular formulas present in roasted coffee samples and model roasts followed by van Krevelen and homologous series analysis. We identified the molecular formulas formed from reactions of chlorogenic acids, carbohydrates and proteins, both between classes of compounds and within same classes of compounds. Furthermore, we identified two new classes of compounds formed from chlorogenic acids during roasting, chlorogenic acid acetates and O-phenolic quinoyl and shikimoyl esters of chlorogenic acids.

  18. Tumor-targeting delivery of herb-based drugs with cell-penetrating/tumor-targeting peptide-modified nanocarriers.

    Science.gov (United States)

    Kebebe, Dereje; Liu, Yuanyuan; Wu, Yumei; Vilakhamxay, Maikhone; Liu, Zhidong; Li, Jiawei

    2018-01-01

    Cancer has become one of the leading causes of mortality globally. The major challenges of conventional cancer therapy are the failure of most chemotherapeutic agents to accumulate selectively in tumor cells and their severe systemic side effects. In the past three decades, a number of drug delivery approaches have been discovered to overwhelm the obstacles. Among these, nanocarriers have gained much attention for their excellent and efficient drug delivery systems to improve specific tissue/organ/cell targeting. In order to enhance targeting efficiency further and reduce limitations of nanocarriers, nanoparticle surfaces are functionalized with different ligands. Several kinds of ligand-modified nanomedicines have been reported. Cell-penetrating peptides (CPPs) are promising ligands, attracting the attention of researchers due to their efficiency to transport bioactive molecules intracellularly. However, their lack of specificity and in vivo degradation led to the development of newer types of CPP. Currently, activable CPP and tumor-targeting peptide (TTP)-modified nanocarriers have shown dramatically superior cellular specific uptake, cytotoxicity, and tumor growth inhibition. In this review, we discuss recent advances in tumor-targeting strategies using CPPs and their limitations in tumor delivery systems. Special emphasis is given to activable CPPs and TTPs. Finally, we address the application of CPPs and/or TTPs in the delivery of plant-derived chemotherapeutic agents.

  19. Hybrid detection of target sequence DNA based on phosphorescence resonance energy transfer.

    Science.gov (United States)

    Miao, Yanming; Lv, Jinzhi; Yan, Guiqin

    2017-08-15

    The severe background fluorescence and scattering light of real biological samples or environmental samples largely reduce the sensitivity and accuracy of fluorescence resonance energy transfer sensors based on fluorescent quantum dots (QDs). To solve this problem, we designed a novel target sequence DNA biosensor based on phosphorescent resonance energy transfer (PRET). This sensor relied on Mn-doped ZnS (Mn-ZnS) room-temperature phosphorescence (RTP) QDs/poly-(diallyldimethylammonium chloride) (PDADMAC) nanocomposite (QDs + ) as the energy donor and the single-strand DNA-ROX as the energy receptor. Thereby, an RTP biosensor was built and used to quantitatively detect target sequence DNA. This biosensor had a detection limit of 0.16nM and a linear range of 0.5-20nM for target sequence DNA. The dependence on RTP of QDs effectively avoided the interference from background fluorescence and scattering light in biological samples. Moreover, this sensor did not need sample pretreatment. Thus, this sensor compared with FRET is more feasible for quantitative detection of target sequence DNA in biological samples. Interestingly, the QDs + nanocomposite prolonged the phosphorescence lifetime of Mn-ZnS QDs by 2.6 times to 4.94ms, which was 5-6 magnitude-order larger than that of fluorescent QDs. Thus, this sensor largely improves the optical properties of QDs and permits chemical reactions at a long enough time scale. Copyright © 2017 Elsevier B.V. All rights reserved.

  20. A Rapid Python-Based Methodology for Target-Focused Combinatorial Library Design.

    Science.gov (United States)

    Li, Shiliang; Song, Yuwei; Liu, Xiaofeng; Li, Honglin

    2016-01-01

    The chemical space is so vast that only a small portion of it has been examined. As a complementary approach to systematically probe the chemical space, virtual combinatorial library design has extended enormous impacts on generating novel and diverse structures for drug discovery. Despite the favorable contributions, high attrition rates in drug development that mainly resulted from lack of efficacy and side effects make it increasingly challenging to discover good chemical starting points. In most cases, focused libraries, which are restricted to particular regions of the chemical space, are deftly exploited to maximize hit rate and improve efficiency at the beginning of the drug discovery and drug development pipeline. This paper presented a valid methodology for fast target-focused combinatorial library design in both reaction-based and production-based ways with the library creating rates of approximately 70,000 molecules per second. Simple, quick and convenient operating procedures are the specific features of the method. SHAFTS, a hybrid 3D similarity calculation software, was embedded to help refine the size of the libraries and improve hit rates. Two target-focused (p38-focused and COX2-focused) libraries were constructed efficiently in this study. This rapid library enumeration method is portable and applicable to any other targets for good chemical starting points identification collaborated with either structure-based or ligand-based virtual screening.

  1. A comparative study of SMILES-based compound similarity functions for drug-target interaction prediction.

    Science.gov (United States)

    Öztürk, Hakime; Ozkirimli, Elif; Özgür, Arzucan

    2016-03-18

    Molecular structures can be represented as strings of special characters using SMILES. Since each molecule is represented as a string, the similarity between compounds can be computed using SMILES-based string similarity functions. Most previous studies on drug-target interaction prediction use 2D-based compound similarity kernels such as SIMCOMP. To the best of our knowledge, using SMILES-based similarity functions, which are computationally more efficient than the 2D-based kernels, has not been investigated for this task before. In this study, we adapt and evaluate various SMILES-based similarity methods for drug-target interaction prediction. In addition, inspired by the vector space model of Information Retrieval we propose cosine similarity based SMILES kernels that make use of the Term Frequency (TF) and Term Frequency-Inverse Document Frequency (TF-IDF) weighting approaches. We also investigate generating composite kernels by combining our best SMILES-based similarity functions with the SIMCOMP kernel. With this study, we provided a comparison of 13 different ligand similarity functions, each of which utilizes the SMILES string of molecule representation. Additionally, TF and TF-IDF based cosine similarity kernels are proposed. The more efficient SMILES-based similarity functions performed similarly to the more complex 2D-based SIMCOMP kernel in terms of AUC-ROC scores. The TF-IDF based cosine similarity obtained a better AUC-PR score than the SIMCOMP kernel on the GPCR benchmark data set. The composite kernel of TF-IDF based cosine similarity and SIMCOMP achieved the best AUC-PR scores for all data sets.

  2. Target Detection of Quantum Illumination Receiver Based on Photon-subtracted Entanglement State

    Science.gov (United States)

    Chi, Jiao; Liu, HongJun; Huang, Nan; Wang, ZhaoLu

    2017-12-01

    We theoretically propose a quantum illumination receiver based on the ideal photon-subtracted two-mode squeezed state (PSTMSS) to efficiently detect the noise-hidden target. This receiver is generated by applying an optical parametric amplifier (OPA) to the cross correlation detection. With analyzing the output performance, it is found that OPA as a preposition technology of the receiver can contribute to the PSTMSS by significantly reducing the error probability than that of the general two-mode squeezed state (TMSS). Comparing with TMSS, the signal-to-noise ratio of quantum illumination based on ideal PSTMSS and OPA is improved more than 4 dB under an optimal gain of OPA. This work may provide a potential improvement in the application of accurate target detection when two kinds of resource have the identical real squeezing parameter.

  3. Expression study of the target receptor tyrosine kinase of Imatinib mesylate in skull base chordomas.

    Science.gov (United States)

    Orzan, Francesca; Terreni, Maria Rosa; Longoni, Mauro; Boari, Nicola; Mortini, Pietro; Doglioni, Claudio; Riva, Paola

    2007-07-01

    Chordomas are rare neoplasms arising along the axial skeleton. Up to now, the most suitable therapeutic approach is based on a combination of surgical excision and radiotherapy. Chemotherapy in not applied due to its reported low efficacy. Recently, evidence on the efficacy of Imatinib mesylate in two patients has been reported. We analyzed 14 chordoma samples for the expression of the Imatinib mesylate targets by means of RT-PCR and immunohistochemistry and found that PDGFR alpha and PDGFR beta are in some cases expressed in neoplastic cells, while the stromal counterpart of the same tumor shows the above receptors. Findings on the PDGFA/PDGFB expression suggest a receptor-activated status. Our study provides new insights into the specific localization of Imatinib mesylate targets in skull base chordomas that could be taken into account for the setting up of a pharmacological treatment for this tumor.

  4. Methodological Approach to Company Cash Flows Target-Oriented Forecasting Based on Financial Position Analysis

    OpenAIRE

    Sergey Krylov

    2012-01-01

    The article treats a new methodological approach to the company cash flows target-oriented forecasting based on its financial position analysis. The approach is featured to be universal and presumes application of the following techniques developed by the author: financial ratio values correction techniques and correcting cash flows techniques. The financial ratio values correction technique assumes to analyze and forecast company financial position while the correcting cash flows technique i...

  5. PITT: pronuclear injection-based targeted transgenesis, a reliable transgene expression method in mice.

    Science.gov (United States)

    Ohtsuka, Masato; Miura, Hiromi; Sato, Masahiro; Kimura, Minoru; Inoko, Hidetoshi; Gurumurthy, Channabasavaiah B

    2012-01-01

    Transgenic (Tg) mice have been extensively used as valuable tools for analyses of gene function and have also served as models for many human diseases. Typically, a transgenic mouse is created by microinjection of DNA into pronuclei in which the DNA gets integrated at random locations in the genome. Frequently however, the random integration of multiple copies of a transgene results in transgene silencing, probably because of a positional effect and/or repeat-induced gene silencing. The transgene silencing issue has been overcome by single-copy transgene integration into a predetermined locus through ES cell-mediated transgenesis, despite it being expensive and more time-consuming compared with pronuclear injection (PI)-mediated transgenesis. Recently, several groups have reported novel approaches that employ PI for targeted transgenesis. They are based on site-specific recombination catalyzed by a recombinase or an integrase or homologous recombination enhanced by a zinc-finger nuclease via PI. These next-generation transgenesis methods, which we termed as PI-based Targeted Transgenesis (PITT), are more convenient and faster than ES cell-based transgenesis. Furthermore, the Tg mice generated by these newer methods contain a single-copy transgene and exhibit reliable expression of the transgene. The objective of this review is to present the recent progress in mouse targeted transgenesis.

  6. A target based approach identifies genomic predictors of breast cancer patient response to chemotherapy

    Directory of Open Access Journals (Sweden)

    Hallett Robin M

    2012-05-01

    Full Text Available Abstract Background The efficacy of chemotherapy regimens in breast cancer patients is variable and unpredictable. Whether individual patients either achieve long-term remission or suffer recurrence after therapy may be dictated by intrinsic properties of their breast tumors including genetic lesions and consequent aberrant transcriptional programs. Global gene expression profiling provides a powerful tool to identify such tumor-intrinsic transcriptional programs, whose analyses provide insight into the underlying biology of individual patient tumors. For example, multi-gene expression signatures have been identified that can predict the likelihood of disease reccurrence, and thus guide patient prognosis. Whereas such prognostic signatures are being introduced in the clinical setting, similar signatures that predict sensitivity or resistance to chemotherapy are not currently clinically available. Methods We used gene expression profiling to identify genes that were co-expressed with genes whose transcripts encode the protein targets of commonly used chemotherapeutic agents. Results Here, we present target based expression indices that predict breast tumor response to anthracycline and taxane based chemotherapy. Indeed, these signatures were independently predictive of chemotherapy response after adjusting for standard clinic-pathological variables such as age, grade, and estrogen receptor status in a cohort of 488 breast cancer patients treated with adriamycin and taxotere/taxol. Conclusions Importantly, our findings suggest the practicality of developing target based indices that predict response to therapeutics, as well as highlight the possibility of using gene signatures to guide the use of chemotherapy during treatment of breast cancer patients.

  7. Multi-UAV Doppler Information Fusion for Target Tracking Based on Distributed High Degrees Information Filters

    Directory of Open Access Journals (Sweden)

    Hamza Benzerrouk

    2018-03-01

    Full Text Available Multi-Unmanned Aerial Vehicle (UAV Doppler-based target tracking has not been widely investigated, specifically when using modern nonlinear information filters. A high-degree Gauss–Hermite information filter, as well as a seventh-degree cubature information filter (CIF, is developed to improve the fifth-degree and third-degree CIFs proposed in the most recent related literature. These algorithms are applied to maneuvering target tracking based on Radar Doppler range/range rate signals. To achieve this purpose, different measurement models such as range-only, range rate, and bearing-only tracking are used in the simulations. In this paper, the mobile sensor target tracking problem is addressed and solved by a higher-degree class of quadrature information filters (HQIFs. A centralized fusion architecture based on distributed information filtering is proposed, and yielded excellent results. Three high dynamic UAVs are simulated with synchronized Doppler measurement broadcasted in parallel channels to the control center for global information fusion. Interesting results are obtained, with the superiority of certain classes of higher-degree quadrature information filters.

  8. General Quantum Meet-in-the-Middle Search Algorithm Based on Target Solution of Fixed Weight

    Science.gov (United States)

    Fu, Xiang-Qun; Bao, Wan-Su; Wang, Xiang; Shi, Jian-Hong

    2016-10-01

    Similar to the classical meet-in-the-middle algorithm, the storage and computation complexity are the key factors that decide the efficiency of the quantum meet-in-the-middle algorithm. Aiming at the target vector of fixed weight, based on the quantum meet-in-the-middle algorithm, the algorithm for searching all n-product vectors with the same weight is presented, whose complexity is better than the exhaustive search algorithm. And the algorithm can reduce the storage complexity of the quantum meet-in-the-middle search algorithm. Then based on the algorithm and the knapsack vector of the Chor-Rivest public-key crypto of fixed weight d, we present a general quantum meet-in-the-middle search algorithm based on the target solution of fixed weight, whose computational complexity is \\sumj = 0d {(O(\\sqrt {Cn - k + 1d - j }) + O(C_kj log C_k^j))} with Σd i =0 Ck i memory cost. And the optimal value of k is given. Compared to the quantum meet-in-the-middle search algorithm for knapsack problem and the quantum algorithm for searching a target solution of fixed weight, the computational complexity of the algorithm is lower. And its storage complexity is smaller than the quantum meet-in-the-middle-algorithm. Supported by the National Basic Research Program of China under Grant No. 2013CB338002 and the National Natural Science Foundation of China under Grant No. 61502526

  9. Micro-motion Recognition of Spatial Cone Target Based on ISAR Image Sequences

    Directory of Open Access Journals (Sweden)

    Changyong Shu

    2016-04-01

    Full Text Available The accurate micro-motions recognition of spatial cone target is the foundation of the characteristic parameter acquisition. For this reason, a micro-motion recognition method based on the distinguishing characteristics extracted from the Inverse Synthetic Aperture Radar (ISAR sequences is proposed in this paper. The projection trajectory formula of cone node strong scattering source and cone bottom slip-type strong scattering sources, which are located on the spatial cone target, are deduced under three micro-motion types including nutation, precession, and spinning, and the correctness is verified by the electromagnetic simulation. By comparison, differences are found among the projection of the scattering sources with different micro-motions, the coordinate information of the scattering sources in the Inverse Synthetic Aperture Radar sequences is extracted by the CLEAN algorithm, and the spinning is recognized by setting the threshold value of Doppler. The double observation points Interacting Multiple Model Kalman Filter is used to separate the scattering sources projection of the nutation target or precession target, and the cross point number of each scattering source’s projection track is used to classify the nutation or precession. Finally, the electromagnetic simulation data are used to verify the effectiveness of the micro-motion recognition method.

  10. Hi-Plex for Simple, Accurate, and Cost-Effective Amplicon-based Targeted DNA Sequencing.

    Science.gov (United States)

    Pope, Bernard J; Hammet, Fleur; Nguyen-Dumont, Tu; Park, Daniel J

    2018-01-01

    Hi-Plex is a suite of methods to enable simple, accurate, and cost-effective highly multiplex PCR-based targeted sequencing (Nguyen-Dumont et al., Biotechniques 58:33-36, 2015). At its core is the principle of using gene-specific primers (GSPs) to "seed" (or target) the reaction and universal primers to "drive" the majority of the reaction. In this manner, effects on amplification efficiencies across the target amplicons can, to a large extent, be restricted to early seeding cycles. Product sizes are defined within a relatively narrow range to enable high-specificity size selection, replication uniformity across target sites (including in the context of fragmented input DNA such as that derived from fixed tumor specimens (Nguyen-Dumont et al., Biotechniques 55:69-74, 2013; Nguyen-Dumont et al., Anal Biochem 470:48-51, 2015), and application of high-specificity genetic variant calling algorithms (Pope et al., Source Code Biol Med 9:3, 2014; Park et al., BMC Bioinformatics 17:165, 2016). Hi-Plex offers a streamlined workflow that is suitable for testing large numbers of specimens without the need for automation.

  11. A local contrast based approach to threshold segmentation for PET target volume delineation

    International Nuclear Information System (INIS)

    Drever, Laura; Robinson, Don M.; McEwan, Alexander; Roa, Wilson

    2006-01-01

    Current radiation therapy techniques, such as intensity modulated radiation therapy and three-dimensional conformal radiotherapy rely on the precise delivery of high doses of radiation to well-defined volumes. CT, the imaging modality that is most commonly used to determine treatment volumes cannot, however, easily distinguish between cancerous and normal tissue. The ability of positron emission tomography (PET) to more readily differentiate between malignant and healthy tissues has generated great interest in using PET images to delineate target volumes for radiation treatment planning. At present the accurate geometric delineation of tumor volumes is a subject open to considerable interpretation. The possibility of using a local contrast based approach to threshold segmentation to accurately delineate PET target cross sections is investigated using well-defined cylindrical and spherical volumes. Contrast levels which yield correct volumetric quantification are found to be a function of the activity concentration ratio between target and background, target size, and slice location. Possibilities for clinical implementation are explored along with the limits posed by this form of segmentation

  12. Radar Target Detection Method of Aircraft Wake Vortices Based on Matrix Information Geometry

    Directory of Open Access Journals (Sweden)

    Liu Junkai

    2017-12-01

    Full Text Available The application of matrix information geometry to radar signal processing and target detection is a new and interesting subject. Wake vortices are Doppler-spread after Fourier transform. The traditional Moving Target Detection (MTD method cannot adequately accumulate returns power of the whole spectrum. Based on matrix information geometry, a matrix Constant False Alarm Rate (CFAR detection method is proposed to improve the detection performance of a weak wake target. In this method, covariance matrices of the observed data can be constructed into a matrix manifold; compared with CFAR detection, the geodesic distance between the covariance matrix in the detection cell and the mean of covariance matrices in the secondary cell is regarded as the detection statistics. Using simulated wake vortices, the return data in background noise and the iterative estimation performance of Riemannian mean are analyzed; the geodesic distance of covariance matrices of target return and noise with varying signal-noise rate is analyzed; and the detection performance of the matrix CFAR and the conventional MTD method is compared.

  13. Analysis on Target Detection and Classification in LTE Based Passive Forward Scattering Radar.

    Science.gov (United States)

    Raja Abdullah, Raja Syamsul Azmir; Abdul Aziz, Noor Hafizah; Abdul Rashid, Nur Emileen; Ahmad Salah, Asem; Hashim, Fazirulhisyam

    2016-09-29

    The passive bistatic radar (PBR) system can utilize the illuminator of opportunity to enhance radar capability. By utilizing the forward scattering technique and procedure into the specific mode of PBR can provide an improvement in target detection and classification. The system is known as passive Forward Scattering Radar (FSR). The passive FSR system can exploit the peculiar advantage of the enhancement in forward scatter radar cross section (FSRCS) for target detection. Thus, the aim of this paper is to show the feasibility of passive FSR for moving target detection and classification by experimental analysis and results. The signal source is coming from the latest technology of 4G Long-Term Evolution (LTE) base station. A detailed explanation on the passive FSR receiver circuit, the detection scheme and the classification algorithm are given. In addition, the proposed passive FSR circuit employs the self-mixing technique at the receiver; hence the synchronization signal from the transmitter is not required. The experimental results confirm the passive FSR system's capability for ground target detection and classification. Furthermore, this paper illustrates the first classification result in the passive FSR system. The great potential in the passive FSR system provides a new research area in passive radar that can be used for diverse remote monitoring applications.

  14. Intercept Algorithm for Maneuvering Targets Based on Differential Geometry and Lyapunov Theory

    Directory of Open Access Journals (Sweden)

    Yunes Sh. ALQUDSI

    2018-03-01

    Full Text Available Nowadays, the homing guidance is utilized in the existed and under development air defense systems (ADS to effectively intercept the targets. The targets became smarter and capable to fly and maneuver professionally and the tendency to design missile with a small warhead became greater, then there is a pressure to produce a more precise and accurate missile guidance system based on intelligent algorithms to ensure effective interception of highly maneuverable targets. The aim of this paper is to present an intelligent guidance algorithm that effectively and precisely intercept the maneuverable and smart targets by virtue of the differential geometry (DG concepts. The intercept geometry and engagement kinematics, in addition to the direct intercept condition are developed and expressed in DG terms. The guidance algorithm is then developed by virtue of DG and Lyapunov theory. The study terminates with 2D engagement simulation with illustrative examples, to demonstrate that, the derived DG guidance algorithm is a generalized guidance approach and the well-known proportional navigation (PN guidance law is a subset of this approach.

  15. Multiple-Targeted Graphene-based Nanocarrier for Intracellular Imaging of mRNAs

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ying; Li, Zhaohui; Liu, Misha; Hu, Dehong; Lin, Yuehe; Li, Jinghong

    2017-08-29

    Simultaneous detection and imaging of multiple intracellular messenger RNA (mRNAs) hold great significant for early cancer diagnostics and preventive medicine development. Herein, we propose a multiple-targeted graphene oxide (GO) nanocarrier that can simultaneously detect and image different type mRNAs in living cells. First of all, in vitro detection of multiple targets have been realized successfully based on the multiple-targeted GO nanocarrier with linear relationship ranging from 3 nM to 200 nM, as well as sensitive detection limit of 1.84 nM for manganese superoxide dismutase (Mn-SOD) mRNA and 2.45 nM for β-actin mRNA. Additionally, this nanosensing platform composed of fluorescent labeled single strand DNA probes and GO nanocarrier can identify Mn-SOD mRNA and endogenous mRNA of β-actin in living cancer cells, showing rapid response, high specificity, nuclease stability, and good biocompatibility during the cell imaging. Thirdly, changes of the expression levels of mRNA in living cells before or after the drug treatment can be monitored successfully. By using multiple ssDNA as probes and GO nanocarrier as the cellular delivery cargo, the proposed simultaneous multiple-targeted sensing platform will be of great potential as a powerful tool for intracellular trafficking process from basic research to clinical diagnosis.

  16. UPAR targeted molecular imaging of cancers with small molecule-based probes.

    Science.gov (United States)

    Ding, Feng; Chen, Seng; Zhang, Wanshu; Tu, Yufeng; Sun, Yao

    2017-10-15

    Molecular imaging can allow the non-invasive characterization and measurement of biological and biochemical processes at the molecular and cellular levels in living subjects. The imaging of specific molecular targets that are associated with cancers could allow for the earlier diagnosis and better treatment of diseases. Small molecule-based probes play prominent roles in biomedical research and have high clinical translation ability. Here, with an emphasis on small molecule-based probes, we review some recent developments in biomarkers, imaging techniques and multimodal imaging in molecular imaging and highlight the successful applications for molecular imaging of cancers. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. Characterization of background noise in capture-based targeted sequencing data.

    Science.gov (United States)

    Park, Gahee; Park, Joo Kyung; Shin, Seung-Ho; Jeon, Hyo-Jeong; Kim, Nayoung K D; Kim, Yeon Jeong; Shin, Hyun-Tae; Lee, Eunjin; Lee, Kwang Hyuck; Son, Dae-Soon; Park, Woong-Yang; Park, Donghyun

    2017-07-21

    Targeted deep sequencing is increasingly used to detect low-allelic fraction variants; it is therefore essential that errors that constitute baseline noise and impose a practical limit on detection are characterized. In the present study, we systematically evaluate the extent to which errors are incurred during specific steps of the capture-based targeted sequencing process. We removed most sequencing artifacts by filtering out low-quality bases and then analyze the remaining background noise. By recognizing that plasma DNA is naturally fragmented to be of a size comparable to that of mono-nucleosomal DNA, we were able to identify and characterize errors that are specifically associated with acoustic shearing. Two-thirds of C:G > A:T errors and one quarter of C:G > G:C errors were attributed to the oxidation of guanine during acoustic shearing, and this was further validated by comparative experiments conducted under different shearing conditions. The acoustic shearing step also causes A > G and A > T substitutions localized to the end bases of sheared DNA fragments, indicating a probable association of these errors with DNA breakage. Finally, the hybrid selection step contributes to one-third of the remaining C:G > A:T and one-fifth of the C > T errors. The results of this study provide a comprehensive summary of various errors incurred during targeted deep sequencing, and their underlying causes. This information will be invaluable to drive technical improvements in this sequencing method, and may increase the future usage of targeted deep sequencing methods for low-allelic fraction variant detection.

  18. Development of antibody-based c-Met inhibitors for targeted cancer therapy

    Directory of Open Access Journals (Sweden)

    Lee D

    2015-02-01

    Full Text Available Dongheon Lee, Eun-Sil Sung, Jin-Hyung Ahn, Sungwon An, Jiwon Huh, Weon-Kyoo You Hanwha Chemical R&D Center, Biologics Business Unit, Daejeon, Republic of Korea Abstract: Signaling pathways mediated by receptor tyrosine kinases (RTKs and their ligands play important roles in the development and progression of human cancers, which makes RTK-mediated signaling pathways promising therapeutic targets in the treatment of cancer. Compared with small-molecule compounds, antibody-based therapeutics can more specifically recognize and bind to ligands and RTKs. Several antibody inhibitors of RTK-mediated signaling pathways, such as human epidermal growth factor receptor 2, vascular endothelial growth factor, epidermal growth factor receptor or vascular endothelial growth factor receptor 2, have been developed and are widely used to treat cancer patients. However, since the therapeutic options are still limited in terms of therapeutic efficacy and types of cancers that can be treated, efforts are being made to identify and evaluate novel RTK-mediated signaling pathways as targets for more efficacious cancer treatment. The hepatocyte growth factor/c-Met signaling pathway has come into the spotlight as a promising target for development of potent cancer therapeutic agents. Multiple antibody-based therapeutics targeting hepatocyte growth factor or c-Met are currently in preclinical or clinical development. This review focuses on the development of inhibitors of the hepatocyte growth factor/c-Met signaling pathway for cancer treatment, including critical issues in clinical development and future perspectives for antibody-based therapeutics. Keywords: hepatocyte growth factor, ligands, receptor tyrosine kinase, signaling pathway, therapeutic agent

  19. Daily ultrasound-based image-guided targeting for radiotherapy of upper abdominal malignancies.

    Science.gov (United States)

    Fuss, Martin; Salter, Bill J; Cavanaugh, Sean X; Fuss, Cristina; Sadeghi, Amir; Fuller, Clifton D; Ameduri, Ardow; Hevezi, James M; Herman, Terence S; Thomas, Charles R

    2004-07-15

    Development and implementation of a strategy to use a stereotactic ultrasound (US)-based image-guided targeting device (BAT) to align intensity-modulated radiotherapy (IMRT) target volumes accurately in the upper abdomen. Because the outlines of such targets may be poorly visualized by US, we present a method that uses adjacent vascular guidance structures as surrogates for the target position. We assessed the potential for improvement of daily repositioning and the feasibility of daily application. A total of 62 patients were treated by sequential tomotherapeutic IMRT between October 2000 and June 2003 for cholangiocarcinoma and gallbladder carcinoma (n = 10), hepatocellular carcinoma (n = 10), liver metastases (n = 11), pancreatic carcinoma (n = 20), neuroblastoma (n = 3), and other abdominal and retroperitoneal tumors (n = 8). The target volumes (TVs) and organs at risk were delineated in contrast-enhanced CT data sets. Additionally, vascular guidance structures in close anatomic relation to the TV, or within the TV, were delineated. Throughout the course of IMRT, US BAT images were acquired during daily treatment positioning. In addition to the anatomic structures typically used for US targeting (e.g., the TV and dose-limiting organs at risk), CT contours of guidance structures were superimposed onto the real-time acquired axial and sagittal US images, and target position adjustments, as indicated by the system, were performed accordingly. We report the BAT-derived distribution of shifts in the three principal room axes compared with a skin-mark-based setup, as well as the time required to perform BAT alignment. The capability of the presented method to improve target alignment was assessed in 15 patients by comparing the organ and fiducial position between the respective treatment simulation CT with a control CT study after US targeting in the CT suite. A total of 1,337 BAT alignments were attempted. US images were not useful in 56 setups (4.2%), mainly

  20. Production and release of gas and volatile elements from sodium-based targets

    CERN Multimedia

    Plewinski, F; Wildner, E; Catherall, R

    Several large scale facilities being studied for Europe use sodium or a sodium-based alloy either as a target or as a coolant for heavier solid targets subjected to MW proton beams, such as the European Spallation Source (ESS) and $\\beta$-beam projects. ESS will be the neutron source in use from the year 2020 in Europe, providing high intensity neutron fluxes over large energy spectra ( from 10$^{-3}$ eV to 10$^{3}$ eV) to scientists, to explore materials from 10$^{-2}$m to 10$^{-16}$m scale. A sodium-cooled array of tungsten blocks is one of the potential solutions for the target that will convert protons from the 5 MW 2.5 GeV linac into neutrons. Sodium is a tried and tested coolant in fast nuclear reactors with associated technologies and design standards. Its application to a spallation environment however remains to be validated. The ISOLDE facility is well placed to perform detailed measurements of radioisotopes produced in sodium with a proton beam whose energy of 1.4 GeV is very close to the ESS base...

  1. Robotics Vision-based Heuristic Reasoning for Underwater Target Tracking and Navigation

    Directory of Open Access Journals (Sweden)

    Chua Kia

    2008-11-01

    Full Text Available This paper presents a robotics vision-based heuristic reasoning system for underwater target tracking and navigation. This system is introduced to improve the level of automation of underwater Remote Operated Vehicles (ROVs operations. A prototype which combines computer vision with an underwater robotics system is successfully designed and developed to perform target tracking and intelligent navigation. This study focuses on developing image processing algorithms and fuzzy inference system for the analysis of the terrain. The vision system developed is capable of interpreting underwater scene by extracting subjective uncertainties of the object of interest. Subjective uncertainties are further processed as multiple inputs of a fuzzy inference system that is capable of making crisp decisions concerning where to navigate. The important part of the image analysis is morphological filtering. The applications focus on binary images with the extension of gray-level concepts. An open-loop fuzzy control system is developed for classifying the traverse of terrain. The great achievement is the system's capability to recognize and perform target tracking of the object of interest (pipeline in perspective view based on perceived condition. The effectiveness of this approach is demonstrated by computer and prototype simulations. This work is originated from the desire to develop robotics vision system with the ability to mimic the human expert's judgement and reasoning when maneuvering ROV in the traverse of the underwater terrain.

  2. A cell-based screen reveals that the albendazole metabolite, albendazole sulfone, targets Wolbachia.

    Directory of Open Access Journals (Sweden)

    Laura R Serbus

    2012-09-01

    Full Text Available Wolbachia endosymbionts carried by filarial nematodes give rise to the neglected diseases African river blindness and lymphatic filariasis afflicting millions worldwide. Here we identify new Wolbachia-disrupting compounds by conducting high-throughput cell-based chemical screens using a Wolbachia-infected, fluorescently labeled Drosophila cell line. This screen yielded several Wolbachia-disrupting compounds including three that resembled Albendazole, a widely used anthelmintic drug that targets nematode microtubules. Follow-up studies demonstrate that a common Albendazole metabolite, Albendazole sulfone, reduces intracellular Wolbachia titer both in Drosophila melanogaster and Brugia malayi, the nematode responsible for lymphatic filariasis. Significantly, Albendazole sulfone does not disrupt Drosophila microtubule organization, suggesting that this compound reduces titer through direct targeting of Wolbachia. Accordingly, both DNA staining and FtsZ immunofluorescence demonstrates that Albendazole sulfone treatment induces Wolbachia elongation, a phenotype indicative of binary fission defects. This suggests that the efficacy of Albendazole in treating filarial nematode-based diseases is attributable to dual targeting of nematode microtubules and their Wolbachia endosymbionts.

  3. Three-Dimensional Precession Feature Extraction of Ballistic Targets Based on Narrowband Radar Network

    Directory of Open Access Journals (Sweden)

    Zhao Shuang

    2017-02-01

    Full Text Available Micro-motion is a crucial feature used in ballistic target recognition. To address the problem that single-view observations cannot extract true micro-motion parameters, we propose a novel algorithm based on the narrowband radar network to extract three-dimensional precession features. First, we construct a precession model of the cone-shaped target, and as a precondition, we consider the invisible problem of scattering centers. We then analyze in detail the micro-Doppler modulation trait caused by the precession. Then, we match each scattering center in different perspectives based on the ratio of the top scattering center’s micro-Doppler frequency modulation coefficient and extract the 3D coning vector of the target by establishing associated multi-aspect equation systems. In addition, we estimate feature parameters by utilizing the correlation of the micro-Doppler frequency modulation coefficient of the three scattering centers combined with the frequency compensation method. We then calculate the coordinates of the conical point in each moment and reconstruct the 3D spatial portion. Finally, we provide simulation results to validate the proposed algorithm.

  4. G-quadruplex-based aptamers against protein targets in therapy and diagnostics.

    Science.gov (United States)

    Platella, Chiara; Riccardi, Claudia; Montesarchio, Daniela; Roviello, Giovanni N; Musumeci, Domenica

    2017-05-01

    Nucleic acid aptamers are single-stranded DNA or RNA molecules identified to recognize with high affinity specific targets including proteins, small molecules, ions, whole cells and even entire organisms, such as viruses or bacteria. They can be identified from combinatorial libraries of DNA or RNA oligonucleotides by SELEX technology, an in vitro iterative selection procedure consisting of binding (capture), partitioning and amplification steps. Remarkably, many of the aptamers selected against biologically relevant protein targets are G-rich sequences that can fold into stable G-quadruplex (G4) structures. Aiming at disseminating novel inspiring ideas within the scientific community in the field of G4-structures, the emphasis of this review is placed on: 1) recent advancements in SELEX technology for the efficient and rapid identification of new candidate aptamers (introduction of microfluidic systems and next generation sequencing); 2) recurrence of G4 structures in aptamers selected by SELEX against biologically relevant protein targets; 3) discovery of several G4-forming motifs in important regulatory regions of the human or viral genome bound by endogenous proteins, which per se can result into potential aptamers; 4) an updated overview of G4-based aptamers with therapeutic potential and 5) a discussion on the most attractive G4-based aptamers for diagnostic applications. This article is part of a Special Issue entitled "G-quadruplex" Guest Editor: Dr. Concetta Giancola and Dr. Daniela Montesarchio. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Estimation of direction of arrival of a moving target using subspace based approaches

    Science.gov (United States)

    Ghosh, Ripul; Das, Utpal; Akula, Aparna; Kumar, Satish; Sardana, H. K.

    2016-05-01

    In this work, array processing techniques based on subspace decomposition of signal have been evaluated for estimation of direction of arrival of moving targets using acoustic signatures. Three subspace based approaches - Incoherent Wideband Multiple Signal Classification (IWM), Least Square-Estimation of Signal Parameters via Rotation Invariance Techniques (LS-ESPRIT) and Total Least Square- ESPIRIT (TLS-ESPRIT) are considered. Their performance is compared with conventional time delay estimation (TDE) approaches such as Generalized Cross Correlation (GCC) and Average Square Difference Function (ASDF). Performance evaluation has been conducted on experimentally generated data consisting of acoustic signatures of four different types of civilian vehicles moving in defined geometrical trajectories. Mean absolute error and standard deviation of the DOA estimates w.r.t. ground truth are used as performance evaluation metrics. Lower statistical values of mean error confirm the superiority of subspace based approaches over TDE based techniques. Amongst the compared methods, LS-ESPRIT indicated better performance.

  6. Petri net-based prediction of therapeutic targets that recover abnormally phosphorylated proteins in muscle atrophy.

    Science.gov (United States)

    Jung, Jinmyung; Kwon, Mijin; Bae, Sunghwa; Yim, Soorin; Lee, Doheon

    2018-03-05

    Muscle atrophy, an involuntary loss of muscle mass, is involved in various diseases and sometimes leads to mortality. However, therapeutics for muscle atrophy thus far have had limited effects. Here, we present a new approach for therapeutic target prediction using Petri net simulation of the status of phosphorylation, with a reasonable assumption that the recovery of abnormally phosphorylated proteins can be a treatment for muscle atrophy. The Petri net model was employed to simulate phosphorylation status in three states, i.e. reference, atrophic and each gene-inhibited state based on the myocyte-specific phosphorylation network. Here, we newly devised a phosphorylation specific Petri net that involves two types of transitions (phosphorylation or de-phosphorylation) and two types of places (activation with or without phosphorylation). Before predicting therapeutic targets, the simulation results in reference and atrophic states were validated by Western blotting experiments detecting five marker proteins, i.e. RELA, SMAD2, SMAD3, FOXO1 and FOXO3. Finally, we determined 37 potential therapeutic targets whose inhibition recovers the phosphorylation status from an atrophic state as indicated by the five validated marker proteins. In the evaluation, we confirmed that the 37 potential targets were enriched for muscle atrophy-related terms such as actin and muscle contraction processes, and they were also significantly overlapping with the genes associated with muscle atrophy reported in the Comparative Toxicogenomics Database (p-value net. We generated a list of the potential therapeutic targets whose inhibition recovers abnormally phosphorylated proteins in an atrophic state. They were evaluated by various approaches, such as Western blotting, GO terms, literature, known muscle atrophy-related genes and shortest path analysis. We expect the new proposed strategy to provide an understanding of phosphorylation status in muscle atrophy and to provide assistance towards

  7. Ballistic Target PHD Filter Based on Infrared Focal Plane Ambiguous Observation

    Directory of Open Access Journals (Sweden)

    Wei Zhao

    2017-01-01

    Full Text Available Space-based early warning system, the main detection means of which is passive detection based on focal plane, is an important part of ballistic missile defense system. The focal plane is mainly composed of CCD, and its size can reach the micron level, so the pixel is often regarded as point of no area in image postprocessing. The design of traditional tracking methods is based on this, and the observation based on the focal plane is modeled as the azimuth with random noise. However, this modeling is inaccurate. In the context of space-based detection, CCD cannot be simplified as a point, and its size should be considered. And the corresponding observation cannot be treated as azimuth with random noise. In this paper, the observation based on focal plane is modeled as Unambiguously Generated Ambiguous (UGA measurement. The PHD filter algorithm is redesigned and simplified. The simulation results show that the algorithm based on UGA measurement observation model has better tracking effect compared with that based on traditional observation model. This method provides technical support for more accurate target tracking for space-based early warning system.

  8. Development and optimization of targeted radionuclide tumor therapy using folate based radiopharmaceuticals

    CERN Document Server

    Reber, Josefine Astrid

    The folate receptor (FR) has been used for a quarter of a century as a tumor-associated target for selective delivery of drugs and imaging agents to cancer cells. While several folic acid radioconjugates have been successfully employed for imaging purposes in (pre)clinical studies, a therapeutic application of folic acid radioconjugates has not yet reached the critical stage which would allow a clinical translation. Due to a substantial expression of the FR in the proximal tubule cells, radiofolates accumulate in the kidneys which are at risk of damage by particle-radiation. To improve this situation, we aimed to develop and evaluate strategies for the performance of FR-targeted radionuclide therapy by decreasing the renal uptake of radiofolates and thereby reducing potential nephrotoxic effects. Two different strategies were investigated. First, the combination of radiofolates with chemotherapeutic agents such as pemetrexed (PMX) and 5-fluorouracil (5-FU) and secondly, an approach based on radioiodinated fol...

  9. Water based suspensions of iron oxide obtained by laser target evaporation for biomedical applications

    Energy Technology Data Exchange (ETDEWEB)

    Novoselova, I.P. [Ural Federal University, Department of Magnetism and Magnetic Nanomaterials, Lenin Ave. 51, 620083 Yekaterinburg (Russian Federation); Immanuel Kant Baltic Federal University, Science and Technology Park “Fabrica”, Gaidara St. 6, 236022 Kaliningrad (Russian Federation); Safronov, A.P. [Ural Federal University, Department of Magnetism and Magnetic Nanomaterials, Lenin Ave. 51, 620083 Yekaterinburg (Russian Federation); Institute of Electrophysics UD RAS, Amundsena St. 106, 620016 Yekaterinburg (Russian Federation); Samatov, O.M. [Institute of Electrophysics UD RAS, Amundsena St. 106, 620016 Yekaterinburg (Russian Federation); Beketov, I.V.; Medvedev, A.I. [Ural Federal University, Department of Magnetism and Magnetic Nanomaterials, Lenin Ave. 51, 620083 Yekaterinburg (Russian Federation); Institute of Electrophysics UD RAS, Amundsena St. 106, 620016 Yekaterinburg (Russian Federation); Kurlyandskaya, G.V. [Ural Federal University, Department of Magnetism and Magnetic Nanomaterials, Lenin Ave. 51, 620083 Yekaterinburg (Russian Federation); Universidad del País Vasco, UPV/EHU, Dpto. de Electricidad y Electrónica, P.O. Box 644, Bilbao 48080 (Spain)

    2016-10-01

    In this work spherical magnetic nanoparticles (MNPs) of iron oxide were obtained by laser target evaporation technique (LTE). Water based suspensions were prepared on the basis of obtained MNPs and their properties were also studied including inductive heat capacity. Their structure and properties were studied by a number of techniques including magnetometry and heat capacity measurements. Magnetic induction heating experiment show the specific loss power (SLP) value in the narrow range from 1.30 to 1.45 W/g for all samples under consideration when using alternating magnetic field of 1.7 kA/m and frequency of 210 kHz. These parameters insure that LTE MNPs are interesting materials promising for magnetic fluid hyperthermia. - Highlights: • Spheric oxide nanoparticles obtained by productive laser target evaporation method. • Experiment shows the specific loss power value in the narrow range for all samples. • Obtained results insure these objects as interesting material for hyperthermia.

  10. Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods.

    Science.gov (United States)

    Hoak, Anthony; Medeiros, Henry; Povinelli, Richard J

    2017-03-03

    We develop an interactive likelihood (ILH) for sequential Monte Carlo (SMC) methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL) and TUD-Stadtmitte) using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA) and classification of events, activities and relationships for multi-object trackers (CLEAR MOT)). In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

  11. Image-Based Multi-Target Tracking through Multi-Bernoulli Filtering with Interactive Likelihoods

    Directory of Open Access Journals (Sweden)

    Anthony Hoak

    2017-03-01

    Full Text Available We develop an interactive likelihood (ILH for sequential Monte Carlo (SMC methods for image-based multiple target tracking applications. The purpose of the ILH is to improve tracking accuracy by reducing the need for data association. In addition, we integrate a recently developed deep neural network for pedestrian detection along with the ILH with a multi-Bernoulli filter. We evaluate the performance of the multi-Bernoulli filter with the ILH and the pedestrian detector in a number of publicly available datasets (2003 PETS INMOVE, Australian Rules Football League (AFL and TUD-Stadtmitte using standard, well-known multi-target tracking metrics (optimal sub-pattern assignment (OSPA and classification of events, activities and relationships for multi-object trackers (CLEAR MOT. In all datasets, the ILH term increases the tracking accuracy of the multi-Bernoulli filter.

  12. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    Energy Technology Data Exchange (ETDEWEB)

    Missailidis, Sotiris [The Open University, Milton Keynes (United Kingdom). Dept. of Chemistry and Analytical Sciences]. E-mail: s.missailidis@open.ac.uk; Perkins, Alan [University of Nottingham (United Kingdom). Dept. of Medical Physics; Santos-Filho, Sebastiao David; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario [Universidade do Estado do Rio de Janeiro (UERJ), RJ (Brazil). Inst. de Biologia Roberto Alcantara Gomes. Dept. de Biofisica e Biometria

    2008-12-15

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

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

    DEFF Research Database (Denmark)

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

    2013-01-01

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

  14. Biosafety research for non-target organism risk assessment of RNAi-based GE plants

    Science.gov (United States)

    Roberts, Andrew F.; Devos, Yann; Lemgo, Godwin N. Y.; Zhou, Xuguo

    2015-01-01

    RNA interference, or RNAi, refers to a set of biological processes that make use of conserved cellular machinery to silence genes. Although there are several variations in the source and mechanism, they are all triggered by double stranded RNA (dsRNA) which is processed by a protein complex into small, single stranded RNA, referred to as small interfering RNAs (siRNA) with complementarity to sequences in genes targeted for silencing. The use of the RNAi mechanism to develop new traits in plants has fueled a discussion about the environmental safety of the technology for these applications, and this was the subject of a symposium session at the 13th ISBGMO in Cape Town, South Africa. This paper continues that discussion by proposing research areas that may be beneficial for future environmental risk assessments of RNAi-based genetically modified plants, with a particular focus on non-target organism assessment. PMID:26594220

  15. Nanotechnology-based drug delivery treatments and specific targeting therapy for age-related macular degeneration

    Directory of Open Access Journals (Sweden)

    Tai-Chi Lin

    2015-11-01

    Full Text Available Nanoparticles combined with cells, drugs, and specially designed genes provide improved therapeutic efficacy in studies and clinical setting, demonstrating a new era of treatment strategy, especially in retinal diseases. Nanotechnology-based drugs can provide an essential platform for sustaining, releasing and a specific targeting design to treat retinal diseases. Poly-lactic-co-glycolic acid is the most widely used biocompatible and biodegradable polymer approved by the Food and Drug Administration. Many studies have attempted to develop special devices for delivering small-molecule drugs, proteins, and other macromolecules consistently and slowly. In this article, we first review current progress in the treatment of age-related macular degeneration. Then, we discuss the function of vascular endothelial growth factor (VEGF and the pharmacological effects of anti-VEGF-A antibodies and soluble or modified VEGF receptors. Lastly, we summarize the combination of antiangiogenic therapy and nanomedicines, and review current potential targeting therapy in age-related macular degeneration.

  16. Small target detection based on human visual system utilizing distance information

    Science.gov (United States)

    Yang, Linna; An, Wei; Lin, Zaiping; Li, Andong; Ye, Jundu

    2015-10-01

    Small target detection is an importance part of infrared technology. Human visual system properties can improve signal to noise rate and detection rate, etc. In this paper, a small target detection algorithm based on human visual system utilizing distance information is proposed. First, surrounding regions is calculated by weighed sum of each pixel in surrounding regions. The weight is related to distance information between each surrounding pixel and center pixel. Then, the contrast value of center pixel blocks and surrounding regions is calculated. Finally, the contrast value is weighted to the center pixel to get a saliency map. Experiment shows that the proposed has good performance on improving the signal to noise rate and detection rate.

  17. Water based suspensions of iron oxide obtained by laser target evaporation for biomedical applications

    International Nuclear Information System (INIS)

    Novoselova, I.P.; Safronov, A.P.; Samatov, O.M.; Beketov, I.V.; Medvedev, A.I.; Kurlyandskaya, G.V.

    2016-01-01

    In this work spherical magnetic nanoparticles (MNPs) of iron oxide were obtained by laser target evaporation technique (LTE). Water based suspensions were prepared on the basis of obtained MNPs and their properties were also studied including inductive heat capacity. Their structure and properties were studied by a number of techniques including magnetometry and heat capacity measurements. Magnetic induction heating experiment show the specific loss power (SLP) value in the narrow range from 1.30 to 1.45 W/g for all samples under consideration when using alternating magnetic field of 1.7 kA/m and frequency of 210 kHz. These parameters insure that LTE MNPs are interesting materials promising for magnetic fluid hyperthermia. - Highlights: • Spheric oxide nanoparticles obtained by productive laser target evaporation method. • Experiment shows the specific loss power value in the narrow range for all samples. • Obtained results insure these objects as interesting material for hyperthermia.

  18. Aptamer-based radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of epithelial tumors

    International Nuclear Information System (INIS)

    Missailidis, Sotiris; Perkins, Alan; Santos-Filho, Sebastiao David; Fonseca, Adenilson de Souza da; Bernardo-Filho, Mario

    2008-01-01

    In the continuous search for earlier diagnosis and improved therapeutic modalities against cancer, based on our constantly increasing knowledge of cancer biology, aptamers hold the promise to expand on current antibody success, but overcoming some of the problems faced with antibodies as therapeutic or delivery agents in cancer. However, as the first aptamer reached the market as an inhibitor against angiogenesis for the treatment of macular degeneration, aptamers have found only limited applications or interest in oncology, and even less as radiopharmaceuticals for diagnostic imaging and targeted radiotherapy of tumours. Yet, the chemistry for the labelling of aptamers and the options to alter their pharmacokinetic properties, to make them suitable for use as radiopharmaceuticals is now available and recent advances in their development can demonstrate that these molecules would make them ideal delivery vehicles for the development of targeted radiopharmaceuticals that could deliver their radiation load with accuracy to the tumour site, offering improved therapeutic properties and reduced side effects. (author)

  19. Color Doppler Ultrasonography-Targeted Perforator Mapping and Angiosome-Based Flap Reconstruction

    DEFF Research Database (Denmark)

    Gunnarsson, Gudjon Leifur; Tei, Troels; Thomsen, Jørn Bo

    2016-01-01

    Knowledge about perforators and angiosomes has inspired new and innovative flap designs for reconstruction of defects throughout the body. The purpose of this article is to share our experience using color Doppler ultrasonography (CDU)-targeted perforator mapping and angiosome-based flap...... reconstruction throughout the body. The CDU was used to identify the largest and best-located perforator adjacent to the defect to target the reconstruction. The cutaneous or fasciocutaneous flaps were raised, mobilized, and designed according to the reconstructive needs as rotation, advancement, or turnover...... flaps. We performed 148 reconstructions in 130 patients. Eleven facial reconstructions, 118 reconstructions in the body, 7 in the upper limbs, and 12 in the lower limbs. The propeller flap was used in 135 of 148 (91%) cases followed by the turnover design in 10 (7%) and the V to Y flap in 3 (2%) cases...

  20. A steady-state target calculation method based on "point" model for integrating processes.

    Science.gov (United States)

    Pang, Qiang; Zou, Tao; Zhang, Yanyan; Cong, Qiumei

    2015-05-01

    Aiming to eliminate the influences of model uncertainty on the steady-state target calculation for integrating processes, this paper presented an optimization method based on "point" model and a method determining whether or not there is a feasible solution of steady-state target. The optimization method resolves the steady-state optimization problem of integrating processes under the framework of two-stage structure, which builds a simple "point" model for the steady-state prediction, and compensates the error between "point" model and real process in each sampling interval. Simulation results illustrate that the outputs of integrating variables can be restricted within the constraints, and the calculation errors between actual outputs and optimal set-points are small, which indicate that the steady-state prediction model can predict the future outputs of integrating variables accurately. Copyright © 2014 ISA. Published by Elsevier Ltd. All rights reserved.

  1. COSMID: A Web-based Tool for Identifying and Validating CRISPR/Cas Off-target Sites

    Directory of Open Access Journals (Sweden)

    Thomas J Cradick

    2014-01-01

    Full Text Available Precise genome editing using engineered nucleases can significantly facilitate biological studies and disease treatment. In particular, clustered regularly interspaced short palindromic repeats (CRISPR with CRISPR-associated (Cas proteins are a potentially powerful tool for modifying a genome by targeted cleavage of DNA sequences complementary to designed guide strand RNAs. Although CRISPR/Cas systems can have on-target cleavage rates close to the transfection rates, they may also have relatively high off-target cleavage at similar genomic sites that contain one or more base pair mismatches, and insertions or deletions relative to the guide strand. We have developed a bioinformatics-based tool, COSMID (CRISPR Off-target Sites with Mismatches, Insertions, and Deletions that searches genomes for potential off-target sites (http://crispr.bme.gatech.edu. Based on the user-supplied guide strand and input parameters, COSMID identifies potential off-target sites with the specified number of mismatched bases and insertions or deletions when compared with the guide strand. For each site, amplification primers optimal for the chosen application are also given as output. This ranked-list of potential off-target sites assists the choice and evaluation of intended target sites, thus helping the design of CRISPR/Cas systems with minimal off-target effects, as well as the identification and quantification of CRISPR/Cas induced off-target cleavage in cells.

  2. Lookup Tables-based mean level detection of spatially distributed targets in non Gaussian clutter

    Directory of Open Access Journals (Sweden)

    Nabila Nouar

    2017-08-01

    Full Text Available In this paper, Constant False Alarm Rate (CFAR detection of spatially distributed targets embedded in compound Gaussian clutter with Inverse Gamma texture is addressed. By taking into account the fact that clutter parameters are unknown in practical situations, we propose mean level based on Lookup Tables detectors, that operate as a two-step approach, which consists of computing threshold factors that maintain a Constant Probability of False Alarm (Pfa using intensive Monte Carlo simulations, and storing these factors in Lookup Tables, this first step is done independently from the detection algorithm. Then, at the detection stage, the detectors structure is associated to the Maximum Likelihood (ML estimation technique to estimate the shape and the scale parameters, and compare them to the closest integer and half integer values in the Lookup Tables, to select the suitable threshold factor. Under the High Resolution Radar (HRR assumption, the target is spread over a number of cells according to the Multiple Dominant scattering centers (MDS representation. The binary total binary hypothesis tests are derived using the expression of the overall target energy, which is computed as the sum of the energies reflected from each cell. Performance analysis of the proposed detectors is carried out using Monte Carlo simulation for various couples of clutter parameters and MDS models, and are compared to those of the Cell Averaging Based on Lookup Tables detector (CA-LT. In order to assess the performances of the proposed detectors in terms of the radar resolution, their performances are compared to the case of point-like targets.

  3. Automated mediastinal lymph node detection from CT volumes based on intensity targeted radial structure tensor analysis.

    Science.gov (United States)

    Oda, Hirohisa; Bhatia, Kanwal K; Oda, Masahiro; Kitasaka, Takayuki; Iwano, Shingo; Homma, Hirotoshi; Takabatake, Hirotsugu; Mori, Masaki; Natori, Hiroshi; Schnabel, Julia A; Mori, Kensaku

    2017-10-01

    This paper presents a local intensity structure analysis based on an intensity targeted radial structure tensor (ITRST) and the blob-like structure enhancement filter based on it (ITRST filter) for the mediastinal lymph node detection algorithm from chest computed tomography (CT) volumes. Although the filter based on radial structure tensor analysis (RST filter) based on conventional RST analysis can be utilized to detect lymph nodes, some lymph nodes adjacent to regions with extremely high or low intensities cannot be detected. Therefore, we propose the ITRST filter, which integrates the prior knowledge on detection target intensity range into the RST filter. Our lymph node detection algorithm consists of two steps: (1) obtaining candidate regions using the ITRST filter and (2) removing false positives (FPs) using the support vector machine classifier. We evaluated lymph node detection performance of the ITRST filter on 47 contrast-enhanced chest CT volumes and compared it with the RST and Hessian filters. The detection rate of the ITRST filter was 84.2% with 9.1 FPs/volume for lymph nodes whose short axis was at least 10 mm, which outperformed the RST and Hessian filters.

  4. Target berthing and base reorientation of free-floating space robotic system after capturing

    Science.gov (United States)

    Xu, Wenfu; Li, Cheng; Liang, Bin; Xu, Yangsheng; Liu, Yu; Qiang, Wenyi

    2009-01-01

    Space robots are playing an increasingly important role in on-orbital servicing, including repairing, refueling, or de-orbiting the satellite. The target must be captured and berthed before the servicing task starts. However, the attitude of the base may lean much and needs re-orientating after capturing. In this paper, a method is proposed to berth the target, and re-orientate the base at the same time, using manipulator motion only. Firstly, the system state is formed of the attitude quaternion and joint variables, and the joint paths are parameterized by sinusoidal functions. Then, the trajectory planning is transformed to an optimization problem. The cost function, defined according to the accuracy requirements of system variables, is the function of the parameters to be determined. Finally, we solve the parameters using the particle swarm optimization algorithm. Two typical cases of the spacecraft with a 6-DOF manipulator are dynamically simulated, one is that the variation of base attitude is limited; the other is that both the base attitude and the joint rates are constrained. The simulation results verify the presented method.

  5. Targeting Pulmonary Tuberculosis using Nanocarrier-based Dry Powder Inhalation: Current Status and Futuristic Need.

    Science.gov (United States)

    Patil, Tulshidas S; Deshpande, Ashwini S; Deshpande, Shirish; Shende, Pravin

    2018-03-21

    Tuberculosis (TB) is a disease caused by the pathogen Mycobacterium tuberculosis. Prolonged administration of high dose antibiotics using oral and injectable routes and their associated side effects, show limitations to successful treatment outcome of TB. Nanocarrier-based dry powder inhalers (DPIs) may provide a breakthrough as an alternative therapeutic approach because of their stable, non-invasive nature and ability to target the drug at the site of infection. The current review focuses on the roadmap of the respiratory system, drug deposition and targeting at the site of infection via pulmonary route. This review will provide readers an overview of the existing literature of nanocarrier-based DPIs of anti-TB drugs. Among different nanocarriers, results of most of the proliposomes and polymeric particles-based DPIs with respect to their characterization parameters like encapsulation efficiency, drug loading, storage stability and aerodynamic properties are not encouraging, whereas surface engineered, nanostructured lipid carriers (NLCs) i.e. ligand attached-NLCs-based dry powder inhalers (NLCs-DPI) show promising results. But still there is a need to investigate them for in-vitro, ex-vivo, in-vivo and toxicity studies to achieve a market approval.

  6. Building a multifunctional aptamer-based DNA nanoassembly for targeted cancer therapy.

    Science.gov (United States)

    Wu, Cuichen; Han, Da; Chen, Tao; Peng, Lu; Zhu, Guizhi; You, Mingxu; Qiu, Liping; Sefah, Kwame; Zhang, Xiaobing; Tan, Weihong

    2013-12-11

    The ability to self-assemble one-dimensional DNA building blocks into two- and three-dimensional nanostructures via DNA/RNA nanotechnology has led to broad applications in bioimaging, basic biological mechanism studies, disease diagnosis, and drug delivery. However, the cellular uptake of most nucleic acid nanostructures is dependent on passive delivery or the enhanced permeability and retention effect, which may not be suitable for certain types of cancers, especially for treatment in vivo. To meet this need, we have constructed a multifunctional aptamer-based DNA nanoassembly (AptNA) for targeted cancer therapy. In particular, we first designed various Y-shaped functional DNA domains through predesigned base pair hybridization, including targeting aptamers, intercalated anticancer drugs, and therapeutic antisense oligonucleotides. Then these functional DNA domains were linked to an X-shaped DNA core connector, termed a building unit, through the complementary sequences in the arms of functional domains and connector. Finally, hundreds (~100-200) of these basic building units with 5'-modification of acrydite groups were further photo-cross-linked into a multifunctional and programmable aptamer-based nanoassembly structure able to take advantage of facile modular design and assembly, high programmability, excellent biostability and biocompatibility, as well as selective recognition and transportation. With these properties, AptNAs were demonstrated to have specific cytotoxic effect against leukemia cells. Moreover, the incorporation of therapeutic antisense oligonucleotides resulted in the inhibition of P-gp expression (a drug efflux pump to increase excretion of anticancer drugs) as well as a decrease in drug resistance. Therefore, these multifunctional and programmable aptamer-based DNA nanoassemblies show promise as candidates for targeted drug delivery and cancer therapy.

  7. Design challenges in nanoparticle-based platforms: Implications for targeted drug delivery systems

    Science.gov (United States)

    Mullen, Douglas Gurnett

    Characterization and control of heterogeneous distributions of nanoparticle-ligand components are major design challenges for nanoparticle-based platforms. This dissertation begins with an examination of poly(amidoamine) (PAMAM) dendrimer-based targeted delivery platform. A folic acid targeted modular platform was developed to target human epithelial cancer cells. Although active targeting was observed in vitro, active targeting was not found in vivo using a mouse tumor model. A major flaw of this platform design was that it did not provide for characterization or control of the component distribution. Motivated by the problems experienced with the modular design, the actual composition of nanoparticle-ligand distributions were examined using a model dendrimer-ligand system. High Pressure Liquid Chromatography (HPLC) resolved the distribution of components in samples with mean ligand/dendrimer ratios ranging from 0.4 to 13. A peak fitting analysis enabled the quantification of the component distribution. Quantified distributions were found to be significantly more heterogeneous than commonly expected and standard analytical parameters, namely the mean ligand/nanoparticle ratio, failed to adequately represent the component heterogeneity. The distribution of components was also found to be sensitive to particle modifications that preceded the ligand conjugation. With the knowledge gained from this detailed distribution analysis, a new platform design was developed to provide a system with dramatically improved control over the number of components and with improved batch reproducibility. Using semi-preparative HPLC, individual dendrimer-ligand components were isolated. The isolated dendrimer with precise numbers of ligands were characterized by NMR and analytical HPLC. In total, nine different dendrimer-ligand components were obtained with degrees of purity ≥80%. This system has the potential to serve as a platform to which a precise number of functional molecules

  8. Multi-Frequency Target Detection Techniques for DVB-T Based Passive Radar Sensors

    Directory of Open Access Journals (Sweden)

    Tatiana Martelli

    2016-09-01

    Full Text Available This paper investigates the possibility to improve target detection capability in a DVB-T- based passive radar sensor by jointly exploiting multiple digital television channels broadcast by the same transmitter of opportunity. Based on the remarkable results obtained by such a multi-frequency approach using other signals of opportunity (i.e., FM radio broadcast transmissions, we propose appropriate modifications to the previously devised signal processing techniques for them to be effective in the newly considered scenarios. The resulting processing schemes are extensively applied against experimental DVB-T-based passive radar data pertaining to different surveillance applications. The obtained results clearly show the effectiveness of the proposed multi-frequency approaches and demonstrate their suitability for application in the considered scenarios.

  9. Comparison of different target material options for the European Spallation Source based on certain aspects related to the final disposal

    Science.gov (United States)

    Kókai, Zsófia; Török, Szabina; Zagyvai, Péter; Kiselev, Daniela; Moormann, Rainer; Börcsök, Endre; Zanini, Luca; Takibayev, Alan; Muhrer, Günter; Bevilacqua, Riccardo; Janik, József

    2018-02-01

    Different target options have been examined for the European Spallation Source, which is under construction in Lund, Sweden. During the design update phase, parameters and characteristics for the target design have been optimized not only for neutronics but also with respect to the waste characteristics related to the final disposal of the target. A rotating, solid tungsten target was eventually selected as baseline concept; the other options considered included mercury and lead-bismuth (LBE) targets suitable for a pulsed source. Since the licensee is obliged to present a decommissioning plan even before the construction phase starts, the radioactive waste category of the target after full operation time is of crucial importance. The results obtained from a small survey among project partners of 7th Framework Program granted by EU 202247 contract have been used. Waste characteristics of different potential spallation target materials were compared. Based on waste index, the tungsten target is the best alternative and the second one is the mercury target. However, all alternatives have HLW category after a 10 year cooling. Based on heat generation alone all of the options would be below the HLW limit after this cooling period. The LBE is the least advantageous alternative based on waste index and heat generation comparison. These results can be useful in compiling the licensing documents of the ESS facility as the target alternatives can be compared from various aspects related to their disposal.

  10. Interval MULTIMOORA method with target values of attributes based on interval distance and preference degree: biomaterials selection

    Science.gov (United States)

    Hafezalkotob, Arian; Hafezalkotob, Ashkan

    2017-12-01

    A target-based MADM method covers beneficial and non-beneficial attributes besides target values for some attributes. Such techniques are considered as the comprehensive forms of MADM approaches. Target-based MADM methods can also be used in traditional decision-making problems in which beneficial and non-beneficial attributes only exist. In many practical selection problems, some attributes have given target values. The values of decision matrix and target-based attributes can be provided as intervals in some of such problems. Some target-based decision-making methods have recently been developed; however, a research gap exists in the area of MADM techniques with target-based attributes under uncertainty of information. We extend the MULTIMOORA method for solving practical material selection problems in which material properties and their target values are given as interval numbers. We employ various concepts of interval computations to reduce degeneration of uncertain data. In this regard, we use interval arithmetic and introduce innovative formula for interval distance of interval numbers to create interval target-based normalization technique. Furthermore, we use a pairwise preference matrix based on the concept of degree of preference of interval numbers to calculate the maximum, minimum, and ranking of these numbers. Two decision-making problems regarding biomaterials selection of hip and knee prostheses are discussed. Preference degree-based ranking lists for subordinate parts of the extended MULTIMOORA method are generated by calculating the relative degrees of preference for the arranged assessment values of the biomaterials. The resultant rankings for the problem are compared with the outcomes of other target-based models in the literature.

  11. The insect ecdysone receptor is a good potential target for RNAi-based pest control.

    Science.gov (United States)

    Yu, Rong; Xu, Xinping; Liang, Yongkang; Tian, Honggang; Pan, Zhanqing; Jin, Shouheng; Wang, Na; Zhang, Wenqing

    2014-01-01

    RNA interference (RNAi) has great potential for use in insect pest control. However, some significant challenges must be overcome before RNAi-based pest control can become a reality. One challenge is the proper selection of a good target gene for RNAi. Here, we report that the insect ecdysone receptor (EcR) is a good potential target for RNAi-based pest control in the brown planthopper Nilaparvata lugens, a serious insect pest of rice plants. We demonstrated that the use of a 360 bp fragment (NlEcR-c) that is common between NlEcR-A and NlEcR-B for feeding RNAi experiments significantly decreased the relative mRNA expression levels of NlEcR compared with those in the dsGFP control. Feeding RNAi also resulted in a significant reduction in the number of offspring per pair of N. lugens. Consequently, a transgenic rice line expressing NlEcR dsRNA was constructed by Agrobacterium- mediated transformation. The results of qRT-PCR showed that the total copy number of the target gene in all transgenic rice lines was 2. Northern blot analysis showed that the small RNA of the hairpin dsNlEcR-c was successfully expressed in the transgenic rice lines. After newly hatched nymphs of N. lugens fed on the transgenic rice lines, effective RNAi was observed. The NlEcR expression levels in all lines examined were decreased significantly compared with the control. In all lines, the survival rate of the nymphs was nearly 90%, and the average number of offspring per pair in the treated groups was significantly less than that observed in the control, with a decrease of 44.18-66.27%. These findings support an RNAi-based pest control strategy and are also important for the management of rice insect pests.

  12. Wavelet-based estimator versus spectral correlation method for acoustic target sizing

    International Nuclear Information System (INIS)

    Scipioni, A; Rischette, P; Schweitzer, P; Mathieu, J

    2009-01-01

    This paper presents two different methods for estimating the diameter of an immersed wire insonified by an ultrasonic plane wave. The first part of the backscattered echo, called the quasi-rigid backscattered echo (QRBE), and the quasi-rigid form function (QRFF) are described first. It is shown that the QRBE contains the size information (diameter) of the target. In the first method, this size is obtained by associating a pattern recognition procedure with a spectral correlation. The second method is based on a continuous wavelet analysis of the QRBE at a particular scale with a judiciously selected wavelet. After a brief description of the wavelet tool, we present in detail the wavelet-based approach for target sizing. Results thus obtained are compared with experimental measurements using copper and steel wires. They show that for the largest diameters, the results are similar. On the other hand, the more the diameter decreases, the more the wavelet-based estimator is distinguished by giving a better relative precision. In terms of the cost of calculation, the second method is better since it requires only one wavelet transform at only one single scale against a Fourier transform and an iterative correlation procedure, necessary in the first technique

  13. SAR Target Recognition Based on Multi-feature Multiple Representation Classifier Fusion

    Directory of Open Access Journals (Sweden)

    Zhang Xinzheng

    2017-10-01

    Full Text Available In this paper, we present a Synthetic Aperture Radar (SAR image target recognition algorithm based on multi-feature multiple representation learning classifier fusion. First, it extracts three features from the SAR images, namely principal component analysis, wavelet transform, and Two-Dimensional Slice Zernike Moments (2DSZM features. Second, we harness the sparse representation classifier and the cooperative representation classifier with the above-mentioned features to get six predictive labels. Finally, we adopt classifier fusion to obtain the final recognition decision. We researched three different classifier fusion algorithms in our experiments, and the results demonstrate thatusing Bayesian decision fusion gives thebest recognition performance. The method based on multi-feature multiple representation learning classifier fusion integrates the discrimination of multi-features and combines the sparse and cooperative representation classification performance to gain complementary advantages and to improve recognition accuracy. The experiments are based on the Moving and Stationary Target Acquisition and Recognition (MSTAR database,and they demonstrate the effectiveness of the proposed approach.

  14. Human disease MiRNA inference by combining target information based on heterogeneous manifolds.

    Science.gov (United States)

    Ding, Pingjian; Luo, Jiawei; Liang, Cheng; Xiao, Qiu; Cao, Buwen

    2018-04-01

    The emergence of network medicine has provided great insight into the identification of disease-related molecules, which could help with the development of personalized medicine. However, the state-of-the-art methods could neither simultaneously consider target information and the known miRNA-disease associations nor effectively explore novel gene-disease associations as a by-product during the process of inferring disease-related miRNAs. Computational methods incorporating multiple sources of information offer more opportunities to infer disease-related molecules, including miRNAs and genes in heterogeneous networks at a system level. In this study, we developed a novel algorithm, named inference of Disease-related MiRNAs based on Heterogeneous Manifold (DMHM), to accurately and efficiently identify miRNA-disease associations by integrating multi-omics data. Graph-based regularization was utilized to obtain a smooth function on the data manifold, which constitutes the main principle of DMHM. The novelty of this framework lies in the relatedness between diseases and miRNAs, which are measured via heterogeneous manifolds on heterogeneous networks integrating target information. To demonstrate the effectiveness of DMHM, we conducted comprehensive experiments based on HMDD datasets and compared DMHM with six state-of-the-art methods. Experimental results indicated that DMHM significantly outperformed the other six methods under fivefold cross validation and de novo prediction tests. Case studies have further confirmed the practical usefulness of DMHM. Copyright © 2018 Elsevier Inc. All rights reserved.

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

    Directory of Open Access Journals (Sweden)

    Katja Spiess

    2017-01-01

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

  16. Diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19+tumors.

    Science.gov (United States)

    Zheng, Qian; Wang, Zhaohui; Zhang, Huiping; Huang, Qi; Madsen, Joren C; Sachs, David H; Huang, Christene A; Wang, Zhirui

    2017-05-01

    CD19 is expressed on normal and neoplastic B cells and is a promising target for immunotherapy. However, there is still an unmet need to further develop novel therapeutic drugs for the treatment of the refractory/relapsing human CD19 + tumors. We have developed a diphtheria toxin-based anti-human CD19 immunotoxin for targeting human CD19 + tumors. We have constructed three isoforms of the CD19 immunotoxin: monovalent, bivalent, and foldback diabody. In vitro binding affinity and efficacy analysis demonstrated that the bivalent isoform had the highest binding affinity and in vitro efficacy. The in vivo efficacy of the CD19 immunotoxins was assessed using human CD19 + JeKo-1 tumor-bearing NOD/SCID IL-2 receptor γ -/- (NSG) mouse model. In these animals, CD19 immunotoxins significantly prolonged the median survival from 31 days in controls to 34, 36, and 40 days in animals receiving the monovalent isoform, foldback diabody isoform, and bivalent isoform, respectively. The bivalent CD19 immunotoxin is a promising therapeutic drug candidate for targeting relapsing/refractory human CD19 + tumors. © 2017 The Authors. Published by FEBS Press and John Wiley & Sons Ltd.

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

    Directory of Open Access Journals (Sweden)

    Chao Zhang

    2017-07-01

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

  18. Analysis of the Chirplet Transform-Based Algorithm for Radar Detection of Accelerated Targets

    Science.gov (United States)

    Galushko, V. G.; Vavriv, D. M.

    2017-06-01

    Purpose: Efficiency analysis of an optimal algorithm of chirp signal processing based on the chirplet transform as applied to detection of radar targets in uniformly accelerated motion. Design/methodology/approach: Standard methods of the optimal filtration theory are used to investigate the ambiguity function of chirp signals. Findings: An analytical expression has been derived for the ambiguity function of chirp signals that is analyzed with respect to detection of radar targets moving at a constant acceleration. Sidelobe level and characteristic width of the ambiguity function with respect to the coordinates frequency and rate of its change have been estimated. The gain in the signal-to-noise ratio has been assessed that is provided by the algorithm under consideration as compared with application of the standard Fourier transform to detection of chirp signals against a “white” noise background. It is shown that already with a comparatively small (processing channels (elementary filters with respect to the frequency change rate) the gain in the signal-tonoise ratio exceeds 10 dB. A block diagram of implementation of the algorithm under consideration is suggested on the basis of a multichannel weighted Fourier transform. Recommendations as for selection of the detection algorithm parameters have been developed. Conclusions: The obtained results testify to efficiency of application of the algorithm under consideration to detection of radar targets moving at a constant acceleration. Nevertheless, it seems expedient to perform computer simulations of its operability with account for the noise impact along with trial measurements in real conditions.

  19. Designing calcium phosphate-based bifunctional nanocapsules with bone-targeting properties

    Energy Technology Data Exchange (ETDEWEB)

    Khung, Yit-Lung; Bastari, Kelsen; Cho, Xing Ling; Yee, Wu Aik; Loo, Say Chye Joachim, E-mail: joachimloo@ntu.edu.sg [Nanyang Technological University, School of Materials Science and Engineering (Singapore)

    2012-06-15

    Using sodium dodecyl sulphate micelles as template, hollow-cored calcium phosphate nanocapsules were produced. The surfaces of the nanocapsule were subsequently silanised by a polyethylene glycol (PEG)-based silane with an N-hydroxysuccinimide ester end groups which permits for further attachment with bisphosphonates (BP). Characterisations of these nanocapsules were investigated using Field Emission Scanning Electron Microscopy (FESEM), Transmission Electron Microscopy, Fourier Transform Infra-Red Spectroscopy, X-ray diffraction, X-ray photoelectron spectroscopy and Dynamic Light Scattering. To further validate the bone-targeting potential, dentine discs were incubated with these functionalised nanocapsules. FESEM analysis showed that these surface-modified nanocapsules would bind strongly to dentine surfaces compared to non-functionalised nanocapsules. We envisage that respective components would give this construct a bifunctional attribute, whereby (1) the shell of the calcium phosphate nanocapsule would serve as biocompatible coating aiding in gradual osteoconduction, while (2) surface BP moieties, acting as targeting ligands, would provide the bone-targeting potential of these calcium phosphate nanocapsules.

  20. Community based social marketing for implementation of energy saving targets at local level

    Directory of Open Access Journals (Sweden)

    Dalia Streimikiene

    2015-05-01

    Full Text Available Energy saving and greenhouse gas (GHG emission reduction policies at local level need to be investigated and new tools for climate change mitigation are necessary seeking to achieve GHG emission targets in Lithuania. Most Lithuanian municipalities have signed Covenant of Mayors and have prepared local energy action plans. However, all these plans include just energy saving measures on supply side and renovation of buildings. Nevertheless, the significant energy savings and GHG emission reductions can be achieved through behavioural changes. The aim of the paper is to apply community based social marketing approach in assessment of achievable energy saving and GHG emission reduction targets set by local energy action plans. The paper presents the results of case study implemented in Kaunas region municipality. The case study was conducted by creating focus groups and applying two scenarios: baseline or doing nothing and climate change mitigation scenario including intervention measures. The results of case study revealed that the total energy consumption reduction target set in Sustainable energy development strategy of Kaunas region county - 11% - can be achieved by combining results of energy consumption reduction in both focus groups. The survey conducted after study finalization revealed that respondents were provided with a lot of additional knowledge during the study and achieved real money savings. The major barriers of energy savings in households are related with the lack of information on energy savings and GHG emission reduction.

  1. Nucleic acid-based vaccines targeting respiratory syncytial virus: Delivering the goods.

    Science.gov (United States)

    Smith, Trevor R F; Schultheis, Katherine; Broderick, Kate E

    2017-11-02

    Respiratory syncytial virus (RSV) is a massive medical burden on a global scale. Infants, children and the elderly represent the vulnerable populations. Currently there is no approved vaccine to protect against the disease. Vaccine development has been hindered by several factors including vaccine enhanced disease (VED) associated with formalin-inactivated RSV vaccines, inability of target populations to raise protective immune responses after vaccination or natural viral infection, and a lack of consensus concerning the most appropriate virus-associated target antigen. However, with recent advances in the molecular understanding of the virus, and design of highly characterized vaccines with enhanced immunogenicity there is new belief a RSV vaccine is possible. One promising approach is nucleic acid-based vaccinology. Both DNA and mRNA RSV vaccines are showing promising results in clinically relevant animal models, supporting their transition into humans. Here we will discuss this strategy to target RSV, and the ongoing studies to advance the nucleic acid vaccine platform as a viable option to protect vulnerable populations from this important disease.

  2. Method for Multiple Targets Tracking in Cognitive Radar Based on Compressed Sensing

    Directory of Open Access Journals (Sweden)

    Yang Jun

    2016-02-01

    Full Text Available A multiple targets cognitive radar tracking method based on Compressed Sensing (CS is proposed. In this method, the theory of CS is introduced to the case of cognitive radar tracking process in multiple targets scenario. The echo signal is sparsely expressed. The designs of sparse matrix and measurement matrix are accomplished by expressing the echo signal sparsely, and subsequently, the restruction of measurement signal under the down-sampling condition is realized. On the receiving end, after considering that the problems that traditional particle filter suffers from degeneracy, and require a large number of particles, the particle swarm optimization particle filter is used to track the targets. On the transmitting end, the Posterior Cramér-Rao Bounds (PCRB of the tracking accuracy is deduced, and the radar waveform parameters are further cognitively designed using PCRB. Simulation results show that the proposed method can not only reduce the data quantity, but also provide a better tracking performance compared with traditional method.

  3. High-flux neutron source based on a liquid-lithium target

    Science.gov (United States)

    Halfon, S.; Feinberg, G.; Paul, M.; Arenshtam, A.; Berkovits, D.; Kijel, D.; Nagler, A.; Eliyahu, I.; Silverman, I.

    2013-04-01

    A prototype compact Liquid Lithium Target (LiLiT), able to constitute an accelerator-based intense neutron source, was built. The neutron source is intended for nuclear astrophysical research, boron neutron capture therapy (BNCT) in hospitals and material studies for fusion reactors. The LiLiT setup is presently being commissioned at Soreq Nuclear research Center (SNRC). The lithium target will produce neutrons through the 7Li(p,n)7Be reaction and it will overcome the major problem of removing the thermal power generated by a high-intensity proton beam, necessary for intense neutron flux for the above applications. The liquid-lithium loop of LiLiT is designed to generate a stable lithium jet at high velocity on a concave supporting wall with free surface toward the incident proton beam (up to 10 kW). During off-line tests, liquid lithium was flown through the loop and generated a stable jet at velocity higher than 5 m/s on the concave supporting wall. The target is now under extensive test program using a high-power electron-gun. Up to 2 kW electron beam was applied on the lithium flow at velocity of 4 m/s without any flow instabilities or excessive evaporation. High-intensity proton beam irradiation will take place at SARAF (Soreq Applied Research Accelerator Facility) superconducting linear accelerator currently in commissioning at SNRC.

  4. A fluorescent carbon-dots-based mitochondria-targetable nanoprobe for peroxynitrite sensing in living cells.

    Science.gov (United States)

    Wu, Xiaoxue; Sun, Shan; Wang, Yuhui; Zhu, Jiali; Jiang, Kai; Leng, Yumin; Shu, Qinghai; Lin, Hengwei

    2017-04-15

    Mitochondria, the power generators in cell, are a primary organelle of oxygen consumption and a main source of reactive oxygen/nitrogen species (ROS/RNS). Peroxynitrite (ONOO - ), known as a kind of RNS, has been considered to be a significant factor in many cell-related biological processes, and there is great desire to develop fluorescent probes that can sensitively and selectively detect peroxynitrite in living cells. Herein, we developed a fluorescent carbon-dots (C-dots) based mitochondria-targetable nanoprobe with high sensitivity and selectivity for peroxynitrite sensing in living cells. The C-dots with its surface rich in amino groups was synthesized using o-phenylenediamine as carbon precursor, and it could be covalently conjugated with a mitochondria-targeting moiety, i.e. triphenylphosphonium (TPP). In the presence of peroxynitrite, the fluorescence of the constructed nanoprobe (C-dots-TPP) was efficiently quenched via a mechanism of photoinduced electron transfer (PET). The nanoprobe exhibited relatively high sensitivity (limit of detection: 13.5nM) and selectivity towards peroxynitrite in aqueous buffer. The performance of the nanoprobe for fluorescence imaging of peroxynitrite in mitochondria was investigated. The results demonstrated that the nanoprobe showed fine mitochondria-targeting ability and imaging contrast towards peroxynitrite in living cells. We anticipate that the proposed nanoprobe will provide a facile tool to explore the role played by peroxynitrite in cytobiology. Copyright © 2016 Elsevier B.V. All rights reserved.

  5. Biologically based vision simulation for target-background discrimination and camouflage/LO design

    Science.gov (United States)

    Doll, Theodore J.; McWhorter, Shane W.; Schmieder, David E.; Hetzler, Morris C.; Stewart, John M.; Wasilewski, Anthony A.; Owens, William R.; Sheffer, Albert D., Jr.; Galloway, Gregory L.; Harbert, Simeon D.

    1997-06-01

    The Georgia Tech Research Institute has developed an integrated suite of software for Visual and Electro-Optical (VISEO) detection analysis, under the sponsorship of the Army Aviation and Troop Command, Aviation Applied Technology Directorate. The VISEO system is a comprehensive workstation-based tool for multi-spectral signature analysis, LO design, and visualization of targets moving through real measured backgrounds. A key component of the VISEO system is a simulation of real measured backgrounds. A key component of the VISEO system is a simulation of human vision, called the Georgia Tech Vision (GTV) simulation. The algorithms used in the simulation are consistent with neurophysiological evidence concerning the functions of the human visual system, from dynamic light adaptation processes in the retinal receptors and ganglia to the processing of motion, color, and edge information in the striate cortex. The simulation accepts images seen by the naked eye or through direct-view optical systems, as well as images viewed on the displays of IR sensors, image intensifiers and night-vision devices. GTV outputs predicted probabilities that the target is fixated (Pfix) during visual search, and detected (Pd), and also identifies specific features of the target that contribute most to successful search and detection performance. This paper outlines the capabilities and structure of the VISEO system, emphasizing GTV. Example results of visible and IR signature reduction on the basis of VISEO will be shown and described.

  6. FPGA-Based Real-Time Moving Target Detection System for Unmanned Aerial Vehicle Application

    Directory of Open Access Journals (Sweden)

    Jia Wei Tang

    2016-01-01

    Full Text Available Moving target detection is the most common task for Unmanned Aerial Vehicle (UAV to find and track object of interest from a bird’s eye view in mobile aerial surveillance for civilian applications such as search and rescue operation. The complex detection algorithm can be implemented in a real-time embedded system using Field Programmable Gate Array (FPGA. This paper presents the development of real-time moving target detection System-on-Chip (SoC using FPGA for deployment on a UAV. The detection algorithm utilizes area-based image registration technique which includes motion estimation and object segmentation processes. The moving target detection system has been prototyped on a low-cost Terasic DE2-115 board mounted with TRDB-D5M camera. The system consists of Nios II processor and stream-oriented dedicated hardware accelerators running at 100 MHz clock rate, achieving 30-frame per second processing speed for 640 × 480 pixels’ resolution greyscale videos.

  7. Suppression of Repeat-Intensive False Targets Based on Temporal Pulse Diversity

    Directory of Open Access Journals (Sweden)

    Gang Lu

    2013-01-01

    Full Text Available This paper considers the problem of suppressing the repeat-intensive false targets produced by a deception electronic attack (EA system equipped with a Digital Radio Frequency Memory (DRFM device. Different from a conventional repeat jammer, this type of jamming intensively retransmits the intercepted signal stored in a DRFM to the victim radar in a very short time-delay interval relative to a radar pulse wide. A multipeak matched-filtering output is then produced other than the merely expected true target. An electronic protection (EP algorithm based on the space time block code (STBC is proposed to suppress the adverse effects of this jammer. By transmitting a pulse sequence generated from the STBC in succession and the following cancellation process applied upon the received signal, this algorithm performs successfully in a single antenna system provided that the target models are nonfluctuating or slow fluctuating and the pulse repetition frequency (PRF is comparatively high. The performance in white and correlated Gaussian disturbance is evaluated by means of Monte Carlo simulations.

  8. NPACT: Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database.

    Science.gov (United States)

    Mangal, Manu; Sagar, Parul; Singh, Harinder; Raghava, Gajendra P S; Agarwal, Subhash M

    2013-01-01

    Plant-derived molecules have been highly valued by biomedical researchers and pharmaceutical companies for developing drugs, as they are thought to be optimized during evolution. Therefore, we have collected and compiled a central resource Naturally Occurring Plant-based Anti-cancer Compound-Activity-Target database (NPACT, http://crdd.osdd.net/raghava/npact/) that gathers the information related to experimentally validated plant-derived natural compounds exhibiting anti-cancerous activity (in vitro and in vivo), to complement the other databases. It currently contains 1574 compound entries, and each record provides information on their structure, manually curated published data on in vitro and in vivo experiments along with reference for users referral, inhibitory values (IC(50)/ED(50)/EC(50)/GI(50)), properties (physical, elemental and topological), cancer types, cell lines, protein targets, commercial suppliers and drug likeness of compounds. NPACT can easily be browsed or queried using various options, and an online similarity tool has also been made available. Further, to facilitate retrieval of existing data, each record is hyperlinked to similar databases like SuperNatural, Herbal Ingredients' Targets, Comparative Toxicogenomics Database, PubChem and NCI-60 GI(50) data.

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

    Science.gov (United States)

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

    2017-05-06

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

  10. Predicting the Types of Ion Channel-Targeted Conotoxins Based on AVC-SVM Model.

    Science.gov (United States)

    Xianfang, Wang; Junmei, Wang; Xiaolei, Wang; Yue, Zhang

    2017-01-01

    The conotoxin proteins are disulfide-rich small peptides. Predicting the types of ion channel-targeted conotoxins has great value in the treatment of chronic diseases, epilepsy, and cardiovascular diseases. To solve the problem of information redundancy existing when using current methods, a new model is presented to predict the types of ion channel-targeted conotoxins based on AVC (Analysis of Variance and Correlation) and SVM (Support Vector Machine). First, the F value is used to measure the significance level of the feature for the result, and the attribute with smaller F value is filtered by rough selection. Secondly, redundancy degree is calculated by Pearson Correlation Coefficient. And the threshold is set to filter attributes with weak independence to get the result of the refinement. Finally, SVM is used to predict the types of ion channel-targeted conotoxins. The experimental results show the proposed AVC-SVM model reaches an overall accuracy of 91.98%, an average accuracy of 92.17%, and the total number of parameters of 68. The proposed model provides highly useful information for further experimental research. The prediction model will be accessed free of charge at our web server.

  11. Identification of Specific Inhibitors of Trypanosoma cruzi Malic Enzyme Isoforms by Target-Based HTS.

    Science.gov (United States)

    Ranzani, Americo T; Nowicki, Cristina; Wilkinson, Shane R; Cordeiro, Artur T

    2017-04-01

    Trypanosoma cruzi is the causative agent of Chagas disease. The lack of an efficient and safe treatment supports the research into novel metabolic targets, with the malic enzyme (ME) representing one such potential candidate. T. cruzi expresses a cytosolic (TcMEc) and a mitochondrial (TcMEm) ME isoform, with these activities functioning to generate NADPH, a key source of reducing equivalents that drives a range of anabolic and protective processes. To identify specific inhibitors that target TcMEs, two independent high-throughput screening strategies using a diversity library containing 30,000 compounds were employed. IC 50 values of 262 molecules were determined for both TcMEs, as well as for three human ME isoforms, with the inhibitors clustered into six groups according to their chemical similarity. The most potent hits belonged to a sulfonamide group that specifically target TcMEc. Moreover, several selected inhibitors of both TcMEs showed a trypanocidal effect against the replicative forms of T. cruzi. The chemical diversity observed among those compounds that inhibit TcMEs activity emphasizes the druggability of these enzymes, with a sulfonamide-based subset of compounds readily able to block TcMEc function at a low nanomolar range.

  12. Lipid-Based Nanovectors for Targeting of CD44-Overexpressing Tumor Cells

    Directory of Open Access Journals (Sweden)

    Silvia Arpicco

    2013-01-01

    Full Text Available Hyaluronic acid (HA is a naturally occurring glycosaminoglycan that exists in living systems, and it is a major component of the extracellular matrix. The hyaluronic acid receptor CD44 is found at low levels on the surface of epithelial, haematopoietic, and neuronal cells and is overexpressed in many cancer cells particularly in tumour initiating cells. HA has been therefore used as ligand attached to HA-lipid-based nanovectors for the active targeting of small or large active molecules for the treatment of cancer. This paper describes the different approaches employed for the preparation, characterization, and evaluation of these potent delivery systems.

  13. Targeted High Performance Liquid Chromatography Tandem Mass Spectrometry-based Metabolomics differentiates metabolic syndrome from obesity.

    Science.gov (United States)

    Zhong, Fanyi; Xu, Mengyang; Bruno, Richard S; Ballard, Kevin D; Zhu, Jiangjiang

    2017-04-01

    Both obesity and the metabolic syndrome are risk factors for type 2 diabetes and cardiovascular disease. Identification of novel biomarkers are needed to distinguish metabolic syndrome from equally obese individuals in order to direct them to early interventions that reduce their risk of developing further health problems. We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to evaluate the associations between metabolite profiles and established metabolic syndrome criteria (i.e. elevated waist circumference, hypertension, elevated fasting glucose, elevated triglycerides, and low high-density lipoprotein cholesterol) in plasma samples from obese men ( n = 29; BMI = 35.5 ± 5.2 kg/m 2 ) and women ( n = 40; 34.9 ± 6.7 kg/m 2 ), of which 26 met the criteria for metabolic syndrome (17 men and 9 women). Compared to obese individuals without metabolic syndrome, univariate statistical analysis and partial least squares discriminant analysis showed that a specific group of metabolites from multiple metabolic pathways (i.e. purine metabolism, valine, leucine and isoleucine degradation, and tryptophan metabolism) were associated with the presence of metabolic syndrome. Receiver operating characteristic curves generated based on the PLS-DA models showed excellent areas under the curve (0.85 and 0.96, for metabolites only model and enhanced metabolites model, respectively), high specificities (0.86 and 0.93), and good sensitivities (0.71 and 0.91). Moreover, principal component analysis revealed that metabolic profiles can be used to further differentiate metabolic syndrome with 3 versus 4-5 metabolic syndrome criteria. Collectively, these findings support targeted metabolomics approaches to distinguish metabolic syndrome from obesity alone, and to stratify metabolic syndrome status based on the number of criteria met. Impact statement We utilized mass spectrometry-based targeted metabolic profiling of 221 metabolites to

  14. Optical implementation of a feature-based neural network with application to automatic target recognition

    Science.gov (United States)

    Chao, Tien-Hsin; Stoner, William W.

    1993-01-01

    An optical neural network based on the neocognitron paradigm is introduced. A novel aspect of the architecture design is shift-invariant multichannel Fourier optical correlation within each processing layer. Multilayer processing is achieved by feeding back the ouput of the feature correlator interatively to the input spatial light modulator and by updating the Fourier filters. By training the neural net with characteristic features extracted from the target images, successful pattern recognition with intraclass fault tolerance and interclass discrimination is achieved. A detailed system description is provided. Experimental demonstrations of a two-layer neural network for space-object discrimination is also presented.

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

    Science.gov (United States)

    Chao, Tien-Hsin

    1992-01-01

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

  16. Common Risk Target for severe accidents of nuclear power plants based on IAEA INES scale

    International Nuclear Information System (INIS)

    Vitázková, Jiřina; Cazzoli, Errico

    2013-01-01

    The IAEA has repeatedly recommended that the nuclear community should arrive at a common understanding and definition of safety goals for severe accidents in nuclear power plants. The recommendation has only found partial answers, despite the numerous working groups and forums devoted to this effort. The most widely accepted definition of goals is based on the concept of Large (Early) Release Frequencies (L(E)RF) and its derivatives, a surrogate concept derived from results of Probabilistic Safety Assessments (PSAs) which was first introduced in the USA almost twenty years ago and much later accepted by the USNRC for risk informed decision making, but not for safety demonstrations. Other types of Safety Goals have been adopted by some nuclear authorities, but the main drawback of all current definitions is that they may apply only to LWRs. The lack of unifying safety/risk parameter throughout of PSAs worldwide is the basis of the present work, and an attempt is made to arrive at the definition of a Risk Target for severe accidents in NPPs, consistent with the IAEA definitions having a technical basis, which can be adopted without modifications for Generation IV power plants. The proposal of Common Risk Target in this work represents an attempt to define a Common Risk Target based on technical reasoning, reflecting IAEA definitions as well as harmonization requirements raised by the whole European Community in various OECD, ASAMPSA2 and SARNET (Guentay et al., 2006) conclusions and Council Directive of The European Union (Community Framework, 2009) as well as lastly performed stress tests of nuclear power plants throughout the Europe (Peer Review Report, 2012). The basic concept of CRT was first introduced and developed within the European project ASAMPSA2 by the authors of this article and was accepted by majority of world PSA experts participating in final evaluation and survey of the project (Guentay, 2011). In the proposed Risk Target concept an innovative

  17. Outcome based definition of the anterior thalamic deep brain stimulation target in refractory epilepsy.

    Science.gov (United States)

    Lehtimäki, K; Möttönen, T; Järventausta, K; Katisko, J; Tähtinen, T; Haapasalo, J; Niskakangas, T; Kiekara, T; Öhman, J; Peltola, J

    2016-01-01

    Deep brain stimulation of the anterior nucleus of the thalamus (ANT) is an emerging therapy for refractory focal epilepsy. However, the most optimal target for stimulation has not been unambiguously described. In the present study, we investigated the correlation between the stimulation site and outcome in order to define the optimal target for deep brain stimulation in refractory epilepsy. The locations of 62 contacts used in 30 treatment attempts in 15 prospectively followed patients during a 5 year period were assessed. Treatment attempts were classified into responding and non-responding trials using seizure reduction and side effect profile as criteria. The locations of active contacts were calculated with respect to mid-commissural point and visible borders of ANT in 3T MRI (ANT-normalized coordinate system) aiming to minimize the confounding effect of individual variation in the location and size of the ANT. Contacts in successful treatment trials were located significantly more anterior and superior both in AC-PC and ANT-normalized coordinate systems. Favourable outcome was observed at 3T MRI based location of ANT but not at location predicted by Schaltenbrandt atlas sagittal data. Contacts used in successful trials were at anterior aspect of the ANT complex evidenced by the ANT-normalized coordinate system. The anti-epileptic effect of anterior thalamic DBS may be dependent on stimulation site especially in the anterior to posterior axis. Extensive anatomical variation confounds severely the targeting of ANT. Therefore, direct visualization of the desired target for stimulation is essential for favourable outcome in refractory epilepsy. Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

  18. The polypharmacology browser: a web-based multi-fingerprint target prediction tool using ChEMBL bioactivity data.

    Science.gov (United States)

    Awale, Mahendra; Reymond, Jean-Louis

    2017-01-01

    Several web-based tools have been reported recently which predict the possible targets of a small molecule by similarity to compounds of known bioactivity using molecular fingerprints (fps), however predictions in each case rely on similarities computed from only one or two fps. Considering that structural similarity and therefore the predicted targets strongly depend on the method used for comparison, it would be highly desirable to predict targets using a broader set of fps simultaneously. Herein, we present the polypharmacology browser (PPB), a web-based platform which predicts possible targets for small molecules by searching for nearest neighbors using ten different fps describing composition, substructures, molecular shape and pharmacophores. PPB searches through 4613 groups of at least 10 same target annotated bioactive molecules from ChEMBL and returns a list of predicted targets ranked by consensus voting scheme and p value. A validation study across 670 drugs with up to 20 targets showed that combining the predictions from all 10 fps gives the best results, with on average 50% of the known targets of a drug being correctly predicted with a hit rate of 25%. Furthermore, when profiling a new inhibitor of the calcium channel TRPV6 against 24 targets taken from a safety screen panel, we observed inhibition in 5 out of 5 targets predicted by PPB and in 7 out of 18 targets not predicted by PPB. The rate of correct (5/12) and incorrect (0/12) predictions for this compound by PPB was comparable to that of other web-based prediction tools. PPB offers a versatile platform for target prediction based on multi-fingerprint comparisons, and is freely accessible at www.gdb.unibe.ch as a valuable support for drug discovery.Graphical abstract.

  19. Development of a PVD-based manufacturing process of monolithic LEU irradiation targets for {sup 99}Mo production

    Energy Technology Data Exchange (ETDEWEB)

    Hollmer, Tobias

    2015-08-03

    {sup 99}Mo is the most important radioisotope in nuclear medicine. It is produced by fission of uranium in irradiation targets. The usage of cylindrical monolithic targets can ensure a safe supply of {sup 99}Mo and at the same reduce the amount of highly radioactive waste generated during production. To manufacture these targets, a novel PVD-based technique was developed. Both the feasibility and the high efficiency of this process were demonstrated in a prototype apparatus.

  20. Stem Cell-Based Cell Carrier for Targeted Oncolytic Virotherapy: Translational Opportunity and Open Questions

    Directory of Open Access Journals (Sweden)

    Janice Kim

    2015-11-01

    Full Text Available Oncolytic virotherapy for cancer is an innovative therapeutic option where the ability of a virus to promote cell lysis is harnessed and reprogrammed to selectively destroy cancer cells. Such treatment modalities exhibited antitumor activity in preclinical and clinical settings and appear to be well tolerated when tested in clinical trials. However, the clinical success of oncolytic virotherapy has been significantly hampered due to the inability to target systematic metastasis. This is partly due to the inability of the therapeutic virus to survive in the patient circulation, in order to target tumors at distant sites. An early study from various laboratories demonstrated that cells infected with oncolytic virus can protect the therapeutic payload form the host immune system as well as function as factories for virus production and enhance the therapeutic efficacy of oncolytic virus. While a variety of cell lineages possessed potential as cell carriers, copious investigation has established stem cells as a very attractive cell carrier system in oncolytic virotherapy. The ideal cell carrier desire to be susceptible to viral infection as well as support viral infection, maintain immunosuppressive properties to shield the loaded viruses from the host immune system, and most importantly possess an intrinsic tumor homing ability to deliver loaded viruses directly to the site of the metastasis—all qualities stem cells exhibit. In this review, we summarize the recent work in the development of stem cell-based carrier for oncolytic virotherapy, discuss the advantages and disadvantages of a variety of cell carriers, especially focusing on why stem cells have emerged as the leading candidate, and finally propose a future direction for stem cell-based targeted oncolytic virotherapy that involves its establishment as a viable treatment option for cancer patients in the clinical setting.

  1. Chalcone-based small-molecule inhibitors attenuate malignant phenotype via targeting deubiquitinating enzymes

    Science.gov (United States)

    Issaenko, Olga A.; Amerik, Alexander Yu

    2012-01-01

    The ubiquitin-proteasome system (UPS) is usurped by many if not all cancers to regulate their survival, proliferation, invasion, angiogenesis and metastasis. Bioflavonoids curcumin and chalcones exhibit anti-neoplastic selectivity through inhibition of the 26S proteasome-activity within the UPS. Here, we provide evidence for a novel mechanism of action of chalcone-based derivatives AM146, RA-9 and RA-14, which exert anticancer activity by targeting deubiquitinating enzymes (DUB) without affecting 20S proteasome catalytic-core activity. The presence of the α,β-unsaturated carbonyl group susceptible to nucleophilic attack from the sulfhydryl of cysteines in the active sites of DUB determines the capacity of novel small-molecules to act as cell-permeable, partly selective DUB inhibitors and induce rapid accumulation of polyubiquitinated proteins and deplete the pool of free ubiquitin. These chalcone-derivatives directly suppress activity of DUB UCH-L1, UCH-L3, USP2, USP5 and USP8, which are known to regulate the turnover and stability of key regulators of cell survival and proliferation. Inhibition of DUB-activity mediated by these compounds downregulates cell-cycle promoters, e.g., cyclin D1 and upregulates tumor suppressors p53, p27Kip1 and p16Ink4A. These changes are associated with arrest in S-G2/M, abrogated anchorage-dependent growth and onset of apoptosis in breast, ovarian and cervical cancer cells without noticeable alterations in primary human cells. Altogether, this work provides evidence of antitumor activity of novel chalcone-based derivatives mediated by their DUB-targeting capacity; supports the development of pharmaceuticals to directly target DUB as a most efficient strategy compared with proteasome inhibition and also provides a clear rationale for the clinical evaluation of these novel small-molecule DUB inhibitors. PMID:22510564

  2. Biomass-based targets and the management of multispecies coral reef fisheries.

    Science.gov (United States)

    McClanahan, T R; Graham, N A J; MacNeil, M A; Cinner, J E

    2015-04-01

    The failure of fisheries management among multispecies coral reef fisheries is well documented and has dire implications for the 100 million people engaged in these small-scale operations. Weak or missing management institutions, a lack of research capacity, and the complex nature of these ecosystems have heralded a call for ecosystem-based management approaches. However, ecosystem-based management of coral reef fisheries has proved challenging due to the multispecies nature of catches and the diversity of fish functional roles. We used data on fish communities collected from 233 individual sites in 9 western Indian Ocean countries to evaluate changes in the site's functional composition and associated life-history characteristics along a large range of fish biomass. As biomass increased along this range, fish were larger and grew and matured more slowly while the abundance of scraping and predatory species increased. The greatest changes in functional composition occurred below relatively low standing stock biomass (<600 kg/ha); abundances of piscivores, apex predators, and scraping herbivores were low at very light levels of fishing. This suggests potential trade-offs in ecosystem function and estimated yields for different management systems. Current fishing gear and area restrictions are not achieving conservation targets (proposed here as standing stock biomass of 1150 kg/ha) and result in losses of life history and ecological functions. Fish in reefs where destructive gears were restricted typically had very similar biomass and functions to young and low compliance closures. This indicates the potentially important role of fisheries restrictions in providing some gains in biomass and associated ecological functions when fully protected area enforcement potential is limited and likely to fail. Our results indicate that biomass alone can provide broad ecosystem-based fisheries management targets that can be easily applied even where research capacity and

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

    Directory of Open Access Journals (Sweden)

    Alexander D M Wilson

    Full Text Available Recently, there has been growing recognition that fish harvesting practices can have important impacts on the phenotypic distributions and diversity of natural populations through a phenomenon known as fisheries-induced evolution. Here we experimentally show that two common recreational angling techniques (active crank baits versus passive soft plastics differentially target wild largemouth bass (Micropterus salmoides and rock bass (Ambloplites rupestris based on variation in their behavioural tendencies. Fish were first angled in the wild using both techniques and then brought back to the laboratory and tested for individual-level differences in common estimates of personality (refuge emergence, flight-initiation-distance, latency-to-recapture and with a net, and general activity in an in-lake experimental arena. We found that different angling techniques appear to selectively target these species based on their boldness (as characterized by refuge emergence, a standard measure of boldness in fishes but not other assays of personality. We also observed that body size was independently a significant predictor of personality in both species, though this varied between traits and species. Our results suggest a context-dependency for vulnerability to capture relative to behaviour in these fish species. Ascertaining the selective pressures angling practices exert on natural populations is an important area of fisheries research with significant implications for ecology, evolution, and resource management.

  4. Adaptive Energy-Efficient Target Detection Based on Mobile Wireless Sensor Networks

    Directory of Open Access Journals (Sweden)

    Tengyue Zou

    2017-05-01

    Full Text Available Target detection is a widely used application for area surveillance, elder care, and fire alarms; its purpose is to find a particular object or event in a region of interest. Usually, fixed observing stations or static sensor nodes are arranged uniformly in the field. However, each part of the field has a different probability of being intruded upon; if an object suddenly enters an area with few guardian devices, a loss of detection will occur, and the stations in the safe areas will waste their energy for a long time without any discovery. Thus, mobile wireless sensor networks may benefit from adaptation and pertinence in detection. Sensor nodes equipped with wheels are able to move towards the risk area via an adaptive learning procedure based on Bayesian networks. Furthermore, a clustering algorithm based on k-means++ and an energy control mechanism is used to reduce the energy consumption of nodes. The extended Kalman filter and a voting data fusion method are employed to raise the localization accuracy of the target. The simulation and experimental results indicate that this new system with adaptive energy-efficient methods is able to achieve better performance than the traditional ones.

  5. A flexible calibration method for laser displacement sensors based on a stereo-target

    International Nuclear Information System (INIS)

    Zhang, Jie; Sun, Junhua; Liu, Zhen; Zhang, Guangjun

    2014-01-01

    Laser displacement sensors (LDSs) are widely used in online measurement owing to their characteristics of non-contact, high measurement speed, etc. However, existing calibration methods for LDSs based on the traditional triangulation measurement model are time-consuming and tedious to operate. In this paper, a calibration method for LDSs based on a vision measurement model of the LDS is presented. According to the constraint relationships of the model parameters, the calibration is implemented by freely moving a stereo-target at least twice in the field of view of the LDS. Both simulation analyses and real experiments were conducted. Experimental results demonstrate that the calibration method achieves an accuracy of 0.044 mm within the measurement range of about 150 mm. Compared to traditional calibration methods, the proposed method has no special limitation on the relative position of the LDS and the target. The linearity approximation of the measurement model in the calibration is not needed, and thus the measurement range is not limited in the linearity range. It is easy and quick to implement the calibration for the LDS. The method can be applied in wider fields. (paper)

  6. Targeted Tumor Therapy Based on Nanodiamonds Decorated with Doxorubicin and Folic Acid.

    Science.gov (United States)

    Ryu, Tae-Kyung; Baek, Seung Woon; Lee, Gyoung-Ja; Rhee, Chang-Kyu; Choi, Sung-Wook

    2017-02-01

    The fabrication of nanodiamond (ND)-based drug carriers for tumor-targeted drug delivery is described. The ND clusters with an average size of 52.84 nm are fabricated using a simple fluidic device combined with a precipitation method and then conjugated with folic acid (FA) and doxorubicin (Dox) via carbodiimide chemistry to obtain FA/Dox-modified ND (FA/Dox-ND) clusters. Cell culture experiments revealed that KB (folate receptor-positive) cells are preferentially ablated by FA/Dox-ND clusters compared to A549 (folate receptor-negative) cells. In vivo results revealed that FA/Dox-ND clusters are specifically accumulated in tumor tissues after intravenous injection into tumor-bearing mice, effectively reducing the volume of tumor. Based on these results, this study suggests that FA/Dox-ND clusters can be a good candidate as tumor-targeted nanovehicles for delivery of antitumor drug. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

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

    Science.gov (United States)

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

    2015-01-01

    Recently, there has been growing recognition that fish harvesting practices can have important impacts on the phenotypic distributions and diversity of natural populations through a phenomenon known as fisheries-induced evolution. Here we experimentally show that two common recreational angling techniques (active crank baits versus passive soft plastics) differentially target wild largemouth bass (Micropterus salmoides) and rock bass (Ambloplites rupestris) based on variation in their behavioural tendencies. Fish were first angled in the wild using both techniques and then brought back to the laboratory and tested for individual-level differences in common estimates of personality (refuge emergence, flight-initiation-distance, latency-to-recapture and with a net, and general activity) in an in-lake experimental arena. We found that different angling techniques appear to selectively target these species based on their boldness (as characterized by refuge emergence, a standard measure of boldness in fishes) but not other assays of personality. We also observed that body size was independently a significant predictor of personality in both species, though this varied between traits and species. Our results suggest a context-dependency for vulnerability to capture relative to behaviour in these fish species. Ascertaining the selective pressures angling practices exert on natural populations is an important area of fisheries research with significant implications for ecology, evolution, and resource management.

  8. Adaptive Energy-Efficient Target Detection Based on Mobile Wireless Sensor Networks.

    Science.gov (United States)

    Zou, Tengyue; Li, Zhenjia; Li, Shuyuan; Lin, Shouying

    2017-05-04

    Target detection is a widely used application for area surveillance, elder care, and fire alarms; its purpose is to find a particular object or event in a region of interest. Usually, fixed observing stations or static sensor nodes are arranged uniformly in the field. However, each part of the field has a different probability of being intruded upon; if an object suddenly enters an area with few guardian devices, a loss of detection will occur, and the stations in the safe areas will waste their energy for a long time without any discovery. Thus, mobile wireless sensor networks may benefit from adaptation and pertinence in detection. Sensor nodes equipped with wheels are able to move towards the risk area via an adaptive learning procedure based on Bayesian networks. Furthermore, a clustering algorithm based on k -means++ and an energy control mechanism is used to reduce the energy consumption of nodes. The extended Kalman filter and a voting data fusion method are employed to raise the localization accuracy of the target. The simulation and experimental results indicate that this new system with adaptive energy-efficient methods is able to achieve better performance than the traditional ones.

  9. An estimation of distribution method for infrared target detection based on Copulas

    Science.gov (United States)

    Wang, Shuo; Zhang, Yiqun

    2015-10-01

    Track-before-detect (TBD) based target detection involves a hypothesis test of merit functions which measure each track as a possible target track. Its accuracy depends on the precision of the distribution of merit functions, which determines the threshold for a test. Generally, merit functions are regarded Gaussian, and on this basis the distribution is estimated, which is true for most methods such as the multiple hypothesis tracking (MHT). However, merit functions for some other methods such as the dynamic programming algorithm (DPA) are non-Guassian and cross-correlated. Since existing methods cannot reasonably measure the correlation, the exact distribution can hardly be estimated. If merit functions are assumed Guassian and independent, the error between an actual distribution and its approximation may occasionally over 30 percent, and is divergent by propagation. Hence, in this paper, we propose a novel estimation of distribution method based on Copulas, by which the distribution can be estimated precisely, where the error is less than 1 percent without propagation. Moreover, the estimation merely depends on the form of merit functions and the structure of a tracking algorithm, and is invariant to measurements. Thus, the distribution can be estimated in advance, greatly reducing the demand for real-time calculation of distribution functions.

  10. Modified Anderson-Darling Test-Based Target Detector in Non-Homogenous Environments

    Directory of Open Access Journals (Sweden)

    Yang Li

    2014-08-01

    Full Text Available A constant false alarm rate (CFAR target detector in non-homogenous backgrounds is proposed. Based on K-sample Anderson-Darling (AD tests, the method re-arranges the reference cells by merging homogenous sub-blocks surrounding the cell under test (CUT into a new reference window to estimate the background statistics. Double partition test, clutter edge refinement and outlier elimination are used as an anti-clutter processor in the proposed Modified AD (MAD detector. Simulation results show that the proposed MAD test based detector outperforms cell-averaging (CA CFAR, greatest of (GO CFAR, smallest of (SO CFAR, order-statistic (OS CFAR, variability index (VI CFAR, and CUT inclusive (CI CFAR in most non-homogenous situations.

  11. Modified Anderson-Darling test-based target detector in non-homogenous environments.

    Science.gov (United States)

    Li, Yang; Wei, Yinsheng; Li, Bingfei; Alterovitz, Gil

    2014-08-29

    A constant false alarm rate (CFAR) target detector in non-homogenous backgrounds is proposed. Based on K-sample Anderson-Darling (AD) tests, the method re-arranges the reference cells by merging homogenous sub-blocks surrounding the cell under test (CUT) into a new reference window to estimate the background statistics. Double partition test, clutter edge refinement and outlier elimination are used as an anti-clutter processor in the proposed Modified AD (MAD) detector. Simulation results show that the proposed MAD test based detector outperforms cell-averaging (CA) CFAR, greatest of (GO) CFAR, smallest of (SO) CFAR, order-statistic (OS) CFAR, variability index (VI) CFAR, and CUT inclusive (CI) CFAR in most non-homogenous situations.

  12. Locality Preserving Projection Based on Endmember Extraction for Hyperspectral Image Dimensionality Reduction and Target Detection.

    Science.gov (United States)

    Wang, Yiting; Huang, Shiqi; Liu, Zhigang; Wang, Hongxia; Liu, Daizhi

    2016-09-01

    In order to reduce the effect of spectral variability on calculation precision for the weighted matrix in the locality preserving projection (LPP) algorithm, an improved dimensionality reduction method named endmember extraction-based locality preserving projection (EE-LPP) is proposed in this paper. The method primarily uses the vertex component analysis (VCA) method to extract endmember spectra from hyperspectral imagery. It then calculates the similarity between pixel spectra and the endmember spectra by using the spectral angle distance, and uses it as the basis for selecting neighboring pixels in the image and constructs a weighted matrix between pixels. Finally, based on the weighted matrix, the idea of the LPP algorithm is applied to reduce the dimensions of hyperspectral image data. Experimental results of real hyperspectral data demonstrate that the low-dimensional features acquired by the proposed methods can fully reflect the characteristics of the original image and further improve target detection accuracy. © The Author(s) 2016.

  13. Quantifying Synergy, Thermostability, and Targeting of Cellulolytic Enzymes and Cellulosomes with Polymerization-Based Amplification.

    Science.gov (United States)

    Malinowska, Klara H; Rind, Thomas; Verdorfer, Tobias; Gaub, Hermann E; Nash, Michael A

    2015-07-21

    We present a polymerization-based assay for determining the potency of cellulolytic enzyme formulations on pretreated biomass substrates. Our system relies on monitoring the autofluorescence of cellulose and measuring the attenuation of this fluorescent signal as a hydrogel consisting of poly(ethylene glycol) (PEG) polymerizes on top of the cellulose in response to glucose produced during saccharification. The one-pot method we present is label-free, rapid, highly sensitive, and requires only a single pipetting step. Using model enzyme formulations derived from Trichoderma reesei, Trichoderma longibrachiatum, Talaromyces emersonii and recombinant bacterial minicellulosomes from Clostridium thermocellum, we demonstrate the ability to differentiate enzyme performance based on differences in thermostability, cellulose-binding domain targeting, and endo/exoglucanase synergy. On the basis of its ease of use, we expect this cellulase assay platform to be applicable to enzyme screening for improved bioconversion of lignocellulosic biomass.

  14. Recent Trends in Nanotechnology-Based Drugs and Formulations for Targeted Therapeutic Delivery.

    Science.gov (United States)

    Iqbal, Hafiz M N; Rodriguez, Angel M V; Khandia, Rekha; Munjal, Ashok; Dhama, Kuldeep

    2017-01-01

    In the recent past, a wider spectrum of nanotechnologybased drugs or drug-loaded devices and systems has been engineered and investigated with high interests. The key objective is to help for an enhanced/better quality of patient life in a secure way by avoiding/limiting drug abuse, or severe adverse effects of some in practice traditional therapies. Various methodological approaches including in vitro, in vivo, and ex vivo techniques have been exploited, so far. Among them, nanoparticles-based therapeutic agents are of supreme interests for an enhanced and efficient delivery in the current biomedical sector of the modern world. The development of new types of novel, effective and highly reliable therapeutic drug delivery system (DDS) for multipurpose applications is essential and a core demand to tackle many human health related diseases. In this context, nanotechnology-based several advanced DDS have been engineered with novel characteristics for biomedical, pharmaceutical and cosmeceutical applications that include but not limited to the enhanced/improved bioactivity, bioavailability, drug efficacy, targeted delivery, and therapeutically safer with an extra advantage of overcoming demerits of traditional drug formulations/designs. This review work is focused on recent trends/advances in nanotechnology-based drugs and formulations designed for targeted therapeutic delivery. Moreover, information is also reviewed and given from recent patents and summarized or illustrated diagrammatically to depict a better understanding. Recent patents covering various nanotechnology-based approaches for several applications have also been reviewed. The drug-loaded nanoparticles are among versatile candidates with multifunctional characteristics for potential applications in biomedical, and tissue engineering sector. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  15. Relationship among reaction rate, release rate and efficiency of nanomachine-based targeted drug delivery.

    Science.gov (United States)

    Zhao, Qingying; Li, Min; Luo, Jun

    2017-12-04

    In nanomachine applications towards targeted drug delivery, drug molecules released by nanomachines propagate and chemically react with tumor cells in aqueous environment. If the nanomachines release drug molecules faster than the tumor cells react, it will result in loss and waste of drug molecules. It is a potential issue associated with the relationship among reaction rate, release rate and efficiency. This paper aims to investigate the relationship among reaction rate, release rate and efficiency based on two drug reception models. We expect to pave a way for designing a control method of drug release. We adopted two analytical methods that one is drug reception process based on collision with tumors and another is based on Michaelis Menten enzymatic kinetics. To evaluate the analytical formulations, we used the well-known simulation framework N3Sim to establish simulations. The analytical results of the relationship among reaction rate, release rate and efficiency is obtained, which match well with the numerical simulation results in a 3-D environment. Based upon two drug reception models, the results of this paper would be beneficial for designing a control method of nanomahine-based drug release.

  16. A Plane Target Detection Algorithm in Remote Sensing Images based on Deep Learning Network Technology

    Science.gov (United States)

    Shuxin, Li; Zhilong, Zhang; Biao, Li

    2018-01-01

    Plane is an important target category in remote sensing targets and it is of great value to detect the plane targets automatically. As remote imaging technology developing continuously, the resolution of the remote sensing image has been very high and we can get more detailed information for detecting the remote sensing targets automatically. Deep learning network technology is the most advanced technology in image target detection and recognition, which provided great performance improvement in the field of target detection and recognition in the everyday scenes. We combined the technology with the application in the remote sensing target detection and proposed an algorithm with end to end deep network, which can learn from the remote sensing images to detect the targets in the new images automatically and robustly. Our experiments shows that the algorithm can capture the feature information of the plane target and has better performance in target detection with the old methods.

  17. Frame-Based Immobilization and Targeting for Stereotactic Body Radiation Therapy

    International Nuclear Information System (INIS)

    Murray, Bryan C.; Forster, Kenneth; Timmerman, Robert

    2007-01-01

    Frame-based stereotactic body radiation therapy (SBRT), such as that conducted with Elekta's Stereotactic Body Frame, can provide an extra measure of precision in the delivery of radiation to extracranial targets, and facilitates secure patient immobilization. In this paper, we review the steps involved in optimal use of an extra-cranial immobilization device for SBRT treatments. Our approach to using frame-based SBRT consists of 4 steps: patient immobilization, tumor and organ motion control, treatment/planning correlation, and daily targeting with pretreatment quality assurance. Patient immobilization was achieved with the Vac-Loc bag, which uses styrofoam beads to conform to the patient's shape comfortably within the body frame. Organ and motion control was assessed under fluoroscopy and controlled via a frame-mounted abdominal pressure plate. The compression screw was tightened until the diaphragmatic excursion range was < 1 cm. Treatment planning was performed using the Philips Pinnacle 6.2b system. In this treatment process, a 20 to 30 noncoplanar beam arrangement was initially selected and an inverse beam weight optimization algorithm was applied. Those beams with low beam weights were removed, leaving a manageable number of beams for treatment delivery. After planning, daily targeting using computed tomography (CT) to verify x-, y-, and z-coordinates of the treatment isocenter were used as a measure of quality assurance. We found our daily setup variation typically averaged < 5 mm in all directions, which is comparable to other published studies on Stereotactic Body Frame. Treatment time ranged from 30 to 45 minutes. Results demonstrate that patients have experienced high rates of local control with acceptable rates of severe side effects-by virtue of the tightly constrained treatment fields. The body frame facilitated comfortable patient positioning and quality assurance checks of the tumor, in relation to another set of independent set of coordinates

  18. Laser Guidestar Satellite for Ground-based Adaptive Optics Imaging of Geosynchronous Satellites and Astronomical Targets

    Science.gov (United States)

    Marlow, W. A.; Cahoy, K.; Males, J.; Carlton, A.; Yoon, H.

    2015-12-01

    Real-time observation and monitoring of geostationary (GEO) satellites with ground-based imaging systems would be an attractive alternative to fielding high cost, long lead, space-based imagers, but ground-based observations are inherently limited by atmospheric turbulence. Adaptive optics (AO) systems are used to help ground telescopes achieve diffraction-limited seeing. AO systems have historically relied on the use of bright natural guide stars or laser guide stars projected on a layer of the upper atmosphere by ground laser systems. There are several challenges with this approach such as the sidereal motion of GEO objects relative to natural guide stars and limitations of ground-based laser guide stars; they cannot be used to correct tip-tilt, they are not point sources, and have finite angular sizes when detected at the receiver. There is a difference between the wavefront error measured using the guide star compared with the target due to cone effect, which also makes it difficult to use a distributed aperture system with a larger baseline to improve resolution. Inspired by previous concepts proposed by A.H. Greenaway, we present using a space-based laser guide starprojected from a satellite orbiting the Earth. We show that a nanosatellite-based guide star system meets the needs for imaging GEO objects using a low power laser even from 36,000 km altitude. Satellite guide star (SGS) systemswould be well above atmospheric turbulence and could provide a small angular size reference source. CubeSatsoffer inexpensive, frequent access to space at a fraction of the cost of traditional systems, and are now being deployed to geostationary orbits and on interplanetary trajectories. The fundamental CubeSat bus unit of 10 cm cubed can be combined in multiple units and offers a common form factor allowing for easy integration as secondary payloads on traditional launches and rapid testing of new technologies on-orbit. We describe a 6U CubeSat SGS measuring 10 cm x 20 cm x

  19. A three-dimensional CT-based target definition for elective irradiation of the neck

    International Nuclear Information System (INIS)

    Nowak, Peter J.C.M.; Wijers, Oda B.; Lagerwaard, Frank J.; Levendag, Peter C.

    1999-01-01

    Introduction: Elective treatment of the clinically node-negative neck by radiation results in excellent control rates. However, radiation therapy with its organ-preserving properties is not without morbidity. Side effects of elective neck irradiation are mainly due to damage of the major and minor salivary glands, resulting in the dry mouth syndrome. Given that RT is the preferred treatment modality in case of elective treatment of the neck in many institutions, it is of utmost importance to try and reduce the associated sequelae of RT. Material and Methods: With the introduction of CT-planning systems and the development of 3D conformal radiation therapy (3D CRT) techniques, it has become feasible to deliver adequate doses of radiation to the target (neck) and at the same time saving (parts of) the salivary glands from doses beyond tolerance. A prerequisite for these techniques is that they require a precise knowledge of the target (i.e., of the elective neck) on CT. To be able to correlate borders of the surgical levels in the neck (I-VI) with structures seen on CT, an anatomical study, using two fixed (phenol, formaldehyde) human cadavers, was performed. Subsequently, the 6 potential lymph node regions in the neck on CT were defined. Results and Discussion: The reference for the current 3D CT-based definition of the lymph node regions in the neck is the official report of the American Academy of Otolaryngology, describing, based on surgical anatomy, the lymph node groups in the neck by Levels I-VI. The present investigation depicts reproducible landmarks on transversal CT images, corresponding to anatomical reference structures known from surgical levels (I-VI) and, this way, CT-based lymph node regions (1-6) were constructed

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

    Science.gov (United States)

    Ramasamy, Thilagavathi; Selvam, Chelliah

    2015-10-15

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

  1. Determining the Best Strategies for Maternally Targeted Pertussis Vaccination Using an Individual-Based Model.

    Science.gov (United States)

    Campbell, Patricia Therese; McVernon, Jodie; Geard, Nicholas

    2017-07-01

    Rising pertussis incidence has prompted a number of countries to implement maternally targeted vaccination strategies to protect vulnerable infants, but questions remain about the optimal design of such strategies. We simulated pertussis transmission within an individual-based model parameterized to match Australian conditions, explicitly linking infants and their mothers to estimate the effectiveness of alternative maternally targeted vaccination strategies (antenatal delivery vs. postnatal delivery) and the benefit of revaccination over the course of multiple pregnancies. For firstborn infants aged less than 2 months, antenatal immunization reduced annual pertussis incidence by 60%, from 780 per 100,000 firstborn children under age 2 months (interquartile range (IQR), 682-862) to 315 per 100,000 (IQR, 260-370), while postnatal vaccination produced a minimal reduction, with an incidence of 728 per 100,000 (IQR, 628-789). Subsequent infants obtained limited protection from a single antenatal dose, but revaccinating mothers during every pregnancy decreased incidence for these infants by 58%, from 1,878 per 100,000 subsequent children under age 2 months (IQR, 1,712-2,076) to 791 per 100,000 (IQR, 683-915). Subsequent infants also benefited from household-level herd immunity when antenatal vaccination for every pregnancy was combined with a toddler booster dose at age 18 months; incidence was reduced to 626 per 100,000 (IQR, 548-691). Our approach provides useful information to aid consideration of alternative maternally targeted vaccination strategies and can inform development of outcome measures for program evaluation. © The Author 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  2. Targeted Chemo-Photodynamic Combination Platform Based on the DOX Prodrug Nanoparticles for Enhanced Cancer Therapy.

    Science.gov (United States)

    Zhang, Yumin; Huang, Fan; Ren, Chunhua; Yang, Lijun; Liu, Jianfeng; Cheng, Zhen; Chu, Liping; Liu, Jinjian

    2017-04-19

    Chemo-photodynamic combination therapy has been received widespread attention in cancer treatment due to its excellent characteristics, such as reducing the adverse side effects of chemo-drugs and improving the therapeutic effects for various cancers. In this study, RGD and DOX was conjugated to PEG by thiol-ene addition and Schiff's base reaction, respectively, to prepare the targeted and pH-sensitive antitumor prodrug nanoparticles (RGD-PEG-DOX NPs, RGD-NPs). Subsequently, the photosensitizer chlorin e6 (Ce6) was encapsulated into RGD-NPs, thus obtaining a simple and efficient chemo-photodynamic combination platform (RGD-PEG-DOX/Ce6 NPs, RGD-NPs/Ce6). This nanoparticle possessed high drug loading property of both the chemo-drug and photosensitizer and could simultaneously release them under the mild acidic microenvironment of cancer cells, which was expected to realize the synchronization therapy of chemotherapy and photodynamic therapy (PDT). Compared with free DOX and Ce6, RGD-NPs/Ce6 could significantly improve the cellular uptake capacities of DOX and Ce6, resulting in the increased contents of ROS in cancer cells and effective cytotoxicity for tumor cells (MDA-MB-231 cells and MCF-7 cells) upon a laser radiation. The in vivo experiment showed that RGD-NPs/Ce6 displayed superior tumor targeting, accumulation, and retention ability than the other groups (free DOX, free Ce6 and NPs/Ce6), and thus significantly enhancing the antitumor effect in vivo with a laser radiation. In addition, the cardiotoxicity induced by DOX was thoroughly wiped out after being loaded and delivered by the nanoparticles according to the pathological analysis. Therefore, the targeted chemo-photodynamic combination therapeutic platform may be a promising candidate for enhanced cancer therapy.

  3. Structure-Based Modification of a Clostridium difficile-Targeting Endolysin Affects Activity and Host Range▿

    Science.gov (United States)

    Mayer, Melinda J.; Garefalaki, Vasiliki; Spoerl, Rebecca; Narbad, Arjan; Meijers, Rob

    2011-01-01

    Endolysin CD27L causes cell lysis of the pathogen Clostridium difficile, a major cause of nosocomial infection. We report a structural and functional analysis of the catalytic activity of CD27L against C. difficile and other bacterial strains. We show that truncation of the endolysin to the N-terminal domain, CD27L1–179, gave an increased lytic activity against cells of C. difficile, while the C-terminal region, CD27L180–270, failed to produce lysis. CD27L1–179 also has increased activity against other bacterial species that are targeted by the full-length protein and in addition was able to lyse some CD27L-insensitive strains. However, CD27L1–179 retained a measure of specificity, failing to lyse a wide range of bacteria. The use of green fluorescent protein (GFP)-labeled proteins demonstrated that both CD27L and CD27L1–179 bound to C. difficile cell walls. The crystal structure of CD27L1–179 confirms that the enzyme is a zinc-dependent N-acetylmuramoyl-l-alanine amidase. A structure-based sequence analysis allowed us to identify four catalytic residues, a proton relay cascade, and a substrate binding pocket. A BLAST search shows that the closest-related amidases almost exclusively target Clostridia. This implied that the catalytic domain alone contained features that target a specific bacterial species. To test this hypothesis, we modified Leu 98 to a Trp residue which is found in an endolysin from a bacteriophage of Listeria monocytogenes (PlyPSA). This mutation in CD27L resulted in an increased activity against selected serotypes of L. monocytogenes, demonstrating the potential to tune the species specificity of the catalytic domain of an endolysin. PMID:21803993

  4. Structure-based modification of a Clostridium difficile-targeting endolysin affects activity and host range.

    Science.gov (United States)

    Mayer, Melinda J; Garefalaki, Vasiliki; Spoerl, Rebecca; Narbad, Arjan; Meijers, Rob

    2011-10-01

    Endolysin CD27L causes cell lysis of the pathogen Clostridium difficile, a major cause of nosocomial infection. We report a structural and functional analysis of the catalytic activity of CD27L against C. difficile and other bacterial strains. We show that truncation of the endolysin to the N-terminal domain, CD27L1-179, gave an increased lytic activity against cells of C. difficile, while the C-terminal region, CD27L180-270, failed to produce lysis. CD27L1-179 also has increased activity against other bacterial species that are targeted by the full-length protein and in addition was able to lyse some CD27L-insensitive strains. However, CD27L1-179 retained a measure of specificity, failing to lyse a wide range of bacteria. The use of green fluorescent protein (GFP)-labeled proteins demonstrated that both CD27L and CD27L1-179 bound to C. difficile cell walls. The crystal structure of CD27L1-179 confirms that the enzyme is a zinc-dependent N-acetylmuramoyl-l-alanine amidase. A structure-based sequence analysis allowed us to identify four catalytic residues, a proton relay cascade, and a substrate binding pocket. A BLAST search shows that the closest-related amidases almost exclusively target Clostridia. This implied that the catalytic domain alone contained features that target a specific bacterial species. To test this hypothesis, we modified Leu 98 to a Trp residue which is found in an endolysin from a bacteriophage of Listeria monocytogenes (PlyPSA). This mutation in CD27L resulted in an increased activity against selected serotypes of L. monocytogenes, demonstrating the potential to tune the species specificity of the catalytic domain of an endolysin.

  5. Application of the Hard and Soft, Acids and Bases (HSAB) theory to toxicant--target interactions.

    Science.gov (United States)

    Lopachin, Richard M; Gavin, Terrence; Decaprio, Anthony; Barber, David S

    2012-02-20

    Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are, however, discriminatory since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acids and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic

  6. APPLICATION OF THE HARD AND SOFT, ACIDS AND BASES (HSAB) THEORY TO TOXICANT-TARGET INTERACTIONS

    Science.gov (United States)

    LoPachin, Richard M.; Gavin, Terrence; DeCaprio, Anthony; Barber, David S.

    2011-01-01

    Many chemical toxicants and/or their active metabolites are electrophiles that cause cell injury by forming covalent bonds with nucleophilic targets on biological macromolecules. Covalent reactions between nucleophilic and electrophilic reagents are however discriminatory, since there is a significant degree of selectivity associated with these interactions. Over the course of the past few decades, the theory of Hard and Soft, Acid and Bases (HSAB) has proven to be a useful tool in predicting the outcome of such reactions. This concept utilizes the inherent electronic characteristic of polarizability to define, for example, reacting electrophiles and nucleophiles as either hard or soft. These HSAB definitions have been successfully applied to chemical-induced toxicity in biological systems. Thus, according to this principle, a toxic electrophile reacts preferentially with biological targets of similar hardness or softness. The soft/hard classification of a xenobiotic electrophile has obvious utility in discerning plausible biological targets and molecular mechanisms of toxicity. The purpose of this Perspective is to discuss the HSAB theory of electrophiles and nucleophiles within a toxicological framework. In principle, covalent bond formation can be described by using the properties of their outermost or frontier orbitals. Because these orbital energies for most chemicals can be calculated using quantum mechanical models, it is possible to quantify the relative softness (σ) or hardness (η) of electrophiles or nucleophiles and to subsequently convert this information into useful indices of reactivity. This atomic level information can provide insight into the design of corroborative laboratory research and thereby help investigators discern corresponding molecular sites and mechanisms of toxicant action. The use of HSAB parameters has also been instrumental in the development and identification of potential nucleophilic cytoprotectants that can scavenge toxic

  7. EM-Based High Speed Wireless Sensor Networks for Underwater Surveillance and Target Tracking

    Directory of Open Access Journals (Sweden)

    Kumudu Munasinghe

    2017-01-01

    Full Text Available Underwater Wireless Sensor Networks (UWSNs are considered as tangible, low cost solution for underwater surveillance and exploration. Existing acoustic wave-based UWSN systems fail to meet the growing demand for fast data rates required in military operations, oil/gas exploration, and oceanographic data collection. Electromagnetic (EM wave-based communication systems, on the other hand, have great potential for providing high speed data rates in such scenarios. This paper will (1 discuss the challenges faced in the utilization of EM waves for the design of tactical underwater surveillance systems and (2 evaluate several EM wave-based three-dimensional (3D UWSN architectures differing in topologies and/or operation principles on the performance of localization and target tracking. To the best of our knowledge, this is the first of its kind in the field of underwater communications where underwater surveillance techniques for EM wave-based high speed UWSNs have been investigated. Thus, this will be a major step towards achieving future high speed UWSNs.

  8. Target tracking algorithm based on Kalman filter and optimization MeanShift

    Science.gov (United States)

    Wu, Heng; Han, Tao; Zhang, Jie

    2017-11-01

    Background change ,shape change and target covering will all cause target tracking failure. Real-time and accuracy in target tracking is the problem that must be considered. This paper first presents the Mean Shift algorithm, then the Mean Shift algorithm iterative weight is modified with main information more prominent, secondary information suppressed, avoiding the tedious root, improving the real-time and effectiveness of target tracking. The target template updating algorithm is present to solve change of background and target shape change. Then a Kalman filter in the horizontal position and the vertical position is established to solve the problem of target tracking completely covered. Simulation results show that target tracking algorithm on the condition of target template update has higher tracking accuracy , higher real-time property and at the same time is robust than the traditional Mean Shift tracking algorithm .

  9. Chimeric L2-Based Virus-Like Particle (VLP Vaccines Targeting Cutaneous Human Papillomaviruses (HPV.

    Directory of Open Access Journals (Sweden)

    Bettina Huber

    Full Text Available Common cutaneous human papillomavirus (HPV types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas, but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa 17-36 on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross- protected against beta HPV5/20/24/38/96/16 (but not type 76, while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target

  10. Chimeric L2-Based Virus-Like Particle (VLP) Vaccines Targeting Cutaneous Human Papillomaviruses (HPV).

    Science.gov (United States)

    Huber, Bettina; Schellenbacher, Christina; Shafti-Keramat, Saeed; Jindra, Christoph; Christensen, Neil; Kirnbauer, Reinhard

    2017-01-01

    Common cutaneous human papillomavirus (HPV) types induce skin warts, whereas species beta HPV are implicated, together with UV-radiation, in the development of non-melanoma skin cancer (NMSC) in immunosuppressed patients. Licensed HPV vaccines contain virus-like particles (VLP) self-assembled from L1 major capsid proteins that provide type-restricted protection against mucosal HPV infections causing cervical and other ano-genital and oro-pharyngeal carcinomas and warts (condylomas), but do not target heterologous HPV. Experimental papillomavirus vaccines have been designed based on L2 minor capsid proteins that contain type-common neutralization epitopes, to broaden protection to heterologous mucosal and cutaneous HPV types. Repetitive display of the HPV16 L2 cross-neutralization epitope RG1 (amino acids (aa) 17-36) on the surface of HPV16 L1 VLP has greatly enhanced immunogenicity of the L2 peptide. To more directly target cutaneous HPV, L1 fusion proteins were designed that incorporate the RG1 homolog of beta HPV17, the beta HPV5 L2 peptide aa53-72, or the common cutaneous HPV4 RG1 homolog, inserted into DE surface loops of HPV1, 5, 16 or 18 L1 VLP scaffolds. Baculovirus expressed chimeric proteins self-assembled into VLP and VLP-raised NZW rabbit immune sera were evaluated by ELISA and L1- and L2-based pseudovirion (PsV) neutralizing assays, including 12 novel beta PsV types. Chimeric VLP displaying the HPV17 RG1 epitope, but not the HPV5L2 aa53-72 epitope, induced cross-neutralizing humoral immune responses to beta HPV. In vivo cross-protection was evaluated by passive serum transfer in a murine PsV challenge model. Immune sera to HPV16L1-17RG1 VLP (cross-) protected against beta HPV5/20/24/38/96/16 (but not type 76), while antisera to HPV5L1-17RG1 VLP cross-protected against HPV20/24/96 only, and sera to HPV1L1-4RG1 VLP cross-protected against HPV4 challenge. In conclusion, RG1-based VLP are promising next generation vaccine candidates to target cutaneous HPV

  11. Essential proteins and possible therapeutic targets of Wolbachia endosymbiont and development of FiloBase--a comprehensive drug target database for Lymphatic filariasis.

    Science.gov (United States)

    Sharma, Om Prakash; Kumar, Muthuvel Suresh

    2016-01-25

    Lymphatic filariasis (Lf) is one of the oldest and most debilitating tropical diseases. Millions of people are suffering from this prevalent disease. It is estimated to infect over 120 million people in at least 80 nations of the world through the tropical and subtropical regions. More than one billion people are in danger of getting affected with this life-threatening disease. Several studies were suggested its emerging limitations and resistance towards the available drugs and therapeutic targets for Lf. Therefore, better medicine and drug targets are in demand. We took an initiative to identify the essential proteins of Wolbachia endosymbiont of Brugia malayi, which are indispensable for their survival and non-homologous to human host proteins. In this current study, we have used proteome subtractive approach to screen the possible therapeutic targets for wBm. In addition, numerous literatures were mined in the hunt for potential drug targets, drugs, epitopes, crystal structures, and expressed sequence tag (EST) sequences for filarial causing nematodes. Data obtained from our study were presented in a user friendly database named FiloBase. We hope that information stored in this database may be used for further research and drug development process against filariasis. URL: http://filobase.bicpu.edu.in.

  12. VIDA: a voxel-based dosimetry method for targeted radionuclide therapy using Geant4.

    Science.gov (United States)

    Kost, Susan D; Dewaraja, Yuni K; Abramson, Richard G; Stabin, Michael G

    2015-02-01

    We have developed the Voxel-Based Internal Dosimetry Application (VIDA) to provide patient-specific dosimetry in targeted radionuclide therapy performing Monte Carlo simulations of radiation transport with the Geant4 toolkit. The code generates voxel-level dose rate maps using anatomical and physiological data taken from individual patients. Voxel level dose rate curves are then fit and integrated to yield a spatial map of radiation absorbed dose. In this article, we present validation studies using established dosimetry results, including self-dose factors (DFs) from the OLINDA/EXM program for uniform activity in unit density spheres and organ self- and cross-organ DFs in the Radiation Dose Assessment Resource (RADAR) reference adult phantom. The comparison with reference data demonstrated agreement within 5% for self-DFs to spheres and reference phantom source organs for four common radionuclides used in targeted therapy ((131)I, (90)Y, (111)In, (177)Lu). Agreement within 9% was achieved for cross-organ DFs. We also present dose estimates to normal tissues and tumors from studies of two non-Hodgkin Lymphoma patients treated by (131)I radioimmunotherapy, with comparison to results generated independently with another dosimetry code. A relative difference of 12% or less was found between methods for mean absorbed tumor doses accounting for tumor regression.

  13. Oligonucleotide-based microarray analysis of retinoic acid target genes in the protochordate, Ciona intestinalis.

    Science.gov (United States)

    Ishibashi, Tomoko; Usami, Takeshi; Fujie, Manabu; Azumi, Kaoru; Satoh, Nori; Fujiwara, Shigeki

    2005-08-01

    Oligonucleotide-based microarray analyses were carried out to identify retinoic acid target genes in embryos of the ascidian Ciona intestinalis. Of 21,938 spots, 50 (corresponding to 43 genes) showed over twofold up-regulation in retinoic acid-treated tail bud embryos. In situ hybridization verified retinoic acid-induced up-regulation of 23 genes. Many of them were expressed in the anterior tail region, where a retinaldehyde dehydrogenase homolog is expressed. Homologs of vertebrate genes involved in neurogenesis and/or neuronal functions (e.g., COUP-TF, Ci-Hox1, and SCO-spondin) were expressed in the central nervous system of Ciona embryos, and activated by retinoic acid. Genes encoding transcription factors (e.g., Ci-lmx1.2, vitamin D receptor, and Hox proteins) and apoptosis-related proteins (e.g., transglutaminase and an apoptosis-inducing factor homolog) were also activated by retinoic acid. Simultaneous treatment of embryos with retinoic acid and puromycin revealed a few direct targets, including genes encoding Ci-Hox1, Ci-Cyp26, and an Rnf126-like ring finger protein. (c) 2005 Wiley-Liss, Inc.

  14. SVMRFE based approach for prediction of most discriminatory gene target for type II diabetes

    Directory of Open Access Journals (Sweden)

    Atul Kumar

    2017-06-01

    Full Text Available Type II diabetes is a chronic condition that affects the way our body metabolizes sugar. The body's important source of fuel is now becoming a chronic disease all over the world. It is now very necessary to identify the new potential targets for the drugs which not only control the disease but also can treat it. Support vector machines are the classifier which has a potential to make a classification of the discriminatory genes and non-discriminatory genes. SVMRFE a modification of SVM ranks the genes based on their discriminatory power and eliminate the genes which are not involved in causing the disease. A gene regulatory network has been formed with the top ranked coding genes to identify their role in causing diabetes. To further validate the results pathway study was performed to identify the involvement of the coding genes in type II diabetes. The genes obtained from this study showed a significant involvement in causing the disease, which may be used as a potential drug target.

  15. Can Hawaii Meet Its Renewable Fuel Target? Case Study of Banagrass-Based Cellulosic Ethanol

    Directory of Open Access Journals (Sweden)

    Chinh Tran

    2016-08-01

    Full Text Available Banagrass is a biomass crop candidate for ethanol production in the State of Hawaii. This study examines: (i whether enough banagrass can be produced to meet Hawaii’s renewable fuel target of 20% highway fuel demand produced with renewable sources by 2020 and (ii at what cost. This study proposes to locate suitable land areas for banagrass production and ethanol processing, focusing on the two largest islands in the state of Hawaii—Hawaii and Maui. The results suggest that the 20% target is not achievable by using all suitable land resources for banagrass production on both Hawaii and Maui. A total of about 74,224,160 gallons, accounting for 16.04% of the state’s highway fuel demand, can be potentially produced at a cost of $6.28/gallon. Lower ethanol cost is found when using a smaller production scale. The lowest cost of $3.31/gallon is found at a production processing capacity of about 9 million gallons per year (MGY, which meets about 2% of state demand. This cost is still higher than the average imported ethanol price of $3/gallon. Sensitivity analysis finds that it is possible to produce banagrass-based ethanol on Hawaii Island at a cost below the average imported ethanol price if banagrass yield increases of at least 35.56%.

  16. High-power liquid-lithium target prototype for accelerator-based boron neutron capture therapy.

    Science.gov (United States)

    Halfon, S; Paul, M; Arenshtam, A; Berkovits, D; Bisyakoev, M; Eliyahu, I; Feinberg, G; Hazenshprung, N; Kijel, D; Nagler, A; Silverman, I

    2011-12-01

    A prototype of a compact Liquid-Lithium Target (LiLiT), which will possibly constitute an accelerator-based intense neutron source for Boron Neutron Capture Therapy (BNCT) in hospitals, was built. The LiLiT setup is presently being commissioned at Soreq Nuclear Research Center (SNRC). The liquid-lithium target will produce neutrons through the (7)Li(p,n)(7)Be reaction and it will overcome the major problem of removing the thermal power generated using a high-intensity proton beam (>10 kW), necessary for sufficient neutron flux. In off-line circulation tests, the liquid-lithium loop generated a stable lithium jet at high velocity, on a concave supporting wall; the concept will first be tested using a high-power electron beam impinging on the lithium jet. High intensity proton beam irradiation (1.91-2.5 MeV, 2-4 mA) will take place at Soreq Applied Research Accelerator Facility (SARAF) superconducting linear accelerator currently in construction at SNRC. Radiological risks due to the (7)Be produced in the reaction were studied and will be handled through a proper design, including a cold trap and appropriate shielding. A moderator/reflector assembly is planned according to a Monte Carlo simulation, to create a neutron spectrum and intensity maximally effective to the treatment and to reduce prompt gamma radiation dose risks. Copyright © 2011 Elsevier Ltd. All rights reserved.

  17. Automated planning target volume generation: an evaluation pitting a computer-based tool against human experts

    International Nuclear Information System (INIS)

    Ketting, Case H.; Austin-Seymour, Mary; Kalet, Ira; Jacky, Jon; Kromhout-Schiro, Sharon; Hummel, Sharon; Unger, Jonathan; Fagan, Lawrence M.; Griffin, Tom

    1997-01-01

    Purpose: Software tools are seeing increased use in three-dimensional treatment planning. However, the development of these tools frequently omits careful evaluation before placing them in clinical use. This study demonstrates the application of a rigorous evaluation methodology using blinded peer review to an automated software tool that produces ICRU-50 planning target volumes (PTVs). Methods and Materials: Seven physicians from three different institutions involved in three-dimensional treatment planning participated in the evaluation. Four physicians drew partial PTVs on nine test cases, consisting of four nasopharynx and five lung primaries. Using the same information provided to the human experts, the computer tool generated PTVs for comparison. The remaining three physicians, designated evaluators, individually reviewed the PTVs for acceptability. To exclude bias, the evaluators were blinded to the source (human or computer) of the PTVs they reviewed. Their scorings of the PTVs were statistically examined to determine if the computer tool performed as well as the human experts. Results: The computer tool was as successful as the human experts in generating PTVs. Failures were primarily attributable to insufficient margins around the clinical target volume and to encroachment upon critical structures. In a qualitative analysis, the human and computer experts displayed similar types and distributions of errors. Conclusions: Rigorous evaluation of computer-based radiotherapy tools requires comparison to current practice and can reveal areas for improvement before the tool enters clinical practice

  18. Risk-Based Treatment Targets for Onsite Non-Potable Water ...

    Science.gov (United States)

    This presentation presents risk-based enteric pathogen log reduction targets for non-potable and potable uses of a variety of alternative source waters (i.e., municipal wastewater, locally-collected greywater, rainwater, and stormwater). A probabilistic, forward Quantitative Microbial Risk Assessment (QMRA) was used to derive the pathogen log10 reduction targets (LRTs) that corresponded with an infection risk of either 10-4 per person per year (ppy) or 10-2 ppy. The QMRA accounted for variation in pathogen concentration and sporadic pathogen occurrence (when data were available) in source waters for reference pathogens Rotavirus, Adenovirus, Norovirus, Campylobacter spp., Salmonella spp., Giardia spp., and Cryptosporidium spp.. Non-potable uses included indoor use (for toilet flushing and clothes washing) with accidental ingestion of treated non-potable water (or cross connection with potable water), and unrestricted irrigation for outdoor use. Various exposure scenarios captured the uncertainty from key inputs, i.e., the pathogen concentration in source water; the volume of water ingested; and for the indoor use, the frequency of and the fraction of the population exposed to accidental ingestion. Both potable and non-potable uses required pathogen treatment for the selected waters and the LRT was generally greater for potable use than nonpotable indoor use and unrestricted irrigation. The difference in treatment requirements among source waters was driven by th

  19. SUPERPIXEL BASED FACTOR ANALYSIS AND TARGET TRANSFORMATION METHOD FOR MARTIAN MINERALS DETECTION

    Directory of Open Access Journals (Sweden)

    X. Wu

    2018-04-01

    Full Text Available The Factor analysis and target transformation (FATT is an effective method to test for the presence of particular mineral on Martian surface. It has been used both in thermal infrared (Thermal Emission Spectrometer, TES and near-infrared (Compact Reconnaissance Imaging Spectrometer for Mars, CRISM hyperspectral data. FATT derived a set of orthogonal eigenvectors from a mixed system and typically selected first 10 eigenvectors to least square fit the library mineral spectra. However, minerals present only in a limited pixels will be ignored because its weak spectral features compared with full image signatures. Here, we proposed a superpixel based FATT method to detect the mineral distributions on Mars. The simple linear iterative clustering (SLIC algorithm was used to partition the CRISM image into multiple connected image regions with spectral homogeneous to enhance the weak signatures by increasing their proportion in a mixed system. A least square fitting was used in target transformation and performed to each region iteratively. Finally, the distribution of the specific minerals in image was obtained, where fitting residual less than a threshold represent presence and otherwise absence. We validate our method by identifying carbonates in a well analysed CRISM image in Nili Fossae on Mars. Our experimental results indicate that the proposed method work well both in simulated and real data sets.

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

    Science.gov (United States)

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

    2018-04-01

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

  1. Multivariate analysis for the estimation of target localization errors in fiducial marker-based radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Takamiya, Masanori [Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501, Japan and Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Nakamura, Mitsuhiro, E-mail: m-nkmr@kuhp.kyoto-u.ac.jp; Akimoto, Mami; Ueki, Nami; Yamada, Masahiro; Matsuo, Yukinori; Mizowaki, Takashi; Hiraoka, Masahiro [Department of Radiation Oncology and Image-applied Therapy, Graduate School of Medicine, Kyoto University, Kyoto 606-8507 (Japan); Tanabe, Hiroaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe 650-0047 (Japan); Kokubo, Masaki [Division of Radiation Oncology, Institute of Biomedical Research and Innovation, Kobe 650-0047, Japan and Department of Radiation Oncology, Kobe City Medical Center General Hospital, Kobe 650-0047 (Japan); Itoh, Akio [Department of Nuclear Engineering, Graduate School of Engineering, Kyoto University, Kyoto 606-8501 (Japan)

    2016-04-15

    Purpose: To assess the target localization error (TLE) in terms of the distance between the target and the localization point estimated from the surrogates (|TMD|), the average of respiratory motion for the surrogates and the target (|aRM|), and the number of fiducial markers used for estimating the target (n). Methods: This study enrolled 17 lung cancer patients who subsequently underwent four fractions of real-time tumor tracking irradiation. Four or five fiducial markers were implanted around the lung tumor. The three-dimensional (3D) distance between the tumor and markers was at maximum 58.7 mm. One of the markers was used as the target (P{sub t}), and those markers with a 3D |TMD{sub n}| ≤ 58.7 mm at end-exhalation were then selected. The estimated target position (P{sub e}) was calculated from a localization point consisting of one to three markers except P{sub t}. Respiratory motion for P{sub t} and P{sub e} was defined as the root mean square of each displacement, and |aRM| was calculated from the mean value. TLE was defined as the root mean square of each difference between P{sub t} and P{sub e} during the monitoring of each fraction. These procedures were performed repeatedly using the remaining markers. To provide the best guidance on the answer with n and |TMD|, fiducial markers with a 3D |aRM ≥ 10 mm were selected. Finally, a total of 205, 282, and 76 TLEs that fulfilled the 3D |TMD| and 3D |aRM| criteria were obtained for n = 1, 2, and 3, respectively. Multiple regression analysis (MRA) was used to evaluate TLE as a function of |TMD| and |aRM| in each n. Results: |TMD| for n = 1 was larger than that for n = 3. Moreover, |aRM| was almost constant for all n, indicating a similar scale for the marker’s motion near the lung tumor. MRA showed that |aRM| in the left–right direction was the major cause of TLE; however, the contribution made little difference to the 3D TLE because of the small amount of motion in the left–right direction. The TLE

  2. VEGF targeting in mesotheliomas using an interleukin-6 signal inhibitor based on adenovirus gene delivery.

    Science.gov (United States)

    Adachi, Yasuo; Yoshio-Hoshino, Naoko; Aoki, Chieko; Nishimoto, Norihiro

    2010-06-01

    Malignant mesotheliomas reportedly secrete interleukin-6 (IL-6) which augments production of vascular endothelial growth factor (VEGF) from mesothelioma cells. We previously reported the development of a new receptor inhibitor of IL-6 (NRI) by genetically engineering tocilizumab, a humanized anti-IL-6 receptor monoclonal antibody. Since NRI is encoded on a single gene, it is easily applicable to a gene delivery system using virus vehicles. In this study, we report VEGF targeting through NRI expression based on adenovirus-mediated gene delivery in mesothelioma cells. We constructed an NRI expression vector in the context of a tropism-modified adenovirus vector that had enhanced infectivity in mesothelioma cells. This virus effectively induced NRI secretion from mesothelioma cells. This virus infection also reduced the VEGF production in mesothelioma cells. These results indicate that NRI shows potential as an agent in the treatment of mesotheliomas.

  3. Photodynamic therapy and imaging based on tumor-targeted nanoprobe, polymer-conjugated zinc protoporphyrin

    Science.gov (United States)

    Fang, Jun; Liao, Long; Yin, Hongzhuan; Nakamura, Hideaki; Subr, Vladimir; Ulbrich, Karel; Maeda, Hiroshi

    2015-01-01

    Aim: To evaluate the potential of tumor-targeted nanoprobe, N-(2-hydroxypropyl)methacrylamide copolymer-conjugated zinc protoporphyrin (PZP) for photodynamic therapy (PDT) and tumor imaging. Materials & Methods: Different tumor models including carcinogen-induced cancer were used, PZP was intravenously injected followed by irradiation with xenon or blue fluorescent light on tumor. Results: One PZP 20 mg/kg (ZnPP equivalent) dose with two or three treatments of light at an intensity of ≥20 J/cm2 caused necrosis and disappearance of most tumors (>70%) in different tumor models. We also confirmed PZP-based tumor imaging in carcinogen-induced breast tumor and colon cancer models. Conclusion: These findings support the potential application of PZP as a tumor-selective nanoprobe for PDT as well as tumor imaging, by virtue of the enhanced permeability and retention effect. PMID:28031879

  4. Construction of Target Controllable Image Segmentation Model Based on Homotopy Perturbation Technology

    Directory of Open Access Journals (Sweden)

    Shu-Li Mei

    2013-01-01

    Full Text Available Based on the basic idea of the homotopy perturbation method which was proposed by Jihuan He, a target controllable image segmentation model and the corresponding multiscale wavelet numerical method are constructed. Using the novel model, we can get the only right object from the multiobject images, which is helpful to avoid the oversegmentation and insufficient segmentation. The solution of the variational model is the nonlinear PDEs deduced by the variational approach. So, the bottleneck of the variational model on image segmentation is the lower efficiency of the algorithm. Combining the multiscale wavelet interpolation operator and HPM, a semianalytical numerical method can be obtained, which can improve the computational efficiency and accuracy greatly. The numerical results on some images segmentation show that the novel model and the numerical method are effective and practical.

  5. Image and video based remote target localization and tracking on smartphones

    Science.gov (United States)

    Wang, Qia; Lobzhanidze, Alex; Jang, Hyun; Zeng, Wenjun; Shang, Yi; Yang, Jingyu

    2012-06-01

    Smartphones are becoming popular nowadays not only because of its communication functionality but also, more importantly, its powerful sensing and computing capability. In this paper, we describe a novel and accurate image and video based remote target localization and tracking system using the Android smartphones, by leveraging its built-in sensors such as camera, digital compass, GPS, etc. Even though many other distance estimation or localization devices are available, our all-in-one, easy-to-use localization and tracking system on low cost and commodity smartphones is first of its kind. Furthermore, smartphones' exclusive user-friendly interface has been effectively taken advantage of by our system to facilitate low complexity and high accuracy. Our experimental results show that our system works accurately and efficiently.

  6. Water based suspensions of iron oxide obtained by laser target evaporation for biomedical applications

    Science.gov (United States)

    Novoselova, I. P.; Safronov, A. P.; Samatov, O. M.; Beketov, I. V.; Medvedev, A. I.; Kurlyandskaya, G. V.

    2016-10-01

    In this work spherical magnetic nanoparticles (MNPs) of iron oxide were obtained by laser target evaporation technique (LTE). Water based suspensions were prepared on the basis of obtained MNPs and their properties were also studied including inductive heat capacity. Their structure and properties were studied by a number of techniques including magnetometry and heat capacity measurements. Magnetic induction heating experiment show the specific loss power (SLP) value in the narrow range from 1.30 to 1.45 W/g for all samples under consideration when using alternating magnetic field of 1.7 kA/m and frequency of 210 kHz. These parameters insure that LTE MNPs are interesting materials promising for magnetic fluid hyperthermia.

  7. A Camp-based Intervention Targeting Independence Among Individuals with Spina Bifida

    Science.gov (United States)

    O’Mahar, Kerry; Jandasek, Barbara; Zukerman, Jill

    2010-01-01

    Objective To design and evaluate a camp-based intervention, the goal of which was to increase independence among children, adolescents, and adults with spina bifida. Methods An intervention targeting independence was embedded within a typical week long camp experience. The intervention consisted of the following: collaborative (i.e., parent and camper) goal identification, group sessions consisting of psycho-education and cognitive tools, and goal monitoring by camp counselors. Camper and parent report of demographic variables, goal attainment, spina bifida knowledge, and independence were gathered. Interventionist report of adherence to the treatment manual was also collected. Results Campers made significant gains in individual goals, management of spina bifida responsibilities, and independence with general spina bifida tasks, with medium effect sizes observed in goal attainment. Conclusions Results indicated that significant progress was made on individually oriented goals from pre- to post-camp. Design issues are discussed. PMID:20026569

  8. Microenvironment of Tumor-Draining Lymph Nodes: Opportunities for Liposome-Based Targeted Therapy

    Directory of Open Access Journals (Sweden)

    Siddarth Chandrasekaran

    2014-11-01

    Full Text Available The World Health Organization (WHO recently reported that the total number of global cancer cases in 2013 reached 14 million, a 10% rise since 2008, while the total number of cancer deaths reached 8.2 million, a 5.2% increase since 2008. Metastasis is the major cause of death from cancer, accounting for 90% of all cancer related deaths. Tumor-draining lymph nodes (TDLN, the sentinel nodes, are the first organs of metastasis in several types of cancers. The extent of metastasis in the TDLN is often used in disease staging and prognosis evaluation in cancer patients. Here, we describe the microenvironment of the TDLN and review the recent literature on liposome-based therapies directed to immune cells within the TDLN with the intent to target cancer cells.

  9. Claudins Overexpression in Ovarian Cancer: Potential Targets for Clostridium Perfringens Enterotoxin (CPE Based Diagnosis and Therapy

    Directory of Open Access Journals (Sweden)

    Diana P. English

    2013-05-01

    Full Text Available Claudins are a family of tight junction proteins regulating paracellular permeability and cell polarity with different patterns of expression in benign and malignant human tissues. There are approximately 27 members of the claudin family identified to date with varying cell and tissue-specific expression. Claudins-3, -4 and -7 represent the most highly differentially expressed claudins in ovarian cancer. While their exact role in ovarian tumors is still being elucidated, these proteins are thought to be critical for ovarian cancer cell invasion/dissemination and resistance to chemotherapy. Claudin-3 and claudin-4 are the natural receptors for the Clostridium perfringens enterotoxin (CPE, a potent cytolytic toxin. These surface proteins may therefore represent attractive targets for the detection and treatment of chemotherapy-resistant ovarian cancer and other aggressive solid tumors overexpressing claudin-3 and -4 using CPE-based theranostic agents.

  10. RNAi-based targeted gene knockdown in the model oleaginous microalgae Nannochloropsis oceanica.

    Science.gov (United States)

    Wei, Li; Xin, Yi; Wang, Qintao; Yang, Juan; Hu, Hanhua; Xu, Jian

    2017-03-01

    Microalgae are promising feedstock for renewable fuels such as biodiesel, yet development of industrial oleaginous strains has been hindered by the paucity and inefficiency of reverse genetics tools. Here we established an efficient RNAi-based targeted gene-knockdown method for Nannochloropsis spp., which are emerging model organisms for industrial microalgal oil production. The method achieved a 40-80% success rate in Nannochloropsis oceanica strain IMET1. When transcript level of one carbonic anhydrase (CA) was inhibited by 62-83% via RNAi, mutant cells exhibited photosynthetic oxygen evolution (POE) rates that were 68-100% higher than wild-type (WT) at pH 6.0, equivalent to WT at pH 8.2, yet 39-45% lower than WT at pH 9.0. Moreover, the mutant POE rates were negatively correlated with the increase of culture pH, an exact opposite of WT. Thus, a dynamic carbon concentration mechanism (CCM) that is highly sensitive to pH homeostasis was revealed, where the CA inhibition likely partially abrogated the mechanism that normally deactivates CCM under a high level of dissolved CO 2 . Extension of the method to another sequenced N. oceanica strain of CCMP 1779 demonstrated comparable performance. Finally, McrBC-PCR followed by bisulfite sequencing revealed that the gene knockdown is mediated by the CG, CHG and CHH types of DNA methylation at the coding region of the targeted gene. The efficiency, robustness and general applicability of this reverse genetics approach suggested the possibility of large-scale RNAi-based gene function screening in industrial microalgae. © 2016 The Authors The Plant Journal © 2016 John Wiley & Sons Ltd.

  11. Muscarinic receptors as model targets and antitargets for structure-based ligand discovery.

    Science.gov (United States)

    Kruse, Andrew C; Weiss, Dahlia R; Rossi, Mario; Hu, Jianxin; Hu, Kelly; Eitel, Katrin; Gmeiner, Peter; Wess, Jürgen; Kobilka, Brian K; Shoichet, Brian K

    2013-10-01

    G protein-coupled receptors (GPCRs) regulate virtually all aspects of human physiology and represent an important class of therapeutic drug targets. Many GPCR-targeted drugs resemble endogenous agonists, often resulting in poor selectivity among receptor subtypes and restricted pharmacologic profiles. The muscarinic acetylcholine receptor family exemplifies these problems; thousands of ligands are known, but few are receptor subtype-selective and nearly all are cationic in nature. Using structure-based docking against the M2 and M3 muscarinic receptors, we screened 3.1 million molecules for ligands with new physical properties, chemotypes, and receptor subtype selectivities. Of 19 docking-prioritized molecules tested against the M2 subtype, 11 had substantial activity and 8 represented new chemotypes. Intriguingly, two were uncharged ligands with low micromolar to high nanomolar Ki values, an observation with few precedents among aminergic GPCRs. To exploit a single amino-acid substitution among the binding pockets between the M2 and M3 receptors, we selected molecules predicted by docking to bind to the M3 and but not the M2 receptor. Of 16 molecules tested, 8 bound to the M3 receptor. Whereas selectivity remained modest for most of these, one was a partial agonist at the M3 receptor without measurable M2 agonism. Consistent with this activity, this compound stimulated insulin release from a mouse β-cell line. These results support the ability of structure-based discovery to identify new ligands with unexplored chemotypes and physical properties, leading to new biologic functions, even in an area as heavily explored as muscarinic pharmacology.

  12. SciMiner: web-based literature mining tool for target identification and functional enrichment analysis.

    Science.gov (United States)

    Hur, Junguk; Schuyler, Adam D; States, David J; Feldman, Eva L

    2009-03-15

    SciMiner is a web-based literature mining and functional analysis tool that identifies genes and proteins using a context specific analysis of MEDLINE abstracts and full texts. SciMiner accepts a free text query (PubMed Entrez search) or a list of PubMed identifiers as input. SciMiner uses both regular expression patterns and dictionaries of gene symbols and names compiled from multiple sources. Ambiguous acronyms are resolved by a scoring scheme based on the co-occurrence of acronyms and corresponding description terms, which incorporates optional user-defined filters. Functional enrichment analyses are used to identify highly relevant targets (genes and proteins), GO (Gene Ontology) terms, MeSH (Medical Subject Headings) terms, pathways and protein-protein interaction networks by comparing identified targets from one search result with those from other searches or to the full HGNC [HUGO (Human Genome Organization) Gene Nomenclature Committee] gene set. The performance of gene/protein name identification was evaluated using the BioCreAtIvE (Critical Assessment of Information Extraction systems in Biology) version 2 (Year 2006) Gene Normalization Task as a gold standard. SciMiner achieved 87.1% recall, 71.3% precision and 75.8% F-measure. SciMiner's literature mining performance coupled with functional enrichment analyses provides an efficient platform for retrieval and summary of rich biological information from corpora of users' interests. http://jdrf.neurology.med.umich.edu/SciMiner/. A server version of the SciMiner is also available for download and enables users to utilize their institution's journal subscriptions. Supplementary data are available at Bioinformatics online.

  13. Target tracking system based on preliminary and precise two-stage compound cameras

    Science.gov (United States)

    Shen, Yiyan; Hu, Ruolan; She, Jun; Luo, Yiming; Zhou, Jie

    2018-02-01

    Early detection of goals and high-precision of target tracking is two important performance indicators which need to be balanced in actual target search tracking system. This paper proposed a target tracking system with preliminary and precise two - stage compound. This system using a large field of view to achieve the target search. After the target was searched and confirmed, switch into a small field of view for two field of view target tracking. In this system, an appropriate filed switching strategy is the key to achieve tracking. At the same time, two groups PID parameters are add into the system to reduce tracking error. This combination way with preliminary and precise two-stage compound can extend the scope of the target and improve the target tracking accuracy and this method has practical value.

  14. Homology model-based virtual screening for GPCR ligands using docking and target-biased scoring.

    Science.gov (United States)

    Radestock, Sebastian; Weil, Tanja; Renner, Steffen

    2008-05-01

    The current study investigates the combination of two recently reported techniques for the improvement of homology model-based virtual screening for G-protein coupled receptor (GPCR) ligands. First, ligand-supported homology modeling was used to generate receptor models that were in agreement with mutagenesis data and structure-activity relationship information of the ligands. Second, interaction patterns from known ligands to the receptor were applied for scoring and rank ordering compounds from a virtual library using ligand-receptor interaction fingerprint-based similarity (IFS). Our approach was evaluated in retrospective virtual screening experiments for antagonists of the metabotropic glutamate receptor (mGluR) subtype 5. The results of our approach were compared to the results obtained by conventional scoring functions (Dock-Score, PMF-Score, Gold-Score, ChemScore, and FlexX-Score). The IFS lead to significantly higher enrichment rates, relative to the competing scoring functions. Though using a target-biased scoring approach, the results were not biased toward the chemical classes of the reference structures. Our results indicate that the presented approach has the potential to serve as a general setup for successful structure-based GPCR virtual screening.

  15. Connecticut's Value-Based Insurance Plan Increased The Use Of Targeted Services And Medication Adherence.

    Science.gov (United States)

    Hirth, Richard A; Cliff, Elizabeth Q; Gibson, Teresa B; McKellar, M Richard; Fendrick, A Mark

    2016-04-01

    In 2011 Connecticut implemented the Health Enhancement Program for state employees. This voluntary program followed the principles of value-based insurance design (VBID) by lowering patient costs for certain high-value primary and chronic disease preventive services, coupled with requirements that enrollees receive these services. Nonparticipants in the program, including those removed for noncompliance with its requirements, were assessed a premium surcharge. The program was intended to curb cost growth and improve health through adherence to evidence-based preventive care. To evaluate its efficacy in doing so, we compared changes in service use and spending after implementation of the program to trends among employees of six other states. Compared to employees of other states, Connecticut employees were similar in age and sex but had a slightly higher percentage of enrollees with chronic conditions and substantially higher spending at baseline. During the program's first two years, the use of targeted services and adherence to medications for chronic conditions increased, while emergency department use decreased, relative to the situation in the comparison states. The program's impact on costs was inconclusive and requires a longer follow-up period. This novel combination of VBID principles and participation requirements may be a tool that can help plan sponsors increase the use of evidence-based preventive services. Project HOPE—The People-to-People Health Foundation, Inc.

  16. Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Ran, E-mail: jliubme@tsinghua.edu.cn, E-mail: liuran@tsinghua.edu.cn; Liu, Jing, E-mail: jliubme@tsinghua.edu.cn, E-mail: liuran@tsinghua.edu.cn [Department of Biomedical Engineering, School of Medicine, Tsinghua University, Beijing 100084 (China); Wang, Jia [Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21218 (United States)

    2015-07-15

    Hyperthermia (42-46°C), treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated to quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR) based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl) than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures.

  17. Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

    Science.gov (United States)

    Liu, Ran; Wang, Jia; Liu, Jing

    2015-07-01

    Hyperthermia (42-46°C), treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated to quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR) based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl) than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures.

  18. Thermal infrared images to quantify thermal ablation effects of acid and base on target tissues

    International Nuclear Information System (INIS)

    Liu, Ran; Liu, Jing; Wang, Jia

    2015-01-01

    Hyperthermia (42-46°C), treatment of tumor tissue through elevated temperature, offers several advantages including high cost-effectiveness, highly targeted ablation and fewer side effects and hence higher safety level over traditional therapies such as chemotherapy and radiotherapy. Recently, hyperthermia using heat release through exothermic acid-base neutralization comes into view owing to its relatively safe products of salt and water and highly confined ablation. However, lack of quantitative understanding of the spatial and temporal temperature profiles that are produced by simultaneous diffusion of liquid chemical and its chemical reaction within tumor tissue impedes the application of this method. This article is dedicated to quantify thermal ablation effects of acid and base both individually and as in neutralization via infrared captured thermal images. A theoretical model is used to approximate specific heat absorption rate (SAR) based on experimental measurements that contrast two types of tissue, normal pork and pig liver. According to the computation, both pork and liver tissue has a higher ability in absorbing hydrochloric acid (HCl) than sodium hydroxide, hence suggesting that a reduced dosage for HCl is appropriate in a surgery. The heating effect depends heavily on the properties of tissue types and amount of chemical reagents administered. Given thermal parameters such as SAR for different tissues, a computational model can be made in predicting temperature transitions which will be helpful in planning and optimizing surgical hyperthermia procedures

  19. Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies

    Directory of Open Access Journals (Sweden)

    Erhard Hofer

    2017-07-01

    Full Text Available Immunotherapies based on natural killer (NK cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell system. Infections and malignant diseases can further lead to the shaping of NK cell populations with altered reactivity. Counter measures of potential therapeutic impact include the blocking of inhibitory interactions between NK cell receptors and their cellular ligands, the enhancement of activating receptor signals, and the infusion of large numbers of ex vivo generated and selected NK cells. Moreover, the specific cross-linking of NK cells to their target cells using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents is a promising approach. In this context, NK cells stand out by their positive effects and safety demonstrated in most clinical trials so far. Based in part on results of the recent EC-sponsored project “NATURIMMUN” and considering additional published work in the field, we discuss below new developments and future directions that have the potential to further advance and establish NK cell-based therapies at the clinics on a broader scale.

  20. Natural Killer Cell-Based Cancer Immunotherapies: From Immune Evasion to Promising Targeted Cellular Therapies.

    Science.gov (United States)

    Hofer, Erhard; Koehl, Ulrike

    2017-01-01

    Immunotherapies based on natural killer (NK) cells are among the most promising therapies under development for the treatment of so far incurable forms of leukemia and other types of cancer. The importance of NK cells for the control of viral infections and cancer is supported among others by the findings that viruses and tumors use a multitude of mechanisms to subvert and evade the NK cell system. Infections and malignant diseases can further lead to the shaping of NK cell populations with altered reactivity. Counter measures of potential therapeutic impact include the blocking of inhibitory interactions between NK cell receptors and their cellular ligands, the enhancement of activating receptor signals, and the infusion of large numbers of ex vivo generated and selected NK cells. Moreover, the specific cross-linking of NK cells to their target cells using chimeric antigen receptors or therapeutic bi-/trispecific antibody reagents is a promising approach. In this context, NK cells stand out by their positive effects and safety demonstrated in most clinical trials so far. Based in part on results of the recent EC-sponsored project "NATURIMMUN" and considering additional published work in the field, we discuss below new developments and future directions that have the potential to further advance and establish NK cell-based therapies at the clinics on a broader scale.

  1. A Narrative Review of Social Media and Game-Based Nutrition Interventions Targeted at Young Adults.

    Science.gov (United States)

    Nour, Monica; Yeung, Sin Hang; Partridge, Stephanie; Allman-Farinelli, Margaret

    2017-05-01

    The increased popularity of social media and mobile gaming among young adults provides an opportunity for innovative nutrition programs. This review evaluated the efficacy of these strategies in interventions targeted at 18- to 35-year-olds. The protocol was guided by the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Ten scientific databases, information technology conference proceedings, and gray literature were searched. Two reviewers conducted screening, data extraction, and quality assessments. Interventions were included if they used social media or electronic games. Comparisons were made pre- to post-intervention, or between intervention and control arms. Outcomes of interest included change in nutrition knowledge, attitudes, behavior, or weight and/or body composition. Eleven social media-based (randomized controlled trials [RCT] n=7) and six game-based [RCT n=1]) interventions were included. Overall quality of studies was low. Social media-based strategies included forum/blogs (n=5), Facebook (n=5), Twitter (n=1), YouTube (n=1), and chat rooms (n=1). Eight (RCT n=6) of 11 social media-based studies demonstrated improvements in outcomes. Findings suggested that social media may be more effective when combined with other strategies. Virtual reality games (n=3), web-based games (n=2), and a mobile application (n=1) were used in the gaming interventions. While a significant increase in knowledge was reported by three gaming studies (RCT=1), two used nonvalidated tools and longer-term measures of weight and behavioral outcomes were limited. The use of social media and gaming for nutrition promotion is in its infancy. Preliminary evidence suggests that these strategies have some utility for intervening with young adults. Further research using high-quality study designs is required, with measurement of outcomes over longer time periods. The systematic review protocol is registered with PROSPERO (registration number: CRD42015025427

  2. Identification of targets of miR-200b by a SILAC-based quantitative proteomic approach

    Directory of Open Access Journals (Sweden)

    Arivusudar Marimuthu

    2014-09-01

    Full Text Available miRNAs regulate gene expression by binding to cognate mRNAs causing mRNA degradation or translational repression. Mass spectrometry-based proteomic analysis is being widely used to identify miRNA targets. The miR-200b miRNA cluster is often overexpressed in multiple cancer types, but the identity of the targets remains elusive. Using SILAC-based analysis, we examined the effects of overexpression of a miR-200b mimic or a control miRNA in fibrosarcoma cells. We identified around 300 potential targets of miR-200b based on a change in the expression of protein levels. We validated a subset of potential targets at the transcript level using quantitative PCR.

  3. Integration of bio-inspired, control-based visual and olfactory data for the detection of an elusive target

    Science.gov (United States)

    Duong, Tuan A.; Duong, Nghi; Le, Duong

    2017-01-01

    In this paper, we present an integration technique using a bio-inspired, control-based visual and olfactory receptor system to search for elusive targets in practical environments where the targets cannot be seen obviously by either sensory data. Bio-inspired Visual System is based on a modeling of extended visual pathway which consists of saccadic eye movements and visual pathway (vertebrate retina, lateral geniculate nucleus and visual cortex) to enable powerful target detections of noisy, partial, incomplete visual data. Olfactory receptor algorithm, namely spatial invariant independent component analysis, that was developed based on data of old factory receptor-electronic nose (enose) of Caltech, is adopted to enable the odorant target detection in an unknown environment. The integration of two systems is a vital approach and sets up a cornerstone for effective and low-cost of miniaturized UAVs or fly robots for future DOD and NASA missions, as well as for security systems in Internet of Things environments.

  4. Large-scale identification of potential drug targets based on the topological features of human protein-protein interaction network.

    Science.gov (United States)

    Li, Zhan-Chao; Zhong, Wen-Qian; Liu, Zhi-Qing; Huang, Meng-Hua; Xie, Yun; Dai, Zong; Zou, Xiao-Yong

    2015-04-29

    Identifying potential drug target proteins is a crucial step in the process of drug discovery and plays a key role in the study of the molecular mechanisms of disease. Based on the fact that the majority of proteins exert their functions through interacting with each other, we propose a method to recognize target proteins by using the human protein-protein interaction network and graph theory. In the network, vertexes and edges are weighted by using the confidence scores of interactions and descriptors of protein primary structure, respectively. The novel network topological features are defined and employed to characterize protein using existing databases. A widely used minimum redundancy maximum relevance and random forests algorithm are utilized to select the optimal feature subset and construct model for the identification of potential drug target proteins at the proteome scale. The accuracies of training set and test set are 89.55% and 85.23%. Using the constructed model, 2127 potential drug target proteins have been recognized and 156 drug target proteins have been validated in the database of drug target. In addition, some new drug target proteins can be considered as targets for treating diseases of mucopolysaccharidosis, non-arteritic anterior ischemic optic neuropathy, Bernard-Soulier syndrome and pseudo-von Willebrand, etc. It is anticipated that the proposed method may became a powerful high-throughput virtual screening tool of drug target. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF

    Energy Technology Data Exchange (ETDEWEB)

    Baz-Lomba, J.A., E-mail: jba@niva.no [Norwegian Institute for Water Research, Gaustadalléen 21, NO-0349, Oslo (Norway); Faculty of Medicine, University of Oslo, PO box 1078 Blindern, 0316, Oslo (Norway); Reid, Malcolm J.; Thomas, Kevin V. [Norwegian Institute for Water Research, Gaustadalléen 21, NO-0349, Oslo (Norway)

    2016-03-31

    The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS{sup e}. Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4–187 ng L{sup −1}). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS{sup e} data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. - Highlights: • A novel reiterative workflow

  6. Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF

    International Nuclear Information System (INIS)

    Baz-Lomba, J.A.; Reid, Malcolm J.; Thomas, Kevin V.

    2016-01-01

    The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS e . Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4–187 ng L −1 ). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS e data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. - Highlights: • A novel reiterative workflow based on three

  7. Targeted genetic testing for familial hypercholesterolaemia using next generation sequencing: a population-based study

    Science.gov (United States)

    2014-01-01

    Background Familial hypercholesterolaemia (FH) is a common Mendelian condition which, untreated, results in premature coronary heart disease. An estimated 88% of FH cases are undiagnosed in the UK. We previously validated a method for FH mutation detection in a lipid clinic population using next generation sequencing (NGS), but this did not address the challenge of identifying index cases in primary care where most undiagnosed patients receive healthcare. Here, we evaluate the targeted use of NGS as a potential route to diagnosis of FH in a primary care population subset selected for hypercholesterolaemia. Methods We used microfluidics-based PCR amplification coupled with NGS and multiplex ligation-dependent probe amplification (MLPA) to detect mutations in LDLR, APOB and PCSK9 in three phenotypic groups within the Generation Scotland: Scottish Family Health Study including 193 individuals with high total cholesterol, 232 with moderately high total cholesterol despite cholesterol-lowering therapy, and 192 normocholesterolaemic controls. Results Pathogenic mutations were found in 2.1% of hypercholesterolaemic individuals, in 2.2% of subjects on cholesterol-lowering therapy and in 42% of their available first-degree relatives. In addition, variants of uncertain clinical significance (VUCS) were detected in 1.4% of the hypercholesterolaemic and cholesterol-lowering therapy groups. No pathogenic variants or VUCS were detected in controls. Conclusions We demonstrated that population-based genetic testing using these protocols is able to deliver definitive molecular diagnoses of FH in individuals with high cholesterol or on cholesterol-lowering therapy. The lower cost and labour associated with NGS-based testing may increase the attractiveness of a population-based approach to FH detection compared to genetic testing with conventional sequencing. This could provide one route to increasing the present low percentage of FH cases with a genetic diagnosis. PMID:24956927

  8. Target and suspect screening of psychoactive substances in sewage-based samples by UHPLC-QTOF.

    Science.gov (United States)

    Baz-Lomba, J A; Reid, Malcolm J; Thomas, Kevin V

    2016-03-31

    The quantification of illicit drug and pharmaceutical residues in sewage has been shown to be a valuable tool that complements existing approaches in monitoring the patterns and trends of drug use. The present work delineates the development of a novel analytical tool and dynamic workflow for the analysis of a wide range of substances in sewage-based samples. The validated method can simultaneously quantify 51 target psychoactive substances and pharmaceuticals in sewage-based samples using an off-line automated solid phase extraction (SPE-DEX) method, using Oasis HLB disks, followed by ultra-high performance liquid chromatography coupled to quadrupole time-of-flight mass spectrometry (UHPLC-QTOF) in MS(e). Quantification and matrix effect corrections were overcome with the use of 25 isotopic labeled internal standards (ILIS). Recoveries were generally greater than 60% and the limits of quantification were in the low nanogram-per-liter range (0.4-187 ng L(-1)). The emergence of new psychoactive substances (NPS) on the drug scene poses a specific analytical challenge since their market is highly dynamic with new compounds continuously entering the market. Suspect screening using high-resolution mass spectrometry (HRMS) simultaneously allowed the unequivocal identification of NPS based on a mass accuracy criteria of 5 ppm (of the molecular ion and at least two fragments) and retention time (2.5% tolerance) using the UNIFI screening platform. Applying MS(e) data against a suspect screening database of over 1000 drugs and metabolites, this method becomes a broad and reliable tool to detect and confirm NPS occurrence. This was demonstrated through the HRMS analysis of three different sewage-based sample types; influent wastewater, passive sampler extracts and pooled urine samples resulting in the concurrent quantification of known psychoactive substances and the identification of NPS and pharmaceuticals. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. PLS-based and regularization-based methods for the selection of relevant variables in non-targeted metabolomics data

    Directory of Open Access Journals (Sweden)

    Renata Bujak

    2016-07-01

    Full Text Available Non-targeted metabolomics constitutes a part of systems biology and aims to determine many metabolites in complex biological samples. Datasets obtained in non-targeted metabolomics studies are multivariate and high-dimensional due to the sensitivity of mass spectrometry-based detection methods as well as complexity of biological matrices. Proper selection of variables which contribute into group classification is a crucial step, especially in metabolomics studies which are focused on searching for disease biomarker candidates. In the present study, three different statistical approaches were tested using two metabolomics datasets (RH and PH study. Orthogonal projections to latent structures-discriminant analysis (OPLS-DA without and with multiple testing correction as well as least absolute shrinkage and selection operator (LASSO were tested and compared. For the RH study, OPLS-DA model built without multiple testing correction, selected 46 and 218 variables based on VIP criteria using Pareto and UV scaling, respectively. In the case of the PH study, 217 and 320 variables were selected based on VIP criteria using Pareto and UV scaling, respectively. In the RH study, OPLS-DA model built with multiple testing correction, selected 4 and 19 variables as statistically significant in terms of Pareto and UV scaling, respectively. For PH study, 14 and 18 variables were selected based on VIP criteria in terms of Pareto and UV scaling, respectively. Additionally, the concept and fundaments of the least absolute shrinkage and selection operator (LASSO with bootstrap procedure evaluating reproducibility of results, was demonstrated. In the RH and PH study, the LASSO selected 14 and 4 variables with reproducibility between 99.3% and 100%. However, apart from the popularity of PLS-DA and OPLS-DA methods in metabolomics, it should be highlighted that they do not control type I or type II error, but only arbitrarily establish a cut-off value for PLS-DA loadings

  10. Moving-Target Position Estimation Using GPU-Based Particle Filter for IoT Sensing Applications

    Directory of Open Access Journals (Sweden)

    Seongseop Kim

    2017-11-01

    Full Text Available A particle filter (PF has been introduced for effective position estimation of moving targets for non-Gaussian and nonlinear systems. The time difference of arrival (TDOA method using acoustic sensor array has normally been used to for estimation by concealing the location of a moving target, especially underwater. In this paper, we propose a GPU -based acceleration of target position estimation using a PF and propose an efficient system and software architecture. The proposed graphic processing unit (GPU-based algorithm has more advantages in applying PF signal processing to a target system, which consists of large-scale Internet of Things (IoT-driven sensors because of the parallelization which is scalable. For the TDOA measurement from the acoustic sensor array, we use the generalized cross correlation phase transform (GCC-PHAT method to obtain the correlation coefficient of the signal using Fast Fourier Transform (FFT, and we try to accelerate the calculations of GCC-PHAT based TDOA measurements using FFT with GPU compute unified device architecture (CUDA. The proposed approach utilizes a parallelization method in the target position estimation algorithm using GPU-based PF processing. In addition, it could efficiently estimate sudden movement change of the target using GPU-based parallel computing which also can be used for multiple target tracking. It also provides scalability in extending the detection algorithm according to the increase of the number of sensors. Therefore, the proposed architecture can be applied in IoT sensing applications with a large number of sensors. The target estimation algorithm was verified using MATLAB and implemented using GPU CUDA. We implemented the proposed signal processing acceleration system using target GPU to analyze in terms of execution time. The execution time of the algorithm is reduced by 55% from to the CPU standalone operation in target embedded board, NVIDIA Jetson TX1. Also, to apply large

  11. Improved Poly (D,L-lactide) nanoparticles-based formulation for hair follicle targeting.

    Science.gov (United States)

    Fernandes, B; Silva, R; Ribeiro, A; Matamá, T; Gomes, A C; Cavaco-Paulo, A M

    2015-06-01

    Hair follicles are widely recognized as the preferential target and site of accumulation for nanoparticles after topical application. This feature is of particular importance for hair cosmetics, having the potential to refine the treatment of several hair follicle-related disorders. The aim of this work was to improve the preparation of Poly (D,L-lactide) (PLA) nanoparticles for in vivo follicular target and drug delivery. Envisaging a future industrial scale-up of the process, nanoprecipitation method was used to prepare PLA nanoparticles: the effect of several processing parameters on their properties was examined and the yield of nanoparticles formation determined. Encapsulation efficiencies and in vitro release profiles of lipophilic and hydrophilic model compounds were also assessed. In vitro cytotoxicity and ex vivo penetration studies were performed on a reference skin cell line (NCTC2455, human skin keratinocytes) and porcine skin, respectively. Using acetone : ethanol (50 : 50, v/v) as the solvent phase, 0.6% (w/w) of Pluronic(®) F68 as a surfactant agent and agitation to mix the solvent and non-solvent phases, a monodispersed population of non-cytotoxic spherical nanoparticles of approximately 150 nm was obtained. The yield of nanoparticles for this formulation was roughly 90%. After encapsulation of model compounds, no significant changes were found in the properties of particles and the entrapment efficiencies were above 80%. The release kinetics of dyes from PLA nanoparticles indicate an anomalous transport mechanism (diffusion and polymer degradation) for Nile Red (lipophilic) and a Fickian diffusion of first order for fluorescein 5(6)-isothiocyanate (hydrophilic). Ex vivo skin penetration studies confirmed the presence of nanoparticles along the entire follicular ducts. The optimized method allows the preparation of ideal PLA nanoparticles-based formulations for hair follicle targeting. PLA nanoparticles can effectively transport and release

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

    Directory of Open Access Journals (Sweden)

    Lee Sanghyuk

    2008-09-01

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

  13. Cost effectiveness of a targeted age-based West Nile virus vaccination program.

    Science.gov (United States)

    Shankar, Manjunath B; Staples, J Erin; Meltzer, Martin I; Fischer, Marc

    2017-05-25

    West Nile virus (WNV) is the leading cause of domestically-acquired arboviral disease in the United States. Several WNV vaccines are in various stages of development. We estimate the cost-effectiveness of WNV vaccination programs targeting groups at increased risk for severe WNV disease. We used a mathematical model to estimate costs and health outcomes of vaccination with WNV vaccine compared to no vaccination among seven cohorts, spaced at 10year intervals from ages 10 to 70years, each followed until 90-years-old. U.S. surveillance data were used to estimate WNV neuroinvasive disease incidence. Data for WNV seroprevalence, acute and long-term care costs of WNV disease patients, quality-adjusted life-years (QALYs), and vaccine characteristics were obtained from published reports. We assumed vaccine efficacy to either last lifelong or for 10years with booster doses given every 10years. There was a statistically significant difference in cost-effectiveness ratios across cohorts in both models and all outcomes assessed (Kruskal-Wallis test pVaccinating 70-year-olds had the lowest cost per death averted in both models at around $4.7 million (95%CI $2-$8 million). Cost per disease case averted was lowest among 40- and 50-year-old cohorts and cost per QALY saved lowest among 60-year cohorts in lifelong immunity model. The models were most sensitive to disease incidence, vaccine cost, and proportion of persons developing disease among infected. Age-based WNV vaccination program targeting those at higher risk for severe disease is more cost-effective than universal vaccination. Annual variation in WNV disease incidence, QALY weights, and vaccine costs impact the cost effectiveness ratios. Published by Elsevier Ltd.

  14. Sticky PCR: A PCR-based protocol for targeted protein engineering.

    Science.gov (United States)

    Yamabhai, Montarop

    2009-04-01

    This article describes a simple but powerful PCR-based protocol for the generation of cohesive ends on linear DNA fragments, permitting the precise engineering of DNA constructs for a variety of applications. These include the introduction of deletion mutations, domain swapping, creating hybrid DNA fusions, or targeted protein engineering. This novel method can also facilitate the cloning of large or complex DNA fragments into a relevant cloning vector independent of the use of internal restriction endonuclease sites. The protocol involves the amplification of the required fragments by polymerase chain reaction through the use of two sets of overlapping desalted oligonucleotide primers. The subsequent mixing, denaturation and re-annealing of these products present correct cohesive terminal ends for ligation. There is no requirement for special vectors, enzymes or bases, suggesting that this protocol provides a unique way of engineering constructs in a rapid and cost-effective way for specific applications, such as precise deletion or swapping of various domains of the epidermal growth factor receptor to determine their role in membrane localization.

  15. Prediction of TF target sites based on atomistic models of protein-DNA complexes

    Directory of Open Access Journals (Sweden)

    Collado-Vides Julio

    2008-10-01

    Full Text Available Abstract Background The specific recognition of genomic cis-regulatory elements by transcription factors (TFs plays an essential role in the regulation of coordinated gene expression. Studying the mechanisms determining binding specificity in protein-DNA interactions is thus an important goal. Most current approaches for modeling TF specific recognition rely on the knowledge of large sets of cognate target sites and consider only the information contained in their primary sequence. Results Here we describe a structure-based methodology for predicting sequence motifs starting from the coordinates of a TF-DNA complex. Our algorithm combines information regarding the direct and indirect readout of DNA into an atomistic statistical model, which is used to estimate the interaction potential. We first measure the ability of our method to correctly estimate the binding specificities of eight prokaryotic and eukaryotic TFs that belong to different structural superfamilies. Secondly, the method is applied to two homology models, finding that sampling of interface side-chain rotamers remarkably improves the results. Thirdly, the algorithm is compared with a reference structural method based on contact counts, obtaining comparable predictions for the experimental complexes and more accurate sequence motifs for the homology models. Conclusion Our results demonstrate that atomic-detail structural information can be feasibly used to predict TF binding sites. The computational method presented here is universal and might be applied to other systems involving protein-DNA recognition.

  16. Improvement of Hydrodynamics-Based Gene Transfer of Nonviral DNA Targeted to Murine Hepatocytes

    Directory of Open Access Journals (Sweden)

    Shingo Nakamura

    2013-01-01

    Full Text Available The liver is an important organ for supporting the life of an individual. Gene transfer toward this organ has been attempted in many laboratories to date; however, there have been few reports on improved liver-targeted gene delivery by using a nonviral vector. In this study, we examined the effect of various types of gene delivery carriers on enhancing the uptake and gene expression of exogenous DNA in murine hepatocytes when a hydrodynamics-based gene delivery (HGD is performed via tail-vein injection. Mice were singly injected with a large amount of phosphate-buffered saline containing reporter plasmid DNA and/or with a gene delivery carrier. One day after the gene delivery, the animals' livers were dissected and subjected to biochemical, histochemical, and molecular biological analyses. The strongest signal from the reporter plasmid DNA was observed when the DNA was mixed with a polyethylenimine- (PEI- based reagent. Coinjection with pCRTEIL (a loxP-floxed reporter construct and pTR/NCre (a liver-specific Cre expression vector resulted in the liver-specific recombination of pCRTEIL. The combination of PEI with HGD would thus be a valuable tool for liver-specific manipulation to examine the function of a gene of interest in the liver and for creating liver disease models.

  17. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis.

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim' based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks.

  18. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis

    Science.gov (United States)

    Zhou, Wei; Wen, Junhao; Koh, Yun Sing; Xiong, Qingyu; Gao, Min; Dobbie, Gillian; Alam, Shafiq

    2015-01-01

    Recommender systems are highly vulnerable to shilling attacks, both by individuals and groups. Attackers who introduce biased ratings in order to affect recommendations, have been shown to negatively affect collaborative filtering (CF) algorithms. Previous research focuses only on the differences between genuine profiles and attack profiles, ignoring the group characteristics in attack profiles. In this paper, we study the use of statistical metrics to detect rating patterns of attackers and group characteristics in attack profiles. Another question is that most existing detecting methods are model specific. Two metrics, Rating Deviation from Mean Agreement (RDMA) and Degree of Similarity with Top Neighbors (DegSim), are used for analyzing rating patterns between malicious profiles and genuine profiles in attack models. Building upon this, we also propose and evaluate a detection structure called RD-TIA for detecting shilling attacks in recommender systems using a statistical approach. In order to detect more complicated attack models, we propose a novel metric called DegSim’ based on DegSim. The experimental results show that our detection model based on target item analysis is an effective approach for detecting shilling attacks. PMID:26222882

  19. Compression of a Deep Competitive Network Based on Mutual Information for Underwater Acoustic Targets Recognition

    Directory of Open Access Journals (Sweden)

    Sheng Shen

    2018-04-01

    Full Text Available The accuracy of underwater acoustic targets recognition via limited ship radiated noise can be improved by a deep neural network trained with a large number of unlabeled samples. However, redundant features learned by deep neural network have negative effects on recognition accuracy and efficiency. A compressed deep competitive network is proposed to learn and extract features from ship radiated noise. The core idea of the algorithm includes: (1 Competitive learning: By integrating competitive learning into the restricted Boltzmann machine learning algorithm, the hidden units could share the weights in each predefined group; (2 Network pruning: The pruning based on mutual information is deployed to remove the redundant parameters and further compress the network. Experiments based on real ship radiated noise show that the network can increase recognition accuracy with fewer informative features. The compressed deep competitive network can achieve a classification accuracy of 89.1 % , which is 5.3 % higher than deep competitive network and 13.1 % higher than the state-of-the-art signal processing feature extraction methods.

  20. SU-E-J-220: Evaluation of Atlas-Based Auto-Segmentation (ABAS) in Head-And-Neck Adaptive Radiotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Liu, Q; Yan, D [William Beaumont Hospital, Royal Oak, MI (United States)

    2014-06-01

    Purpose: Evaluate the accuracy of atlas-based auto segmentation of organs at risk (OARs) on both helical CT (HCT) and cone beam CT (CBCT) images in head and neck (HN) cancer adaptive radiotherapy (ART). Methods: Six HN patients treated in the ART process were included in this study. For each patient, three images were selected: pretreatment planning CT (PreTx-HCT), in treatment CT for replanning (InTx-HCT) and a CBCT acquired in the same day of the InTx-HCT. Three clinical procedures of auto segmentation and deformable registration performed in the ART process were evaluated: a) auto segmentation on PreTx-HCT using multi-subject atlases, b) intra-patient propagation of OARs from PreTx-HCT to InTx-HCT using deformable HCT-to-HCT image registration, and c) intra-patient propagation of OARs from PreTx-HCT to CBCT using deformable CBCT-to-HCT image registration. Seven OARs (brainstem, cord, L/R parotid, L/R submandibular gland and mandible) were manually contoured on PreTx-HCT and InTx-HCT for comparison. In addition, manual contours on InTx-CT were copied on the same day CBCT, and a local region rigid body registration was performed accordingly for each individual OAR. For procedures a) and b), auto contours were compared to manual contours, and for c) auto contours were compared to those rigidly transferred contours on CBCT. Dice similarity coefficients (DSC) and mean surface distances of agreement (MSDA) were calculated for evaluation. Results: For procedure a), the mean DSC/MSDA of most OARs are >80%/±2mm. For intra-patient HCT-to-HCT propagation, the Resultimproved to >85%/±1.5mm. Compared to HCT-to-HCT, the mean DSC for HCT-to-CBCT propagation drops ∼2–3% and MSDA increases ∼0.2mm. This Resultindicates that the inferior imaging quality of CBCT seems only degrade auto propagation performance slightly. Conclusion: Auto segmentation and deformable propagation can generate OAR structures on HCT and CBCT images with clinically acceptable accuracy. Therefore

  1. SU-E-J-220: Evaluation of Atlas-Based Auto-Segmentation (ABAS) in Head-And-Neck Adaptive Radiotherapy

    International Nuclear Information System (INIS)

    Liu, Q; Yan, D

    2014-01-01

    Purpose: Evaluate the accuracy of atlas-based auto segmentation of organs at risk (OARs) on both helical CT (HCT) and cone beam CT (CBCT) images in head and neck (HN) cancer adaptive radiotherapy (ART). Methods: Six HN patients treated in the ART process were included in this study. For each patient, three images were selected: pretreatment planning CT (PreTx-HCT), in treatment CT for replanning (InTx-HCT) and a CBCT acquired in the same day of the InTx-HCT. Three clinical procedures of auto segmentation and deformable registration performed in the ART process were evaluated: a) auto segmentation on PreTx-HCT using multi-subject atlases, b) intra-patient propagation of OARs from PreTx-HCT to InTx-HCT using deformable HCT-to-HCT image registration, and c) intra-patient propagation of OARs from PreTx-HCT to CBCT using deformable CBCT-to-HCT image registration. Seven OARs (brainstem, cord, L/R parotid, L/R submandibular gland and mandible) were manually contoured on PreTx-HCT and InTx-HCT for comparison. In addition, manual contours on InTx-CT were copied on the same day CBCT, and a local region rigid body registration was performed accordingly for each individual OAR. For procedures a) and b), auto contours were compared to manual contours, and for c) auto contours were compared to those rigidly transferred contours on CBCT. Dice similarity coefficients (DSC) and mean surface distances of agreement (MSDA) were calculated for evaluation. Results: For procedure a), the mean DSC/MSDA of most OARs are >80%/±2mm. For intra-patient HCT-to-HCT propagation, the Resultimproved to >85%/±1.5mm. Compared to HCT-to-HCT, the mean DSC for HCT-to-CBCT propagation drops ∼2–3% and MSDA increases ∼0.2mm. This Resultindicates that the inferior imaging quality of CBCT seems only degrade auto propagation performance slightly. Conclusion: Auto segmentation and deformable propagation can generate OAR structures on HCT and CBCT images with clinically acceptable accuracy. Therefore

  2. A method for evaluating cognitively informed micro-targeted campaign strategies: An agent-based model proof of principle.

    Science.gov (United States)

    Madsen, Jens Koed; Pilditch, Toby D

    2018-01-01

    In political campaigns, perceived candidate credibility influences the persuasiveness of messages. In campaigns aiming to influence people's beliefs, micro-targeted campaigns (MTCs) that target specific voters using their psychological profile have become increasingly prevalent. It remains open how effective MTCs are, notably in comparison to population-targeted campaign strategies. Using an agent-based model, the paper applies recent insights from cognitive models of persuasion, extending them to the societal level in a novel framework for exploring political campaigning. The paper provides an initial treatment of the complex dynamics of population level political campaigning in a psychologically informed manner. Model simulations show that MTCs can take advantage of the psychology of the electorate by targeting voters favourable disposed towards the candidate. Relative to broad campaigning, MTCs allow for efficient and adaptive management of complex campaigns. Findings show that disliked MTC candidates can beat liked population-targeting candidates, pointing to societal questions concerning campaign regulations.

  3. Impact of Targeted Tuberculosis Vaccination Among a Mining Population in South Africa: A Model-Based Study.

    Science.gov (United States)

    Shrestha, Sourya; Chihota, Violet; White, Richard G; Grant, Alison D; Churchyard, Gavin J; Dowdy, David W

    2017-12-15

    Optimizing the use of new tools, such as vaccines, may play a crucial role in reaching global targets for tuberculosis (TB) control. Some of the most promising candidate vaccines target adults, although high-coverage mass vaccinations may be logistically more challenging among this population than among children. Vaccine-delivery strategies that target high-risk groups or settings might yield proportionally greater impact than do those that target the general population. We developed an individual-based TB transmission model representing a hypothetical population consisting of people who worked in South African gold mines or lived in associated labor-sending communities. We simulated the implementation of a postinfection adult vaccine with 60% efficacy and a mean effect duration of 10 years. We then compared the impact of a mine-targeted vaccination strategy, in which miners were vaccinated while in the mines, with that of a community-targeted strategy, in which random individuals within the labor-sending communities were vaccinated. Mine-targeted vaccination averted an estimated 0.37 TB cases per vaccine dose compared with 0.25 for community-targeted vaccination, for a relative efficacy of 1.46 (95% range, 1.13-1.91). The added benefit of mine-targeted vaccination primarily reflected the disproportionate demographic burden of TB among the population of adult males as a whole. As novel vaccines for TB are developed, venue-based vaccine delivery that targets high-risk demographic groups may improve both vaccine feasibility and the impact on transmission. © The Author(s) 2017. Published by Oxford University Press on behalf of the Johns Hopkins Bloomberg School of Public Health. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    International Nuclear Information System (INIS)

    Park, Ji-Ae; Lee, Yong Jin; Ko, In Ok; Kim, Tae-Jeong; Chang, Yongmin; Lim, Sang Moo; Kim, Kyeong Min; Kim, Jung Young

    2014-01-01

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images

  5. Improved tumor-targeting MRI contrast agents: Gd(DOTA) conjugates of a cycloalkane-based RGD peptide

    Energy Technology Data Exchange (ETDEWEB)

    Park, Ji-Ae, E-mail: jpark@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Lee, Yong Jin; Ko, In Ok [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Tae-Jeong; Chang, Yongmin [Institute of Biomedical Engineering, Kyungpook National University, Daegu (Korea, Republic of); Lim, Sang Moo [Department of Nuclear Medicine, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Kyeong Min [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Kim, Jung Young, E-mail: jykim@kirams.re.kr [Molecular Imaging Research Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

    2014-12-12

    Highlights: • Development of improved tumor-targeting MRI contrast agents. • To increase the targeting ability of RGD, we developed cycloalkane-based RGD peptides. • Gd(DOTA) conjugates of cycloalkane-based RGD peptide show improved tumor signal enhancement in vivo MR images. - Abstract: Two new MRI contrast agents, Gd-DOTA-c(RGD-ACP-K) (1) and Gd-DOTA-c(RGD-ACH-K) (2), which were designed by incorporating aminocyclopentane (ACP)- or aminocyclohexane (ACH)-carboxylic acid into Gd-DOTA (gadolinium-tetraazacyclo dodecanetetraacetic acid) and cyclic RGDK peptides, were synthesized and evaluated for tumor-targeting ability in vitro and in vivo. Binding affinity studies showed that both 1 and 2 exhibited higher affinity for integrin receptors than cyclic RGDyK peptides, which were used as a reference. These complexes showed high relaxivity and good stability in human serum and have the potential to improve target-specific signal enhancement in vivo MR images.

  6. Robust, fast and accurate vision-based localization of a cooperative target used for space robotic arm

    Science.gov (United States)

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

    2017-07-01

    When a space robotic arm deploys a payload, usually the pose between the cooperative target fixed on the payload and the hand-eye camera installed on the arm is calculated in real-time. A high-precision robust visual cooperative target localization method is proposed. Combing a circle, a line and dots as markers, a target that guarantees high detection rates is designed. Given an image, single-pixel-width smooth edges are drawn by a novel linking method. Circles are then quickly extracted using isophotes curvature. Around each circle, a square boundary in a pre-calculated proportion to the circle radius is set. In the boundary, the target is identified if certain numbers of lines exist. Based on the circle, the lines, and the target foreground and background intensities, markers are localized. Finally, the target pose is calculated by the Point-3-Perspective algorithm. The algorithm processes 8 frames per second with the target distance ranging from 0.3m to 1.5 m. It generated high-precision poses of above 97.5% on over 100,000 images regardless of camera background, target pose, illumination and motion blur. At 0.3 m, the rotation and translation errors were less than 0.015° and 0.2 mm. The proposed algorithm is very suitable for real-time visual measurement that requires high precision in aerospace.

  7. Directions for reactor target design based on the US heavy ion fusion systems assessment

    International Nuclear Information System (INIS)

    Wilson, D.C.; Dudziak, D.; Magelssen, G.; Zuckerman, D.; Dreimeyer, D.

    1986-01-01

    We studied areas of major uncertainty in target design using the cost of electricity as our figure of merit. Net electric power from the plant was fixed at 1000 MW to eliminate large effects due to economies of scale. The system is relatively insensitive to target gain. Factors of three changes in gain cause only 8 to 12% changes in electricity cost. An increase in the peak power needed to drive targets poses only a small cost risk, but requires many more beamlets be transported to the target. A shortening of the required ion range causes both cost and beamlet difficulties. A factor of 4 decrease in the required range at a fixed driver energy increases electricity cost by 44% and raises the number of beamlets to 240. Finally, the heavy ion fusion system can accommodate large increases in target costs. To address the major uncertainties, target design should concentrate on the understanding requirements for ion range and peak driver power

  8. Contrast agent based on nano-emulsion for targeted biomedical imaging

    International Nuclear Information System (INIS)

    Attia, Mohamed

    2016-01-01

    polymer poly(maleic anhydride-alt-1-octadecene) (PMAO). The in vitro results and in vivo evaluations were completely coherent approving that the neutral charged NPs are less toxic compared to the negatively charged ones that were highly up-taken in the cells causing stress to the cells and thereby affecting the toxicity. As a result they are different in biodistribution and pharmacokinetics. In this context, for the first time, we were able to functionalize the nano-emulsion droplets with ligand molecules by covalent bonds. Likewise we designed nano-droplets and coated by silica shell ended by amino groups and then followed by formation of amide bonds with grafting to dye ligand model (coumarin blue dye). The quantification of amino groups was performed by using spectroscopic and microscopic techniques, with a grafting efficiency as high as 41%. This process improves the targeting properties of such chemotherapeutic agents to the location of interest following active targeting mechanism (ligand receptor strategy). One of our achieved objectives was to engineer multifunctional polymer-based NPs encapsulating hydrophobic drug model as DDs and iron oxide NPs as a theranostic model. To conclude, novel contrast agents and delivering systems were synthesized with outstanding physicochemical characteristics and suitable for in vivo medium with high efficacy and low toxicity [fr

  9. A RNA-DNA Hybrid Aptamer for Nanoparticle-Based Prostate Tumor Targeted Drug Delivery

    Directory of Open Access Journals (Sweden)

    John C. Leach

    2016-03-01

    Full Text Available The side effects of radio- and chemo-therapy pose long-term challenges on a cancer patient’s health. It is, therefore, highly desirable to develop more effective therapies that can specifically target carcinoma cells without damaging normal and healthy cells. Tremendous efforts have been made in the past to develop targeted drug delivery systems for solid cancer treatment. In this study, a new aptamer, A10-3-J1, which recognizes the extracellular domain of the prostate specific membrane antigen (PSMA, was designed. A super paramagnetic iron oxide nanoparticle-aptamer-doxorubicin (SPIO-Apt-Dox was fabricated and employed as a targeted drug delivery platform for cancer therapy. This DNA RNA hybridized aptamer antitumor agent was able to enhance the cytotoxicity of targeted cells while minimizing collateral damage to non-targeted cells. This SPIO-Apt-Dox nanoparticle has specificity to PSMA+ prostate cancer cells. Aptamer inhibited nonspecific uptake of membrane-permeable doxorubic to the non-target cells, leading to reduced untargeted cytotoxicity and endocytic uptake while enhancing targeted cytotoxicity and endocytic uptake. The experimental results indicate that the drug delivery platform can yield statistically significant effectiveness being more cytotoxic to the targeted cells as opposed to the non-targeted cells.

  10. An Improved Algorithm to Delineate Urban Targets with Model-Based Decomposition of PolSAR Data

    Directory of Open Access Journals (Sweden)

    Dingfeng Duan

    2017-10-01

    Full Text Available In model-based decomposition algorithms using polarimetric synthetic aperture radar (PolSAR data, urban targets are typically identified based on the existence of strong double-bounced scattering. However, urban targets with large azimuth orientation angles (AOAs produce strong volumetric scattering that appears similar to scattering characteristics from tree canopies. Due to scattering ambiguity, urban targets can be classified into the vegetation category if the same classification scheme of the model-based PolSAR decomposition algorithms is followed. To resolve the ambiguity and to reduce the misclassification eventually, we introduced a correlation coefficient that characterized scattering mechanisms of urban targets with variable AOAs. Then, an existing volumetric scattering model was modified, and a PolSAR decomposition algorithm developed. The validity and effectiveness of the algorithm were examined using four PolSAR datasets. The algorithm was valid and effective to delineate urban targets with a wide range of AOAs, and applicable to a broad range of ground targets from urban areas, and from upland and flooded forest stands.

  11. DNA Targeting Sequence Improves Magnetic Nanoparticle-Based Plasmid DNA Transfection Efficiency in Model Neurons.

    Science.gov (United States)

    Vernon, Matthew M; Dean, David A; Dobson, Jon

    2015-08-17

    Efficient non-viral plasmid DNA transfection of most stem cells, progenitor cells and primary cell lines currently presents an obstacle for many applications within gene therapy research. From a standpoint of efficiency and cell viability, magnetic nanoparticle-based DNA transfection is a promising gene vectoring technique because it has demonstrated rapid and improved transfection outcomes when compared to alternative non-viral methods. Recently, our research group introduced oscillating magnet arrays that resulted in further improvements to this novel plasmid DNA (pDNA) vectoring technology. Continued improvements to nanomagnetic transfection techniques have focused primarily on magnetic nanoparticle (MNP) functionalization and transfection parameter optimization: cell confluence, growth media, serum starvation, magnet oscillation parameters, etc. Noting that none of these parameters can assist in the nuclear translocation of delivered pDNA following MNP-pDNA complex dissociation in the cell's cytoplasm, inclusion of a cassette feature for pDNA nuclear translocation is theoretically justified. In this study incorporation of a DNA targeting sequence (DTS) feature in the transfecting plasmid improved transfection efficiency in model neurons, presumably from increased nuclear translocation. This observation became most apparent when comparing the response of the dividing SH-SY5Y precursor cell to the non-dividing and differentiated SH-SY5Y neuroblastoma cells.

  12. Targeting Sindbis virus-based vectors to Fc receptor-positive cell types

    International Nuclear Information System (INIS)

    Klimstra, William B.; Williams, Jacqueline C.; Ryman, Kate D.; Heidner, Hans W.

    2005-01-01

    Some viruses display enhanced infection for Fc receptor (FcR)-positive cell types when complexed with virus-specific immunoglobulin (Ig). This process has been termed antibody-dependent enhancement of viral infection (ADE). We reasoned that the mechanism of ADE could be exploited and adapted to target alphavirus-based vectors to FcR-positive cell types. Towards this goal, recombinant Sindbis viruses were constructed that express 1 to 4 immunoglobulin-binding domains of protein L (PpL) as N-terminal extensions of the E2 glycoprotein. PpL is a bacterial protein that binds the variable region of antibody kappa light chains from a range of mammalian species. The recombinant viruses incorporated PpL/E2 fusion proteins into the virion structure and recapitulated the species-specific Ig-binding phenotypes of native PpL. Virions reacted with non-immune serum or purified IgG displayed enhanced binding and ADE for several species-matched FcR-positive murine and human cell lines. ADE required virus expression of a functional PpL Ig-binding domain, and appeared to be FcγR-mediated. Specifically, ADE did not occur with FcγR-negative cells, did not require active complement proteins, and did not occur on FcγR-positive murine cell lines when virions were bound by murine IgG-derived F(ab') 2 fragments

  13. Pilot evaluation of a web-based intervention targeting sexual health service access.

    Science.gov (United States)

    Brown, K E; Newby, K; Caley, M; Danahay, A; Kehal, I

    2016-04-01

    Sexual health service access is fundamental to good sexual health, yet interventions designed to address this have rarely been implemented or evaluated. In this article, pilot evaluation findings for a targeted public health behavior change intervention, delivered via a website and web-app, aiming to increase uptake of sexual health services among 13-19-year olds are reported. A pre-post questionnaire-based design was used. Matched baseline and follow-up data were identified from 148 respondents aged 13-18 years. Outcome measures were self-reported service access, self-reported intention to access services and beliefs about services and service access identified through needs analysis. Objective service access data provided by local sexual health services were also analyzed. Analysis suggests the intervention had a significant positive effect on psychological barriers to and antecedents of service access among females. Males, who reported greater confidence in service access compared with females, significantly increased service access by time 2 follow-up. Available objective service access data support the assertion that the intervention may have led to increases in service access. There is real promise for this novel digital intervention. Further evaluation is planned as the model is licensed to and rolled out by other local authorities in the United Kingdom. © The Author 2016. Published by Oxford University Press. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  14. Live-cell CLEM of subcellular targets: an optimized procedure for polymer-based imaging substrates.

    Science.gov (United States)

    Padman, Benjamin S; Ramm, Georg

    2014-01-01

    Live-cell correlative light and electron microscopy permits the visualization of ultrastructure details associated with dynamic biological processes. On the optical level, fluorescence microscopy can be further combined with functional studies of intracellular processes and manipulation of biological samples using laser light. However, the major challenge is to relocate intracellular compartments in three dimensions after the sample has undergone an extensive EM sample preparation process. Here, we describe a detailed protocol for live-cell CLEM that provides easy guidance for 3D relocalization. Based on the use of the novel polymer film TOPAS as direct imaging substrate, we provide a setup that uses highly visible toner particles for tracking the region of interest in 2D and fiducial markers for the 3D relocation of intracellular structures. An example is given where a single mitochondria is targeted by laser microirradiation in live-cell fluorescence microscopy. After relocating the same structure in 3D in serial EM sections, the changes to the mitochondrial ultrastructure are observed by TEM. The method is suitable for correlation of live-cell microscopy of cells and can be performed using any inverted optical microscope. © 2014 Elsevier Inc. All rights reserved.

  15. Photodynamic quenched cathepsin activity based probes for cancer detection and macrophage targeted therapy.

    Science.gov (United States)

    Ben-Nun, Yael; Merquiol, Emmanuelle; Brandis, Alexander; Turk, Boris; Scherz, Avigdor; Blum, Galia

    2015-01-01

    Elevated cathepsins levels and activities are found in several types of human cancer, making them valuable biomarkers for detection and targeting therapeutics. We designed small molecule quenched activity-based probes (qABPs) that fluoresce upon activity-dependent covalent modification, yielding cell killing by Photodynamic Therapy (PDT). These novel molecules are highly selective theranostic probes that enable both detection and treatment of cancer with minimal side effects. Our qABPs carry a photosensitizer (PS), which is activated by light, resulting in oxidative stress and subsequent cell ablation, and a quencher that when removed by active cathepsins allow the PS to fluoresce and demonstrate PD properties. Our most powerful and stable PS-qABP, YBN14, consists of a selective cathepsin recognition sequence, a QC-1 quencher and a new bacteriochlorin derivative as a PS. YBN14 allowed rapid and selective non-invasive in vivo imaging of subcutaneous tumors and induced specific tumor macrophage apoptosis by light treatment, resulting in a substantial tumor shrinkage in an aggressive breast cancer mouse model. These results demonstrate for the first time that the PS-qABPs technology offers a functional theranostic tool, which can be applied to numerous tumor types and other inflammation-associated diseases.

  16. Reversal of multidrug resistance by mitochondrial targeted self-assembled nanocarrier based on stearylamine.

    Science.gov (United States)

    Zhang, Zhiwen; Liu, Zeying; Ma, Li; Jiang, Shijun; Wang, Yixin; Yu, Haijun; Yin, Qi; Cui, Jingbin; Li, Yaping

    2013-06-03

    Multidrug resistance (MDR) remains one of the major challenges for successful chemotherapy. Herein, we tried to develope a mitochondria targeted teniposide loaded self-assembled nanocarrier based on stearylamine (SA-TSN) to reverse MDR of breast cancer. SA-TSN was nanometer-sized spherical particles (31.59 ± 3.43 nm) with a high encapsulation efficiency (99.25 ± 0.21%). The MDR in MCF-7/ADR cells was obviously reduced by SA-TSN, which mainly attributed to the markedly reduced expression of P-gp, increased percentages in G2 phase, selectively accumulation in mitochondria, decrease of mitochondrial membrane potential, and greatly improved apoptosis. The plasma concentration of teniposide was greatly improved by SA-TSN, and the intravenously administered SA-TSN could accumulate in the tumor site and penetrate into the inner site of tumor in MCF-7/ADR induced xenografts. In particular, the in vivo tumor inhibitory efficacy of SA-TSN in MCF-7/ADR induced models was more effective than that of teniposide loaded self-assembled nanocarrier without stearylamine (TSN) and teniposide solution (TS), which verified the effectiveness of SA-TSN in reversal of MDR. Thereby, SA-TSN has potential to circumvent the MDR for the chemotherapy of breast cancer.

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

    Directory of Open Access Journals (Sweden)

    Johannes Krisam

    2015-05-01

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

  18. Cryogenic Hydrogen Fuel for Controlled Inertial Confinement Fusion (Cryogenic Target Factory Concept Based on FST-Layering Method)

    Science.gov (United States)

    Aleksandrova, I. V.; Koresheva, E. R.; Koshelev, I. E.; Krokhin, O. N.; Nikitenko, A. I.; Osipov, I. E.

    2017-12-01

    A central element of a power plant based on inertial confinement fusion (ICF) is a target with cryogenic hydrogen fuel that should be delivered to the center of a reactor chamber with a high accuracy and repetition rate. Therefore, a cryogenic target factory (CTF) is an integral part of any ICF reactor. A promising way to solve this problem consists in the FST layering method developed at the Lebedev Physical Institute (LPI). This method (rapid fuel layering inside moving free-standing targets) is unique, having no analogs in the world. The further development of FST-layering technologies is implemented in the scope of the LPI program for the creation of a modular CTF and commercialization of the obtained results. In this report, we discuss our concept of CTF (CTF-LPI) that exhibits the following distinctive features: using a FST-layering technology for the elaboration of an in-line production of cryogenic targets, using an effect of quantum levitation of high-temperature superconductors (HTSCs) in magnetic field for noncontacting manipulation, transport, and positioning of the free-standing cryogenic targets, as well as in using a Fourier holography technique for an on-line characterization and tracking of the targets flying into the reactor chamber. The results of original experimental and theoretical investigations performed at LPI indicate that the existing and developing target fabrication capabilities and technologies can be applied to ICF target production. The unique scientific, engineering, and technological base developed in Russia at LPI allows one to make a CTFLPI prototype for mass production of targets and delivery thereof at the required velocity into the ICF reactor chamber.

  19. The Implementation of Targeted Temperature Management: An Evidence-Based Guideline from the Neurocritical Care Society.

    Science.gov (United States)

    Madden, Lori Kennedy; Hill, Michelle; May, Teresa L; Human, Theresa; Guanci, Mary McKenna; Jacobi, Judith; Moreda, Melissa V; Badjatia, Neeraj

    2017-12-01

    Targeted temperature management (TTM) is often used in neurocritical care to minimize secondary neurologic injury and improve outcomes. TTM encompasses therapeutic hypothermia, controlled normothermia, and treatment of fever. TTM is best supported by evidence from neonatal hypoxic-ischemic encephalopathy and out-of-hospital cardiac arrest, although it has also been explored in ischemic stroke, traumatic brain injury, and intracranial hemorrhage patients. Critical care clinicians using TTM must select appropriate cooling techniques, provide a reasonable rate of cooling, manage shivering, and ensure adequate patient monitoring among other challenges. The Neurocritical Care Society recruited experts in neurocritical care, nursing, and pharmacotherapy to form a writing Committee in 2015. The group generated a set of 16 clinical questions relevant to TTM using the PICO format. With the assistance of a research librarian, the Committee undertook a comprehensive literature search with no back date through November 2016 with additional references up to March 2017. The Committee utilized GRADE methodology to adjudicate the quality of evidence as high, moderate, low, or very low based on their confidence that the estimate of effect approximated the true effect. They generated recommendations regarding the implementation of TTM based on this systematic review only after considering the quality of evidence, relative risks and benefits, patient values and preferences, and resource allocation. This guideline is intended for neurocritical care clinicians who have chosen to use TTM in patient care; it is not meant to provide guidance regarding the clinical indications for TTM itself. While there are areas of TTM practice where clear evidence guides strong recommendations, many of the recommendations are conditional, and must be contextualized to individual patient and system needs.

  20. Track extraction of moving targets in astronomical images based on the algorithm of NCST-PCNN

    Science.gov (United States)

    Du, Lin; Sun, Huayan; Zhang, Tinghua; Xu, Taohu

    2015-10-01

    Space targets in astronomical images such as spacecraft and space debris are always in the low level of brightness and hold a small amount of pixels, which are difficult to distinguish from fixed stars. Because of the difficulties of space target information extraction, dynamic object monitoring plays an important role in the military, aerospace and other fields, track extraction of moving targets in short-exposure astronomical images holds great significance. Firstly, capture the interesting stars by region growing method in the sequence of short-exposure images and extract the barycenter of interesting star by gray weighted method. Secondly, use adaptive threshold method to remove the error matching points and register the sequence of astronomical images. Thirdly, fuse the registered images by NCST-PCNN image fusion algorithm to hold the energy of stars in the images. Fourthly, get the difference of fused star image and final star image by subtraction of brightness value in the two images, the interesting possible moving targets will be captured by energy accumulation method. Finally, the track of moving target in astronomical images will be extracted by judging the accuracy of moving targets by track association and excluding the false moving targets. The algorithm proposed in the paper can effectively extract the moving target which is added artificially from three images or four images respectively, which verifies the effectiveness of the algorithm.

  1. Accelerator-based neutron source using a cold deuterium target with degenerate electrons

    Directory of Open Access Journals (Sweden)

    R. E. Phillips

    2013-07-01

    Full Text Available A neutron generator is considered in which a beam of tritons is incident on a hypothetical cold deuterium target with degenerate electrons. The energy efficiency of neutron generation is found to increase substantially with electron density. Recent reports of potential targets are discussed.

  2. Introduction to the special issue: GIS-based mineral potential targeting

    Science.gov (United States)

    Yousefi, Mahyar; Nykänen, Vesa

    2017-04-01

    Mineral potential targeting using geographical information system is an efficient technique to delimit a study area for further exploration of mineral deposits. This introduction presents an overview of the mineral potential modeling methods and future perspectives of research in the fields of target generation and summarizes the papers that have been incorporated into this Special Issue of the Journal of African Earth Sciences.

  3. Micro-Doppler Feature Extraction and Recognition Based on Netted Radar for Ballistic Targets

    Directory of Open Access Journals (Sweden)

    Feng Cun-qian

    2015-12-01

    Full Text Available This study examines the complexities of using netted radar to recognize and resolve ballistic midcourse targets. The application of micro-motion feature extraction to ballistic mid-course targets is analyzed, and the current status of application and research on micro-motion feature recognition is concluded for singlefunction radar networks such as low- and high-resolution imaging radar networks. Advantages and disadvantages of these networks are discussed with respect to target recognition. Hybrid-mode radar networks combine low- and high-resolution imaging radar and provide a specific reference frequency that is the basis for ballistic target recognition. Main research trends are discussed for hybrid-mode networks that apply micromotion feature extraction to ballistic mid-course targets.

  4. Peptide Based Targeted Therapeutic Radiopharmaceuticals: A Focus on the Synthesis of Radiolabelled Nanobodies

    International Nuclear Information System (INIS)

    Impens, N.; Campsteyn, A.; Aerts, A.; Baatout, S.; Devoogdt, N.; Caveliers, V.; Xavier, C.; Lahoutte, T.

    2009-01-01

    In 1993, the Vrije Universiteit Brussel (Brussels, Belgium) discovered in the blood of camelidae antibodies consisting of only a heavy chain. Due to the lack of the light chain only the variable part of the heavy chain is important for antigen binding. This variable part of these heavy-chain-only antibodies is a good candidate as a targeted therapeutic radiopharmaceutical and was called a nanobody, having a molecular weight of about 15 kDa. Its dimensions are included in between the small peptides like derived from e.g. somatostatin, and the classical monoclonal antibodies. This makes that some characteristics like the physical behaviour, the chemical stability, the penetration in tumour and in healthy tissues, and the blood clearance lie in between the characteristics of the small peptides and the monoclonal antibodies, therefore taking advantage of both extremes. Nanobodies have been humanised to decrease the immunogenic response. The building blocks of molecules such as the octreotide, nanobodies and monoclonal antibodies are amino acids linked via peptide bonds. The modification reactions are therefore all based on the same 'peptide chemistry'. The functional groups on the present amino acids will determine the possible reactions. In order to link a radionuclide to the nanobodies, we opted to use bifunctional ligands containing DOTA, because this is a suitable chelating agent for the diagnostic radionuclide Ga-68, and for therapeutic radionuclides such as Lu-177 and Y-90, covering short and long range β-particle emitters suitable for attacking a wide range of tumour sizes. The ratio of bifunctional ligand to nanobody can be varied by carefully selecting the functional groups of the peptide involved in the reaction with the bifunctional ligand, avoiding the complementarity determining region (CDR), i.e. the part of the molecule binding to the antigen. This is a first way to predetermine the amount of radionuclides that can be linked to the peptide, or the

  5. Targeting miRNA-based medicines to cystic fibrosis airway epithelial cells using nanotechnology

    Directory of Open Access Journals (Sweden)

    McKiernan PJ

    2013-10-01

    Full Text Available Paul J McKiernan,2 Orla Cunninghamm,1,2 Catherine M Greenem,2 Sally-Ann Cryan1,31School of Pharmacy, Royal College of Surgeons in Ireland, 2Respiratory Research Division, Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, 3Trinity Centre for Bioengineering, Trinity College Dublin, Dublin, IrelandAbstract: Cystic fibrosis (CF is an inherited disorder characterized by chronic airway inflammation. microRNAs (miRNAs are endogenous small RNAs which act on messenger (mRNA at a post transcriptional level, and there is a growing understanding that altered expression of miRNA is involved in the CF phenotype. Modulation of miRNA by replacement using miRNA mimics (premiRs presents a new therapeutic paradigm for CF, but effective and safe methods of delivery to the CF epithelium are limiting clinical translation. Herein, polymeric nanoparticles are investigated for delivery of miRNA mimics into CF airway epithelial cells, using miR-126 as a proof-of-concept premiR cargo to determine efficiency. Two polymers, polyethyleneimine (PEI and chitosan, were used to prepare miRNA nanomedicines, characterized for their size, surface (zeta potential, and RNA complexation efficiency, and screened for delivery and cytotoxicity in CFBE41o- (human F508del cystic fibrosis transmembrane conductance regulator bronchial epithelial cells using a novel high content analysis method. RNA extraction was carried out 24 hours post transfection, and miR-126 and TOM1 (target of Myb1 expression (a validated miR-126 target was assessed. Manufacture was optimized to produce small nanoparticles that effectively complexed miRNA. Using high content analysis, PEI-based nanoparticles were more effective than chitosan-based nanoparticles in facilitating uptake of miRNA into CFBE41o- cells and this was confirmed in miR-126 assays. PEI-premiR-126 nanoparticles at low nitrogen/phosphate (N/P ratios resulted in significant knockdown of

  6. An integrated structure- and system-based framework to identify new targets of metabolites and known drugs

    KAUST Repository

    Naveed, Hammad

    2015-08-18

    Motivation: The inherent promiscuity of small molecules towards protein targets impedes our understanding of healthy versus diseased metabolism. This promiscuity also poses a challenge for the pharmaceutical industry as identifying all protein targets is important to assess (side) effects and repositioning opportunities for a drug. Results: Here, we present a novel integrated structure- and system-based approach of drug-target prediction (iDTP) to enable the large-scale discovery of new targets for small molecules, such as pharmaceutical drugs, co-factors and metabolites (collectively called ‘drugs’). For a given drug, our method uses sequence order–independent structure alignment, hierarchical clustering, and probabilistic sequence similarity to construct a probabilistic pocket ensemble (PPE) that captures promiscuous structural features of different binding sites on known targets. A drug’s PPE is combined with an approximation of its delivery profile to reduce false positives. In our cross-validation study, we use iDTP to predict the known targets of eleven drugs, with 63% sensitivity and 81% specificity. We then predicted novel targets for these drugs—two that are of high pharmacological interest, the nuclear receptor PPARγ and the oncogene Bcl-2, were successfully validated through in vitro binding experiments. Our method is broadly applicable for the prediction of protein-small molecule interactions with several novel applications to biological research and drug development.

  7. Targeting c-kit receptor in neuroblastomas and colorectal cancers using stem cell factor (SCF)-based recombinant bacterial toxins.

    Science.gov (United States)

    Choudhary, Swati; Pardo, Alessa; Rosinke, Reinhard; Batra, Janendra K; Barth, Stefan; Verma, Rama S

    2016-01-01

    Autocrine activation of c-kit (KIT receptor tyrosine kinase) has been postulated to be a potent oncogenic driver in small cell lung cancer, neuroblastoma (NB), and poorly differentiated colorectal carcinoma (CRC). Although targeted therapy involving tyrosine kinase inhibitors (TKIs) such as imatinib mesylate is highly effective for gastrointestinal stromal tumor carrying V560G c-kit mutation, it does not show much potential for targeting wild-type KIT (WT-KIT). Our study demonstrates the role of stem cell factor (SCF)-based toxin conjugates for targeting WT-KIT-overexpressing malignancies such as NBs and CRCs. We constructed SCF-based recombinant bacterial toxins by genetically fusing mutated form of natural ligand SCF to receptor binding deficient forms of Diphtheria toxin (DT) or Pseudomonas exotoxin A (ETA') and evaluated their efficacy in vitro. Efficient targeting was achieved in all receptor-positive neuroblastoma (IMR-32 and SHSY5Y) and colon cancer cell lines (COLO 320DM, HCT 116, and DLD-1) but not in receptor-negative breast carcinoma cell line (MCF-7) thereby proving specificity. While dose- and time-dependent cytotoxicity was observed in both neuroblastoma cell lines, COLO 320DM and HCT 116 cells, only an anti-proliferative effect was observed in DLD-1 cells. We prove that these novel targeting agents have promising potential as KIT receptor tyrosine kinase targeting system.

  8. Characterizing and optimizing human anticancer drug targets based on topological properties in the context of biological pathways.

    Science.gov (United States)

    Zhang, Jian; Wang, Yan; Shang, Desi; Yu, Fulong; Liu, Wei; Zhang, Yan; Feng, Chenchen; Wang, Qiuyu; Xu, Yanjun; Liu, Yuejuan; Bai, Xuefeng; Li, Xuecang; Li, Chunquan

    2015-04-01

    One of the challenging problems in drug discovery is to identify the novel targets for drugs. Most of the traditional methods for drug targets optimization focused on identifying the particular families of "druggable targets", but ignored their topological properties based on the biological pathways. In this study, we characterized the topological properties of human anticancer drug targets (ADTs) in the context of biological pathways. We found that the ADTs tended to present the following seven topological properties: influence the number of the pathways related to cancer, be localized at the start or end of the pathways, interact with cancer related genes, exhibit higher connectivity, vulnerability, betweenness, and closeness than other genes. We first ranked ADTs based on their topological property values respectively, then fused them into one global-rank using the joint cumulative distribution of an N-dimensional order statistic to optimize human ADTs. We applied the optimization method to 13 anticancer drugs, respectively. Results demonstrated that over 70% of known ADTs were ranked in the top 20%. Furthermore, the performance for mercaptopurine was significant: 6 known targets (ADSL, GMPR2, GMPR, HPRT1, AMPD3, AMPD2) were ranked in the top 15 and other four out of the top 15 (MAT2A, CDKN1A, AREG, JUN) have the potentialities to become new targets for cancer therapy. Copyright © 2015 Elsevier Inc. All rights reserved.

  9. Mitochondria-Targeted Triphenylphosphonium-Based Compounds: Syntheses, Mechanisms of Action, and Therapeutic and Diagnostic Applications.

    Science.gov (United States)

    Zielonka, Jacek; Joseph, Joy; Sikora, Adam; Hardy, Micael; Ouari, Olivier; Vasquez-Vivar, Jeannette; Cheng, Gang; Lopez, Marcos; Kalyanaraman, Balaraman

    2017-08-09

    Mitochondria are recognized as one of the most important targets for new drug design in cancer, cardiovascular, and neurological diseases. Currently, the most effective way to deliver drugs specifically to mitochondria is by covalent linking a lipophilic cation such as an alkyltriphenylphosphonium moiety to a pharmacophore of interest. Other delocalized lipophilic cations, such as rhodamine, natural and synthetic mitochondria-targeting peptides, and nanoparticle vehicles, have also been used for mitochondrial delivery of small molecules. Depending on the approach used, and the cell and mitochondrial membrane potentials, more than 1000-fold higher mitochondrial concentration can be achieved. Mitochondrial targeting has been developed to study mitochondrial physiology and dysfunction and the interaction between mitochondria and other subcellular organelles and for treatment of a variety of diseases such as neurodegeneration and cancer. In this Review, we discuss efforts to target small-molecule compounds to mitochondria for probing mitochondria function, as diagnostic tools and potential therapeutics. We describe the physicochemical basis for mitochondrial accumulation of lipophilic cations, synthetic chemistry strategies to target compounds to mitochondria, mitochondrial probes, and sensors, and examples of mitochondrial targeting of bioactive compounds. Finally, we review published attempts to apply mitochondria-targeted agents for the treatment of cancer and neurodegenerative diseases.

  10. Dim small targets detection based on self-adaptive caliber temporal-spatial filtering

    Science.gov (United States)

    Fan, Xiangsuo; Xu, Zhiyong; Zhang, Jianlin; Huang, Yongmei; Peng, Zhenming

    2017-09-01

    To boost the detect ability of dim small targets, this paper began by using improved anisotropy for background prediction (IABP), followed by target enhancement by improved high-order cumulates (HQS). Finally, on the basis of image pre-processing, to address the problem of missed and wrong detection caused by fixed caliber of traditional pipeline filtering, this paper used targets' multi-frame movement correlation in the time-space domain, combined with the scale-space theory, to propose a temporal-spatial filtering algorithm which allows the caliber to make self-adaptive changes according to the changes of the targets' scale, effectively solving the detection-related issues brought by unchanged caliber and decreased/increased size of the targets. Experiments showed that the improved anisotropic background predication could be loyal to the true background of the original image to the maximum extent, presenting a superior overall performance to other background prediction methods; the improved HQS significantly increased the signal-noise ratio of images; when the signal-noise ratio was lower than 2.6 dB, this detection algorithm could effectively eliminate noise and detect targets. For the algorithm, the lowest signal-to-noise ratio of the detectable target is 0.37.

  11. A comparison of gantry-mounted x-ray-based real-time target tracking methods.

    Science.gov (United States)

    Montanaro, Tim; Nguyen, Doan Trang; Keall, Paul J; Booth, Jeremy; Caillet, Vincent; Eade, Thomas; Haddad, Carol; Shieh, Chun-Chien

    2018-03-01

    -posterior direction. Inferred traces often exhibit higher interdimensional correlation, which are not true representation of thoracic/abdominal motion and may underestimate kV-based tracking errors. The use of internal traces acquired from systems such as Calypso is advised for future kV-based tracking studies. The Gaussian PDF method is the most accurate 2D-3D inference method for tracking thoracic/abdominal targets. Motion magnitude has significant impact on 2D-3D inference error, and should be considered when estimating kV-based tracking error. © 2018 American Association of Physicists in Medicine.

  12. Fragment-Based Screening of a Natural Product Library against 62 Potential Malaria Drug Targets Employing Native Mass Spectrometry.

    Science.gov (United States)

    Vu, Hoan; Pedro, Liliana; Mak, Tin; McCormick, Brendan; Rowley, Jessica; Liu, Miaomiao; Di Capua, Angela; Williams-Noonan, Billy; Pham, Ngoc B; Pouwer, Rebecca; Nguyen, Bao; Andrews, Katherine T; Skinner-Adams, Tina; Kim, Jessica; Hol, Wim G J; Hui, Raymond; Crowther, Gregory J; Van Voorhis, Wesley C; Quinn, Ronald J

    2018-03-03

    Natural products are well known for their biological relevance, high degree of three-dimensionality, and access to areas of largely unexplored chemical space. To shape our understanding of the interaction between natural products and protein targets in the postgenomic era, we have used native mass spectrometry to investigate 62 potential protein targets for malaria using a natural-product-based fragment library. We reveal here 96 low-molecular-weight natural products identified as binding partners of 32 of the putative malarial targets. Seventy-nine (79) fragments have direct growth inhibition on Plasmodium falciparum at concentrations that are promising for the development of fragment hits against these protein targets. This adds a fragment library to the published HTS active libraries in the public domain.

  13. Inferring multi-target QSAR models with taxonomy-based multi-task learning.

    Science.gov (United States)

    Rosenbaum, Lars; Dörr, Alexander; Bauer, Matthias R; Boeckler, Frank M; Zell, Andreas

    2013-07-11

    A plethora of studies indicate that the development of multi-target drugs is beneficial for complex diseases like cancer. Accurate QSAR models for each of the desired targets assist the optimization of a lead candidate by the prediction of affinity profiles. Often, the targets of a multi-target drug are sufficiently similar such that, in principle, knowledge can be transferred between the QSAR models to improve the model accuracy. In this study, we present two different multi-task algorithms from the field of transfer learning that can exploit the similarity between several targets to transfer knowledge between the target specific QSAR models. We evaluated the two methods on simulated data and a data set of 112 human kinases assembled from the public database ChEMBL. The relatedness between the kinase targets was derived from the taxonomy of the humane kinome. The experiments show that multi-task learning increases the performance compared to training separate models on both types of data given a sufficient similarity between the tasks. On the kinase data, the best multi-task approach improved the mean squared error of the QSAR models of 58 kinase targets. Multi-task learning is a valuable approach for inferring multi-target QSAR models for lead optimization. The application of multi-task learning is most beneficial if knowledge can be transferred from a similar task with a lot of in-domain knowledge to a task with little in-domain knowledge. Furthermore, the benefit increases with a decreasing overlap between the chemical space spanned by the tasks.

  14. HuMiTar: A sequence-based method for prediction of human microRNA targets

    Directory of Open Access Journals (Sweden)

    Chen Ke

    2008-12-01

    Full Text Available Abstract Background MicroRNAs (miRs are small noncoding RNAs that bind to complementary/partially complementary sites in the 3' untranslated regions of target genes to regulate protein production of the target transcript and to induce mRNA degradation or mRNA cleavage. The ability to perform accurate, high-throughput identification of physiologically active miR targets would enable functional characterization of individual miRs. Current target prediction methods include traditional approaches that are based on specific base-pairing rules in the miR's seed region and implementation of cross-species conservation of the target site, and machine learning (ML methods that explore patterns that contrast true and false miR-mRNA duplexes. However, in the case of the traditional methods research shows that some seed region matches that are conserved are false positives and that some of the experimentally validated target sites are not conserved. Results We present HuMiTar, a computational method for identifying common targets of miRs, which is based on a scoring function that considers base-pairing for both seed and non-seed positions for human miR-mRNA duplexes. Our design shows that certain non-seed miR nucleotides, such as 14, 18, 13, 11, and 17, are characterized by a strong bias towards formation of Watson-Crick pairing. We contrasted HuMiTar with several representative competing methods on two sets of human miR targets and a set of ten glioblastoma oncogenes. Comparison with the two best performing traditional methods, PicTar and TargetScanS, and a representative ML method that considers the non-seed positions, NBmiRTar, shows that HuMiTar predictions include majority of the predictions of the other three methods. At the same time, the proposed method is also capable of finding more true positive targets as a trade-off for an increased number of predictions. Genome-wide predictions show that the proposed method is characterized by 1.99 signal

  15. Systematic Identification and Assessment of Therapeutic Targets for Breast Cancer Based on Genome-Wide RNA Interference Transcriptomes

    Directory of Open Access Journals (Sweden)

    Yang Liu

    2017-02-01

    Full Text Available With accumulating public omics data, great efforts have been made to characterize the genetic heterogeneity of breast cancer. However, identifying novel targets and selecting the best from the sizeable lists of candidate targets is still a key challenge for targeted therapy, largely owing to the lack of economical, efficient and systematic discovery and assessment to prioritize potential therapeutic targets. Here, we describe an approach that combines the computational evaluation and objective, multifaceted assessment to systematically identify and prioritize targets for biological validation and therapeutic exploration. We first establish the reference gene expression profiles from breast cancer cell line MCF7 upon genome-wide RNA interference (RNAi of a total of 3689 genes, and the breast cancer query signatures using RNA-seq data generated from tissue samples of clinical breast cancer patients in the Cancer Genome Atlas (TCGA. Based on gene set enrichment analysis, we identified a set of 510 genes that when knocked down could significantly reverse the transcriptome of breast cancer state. We then perform multifaceted assessment to analyze the gene set to prioritize potential targets for gene therapy. We also propose drug repurposing opportunities and identify potentially druggable proteins that have been poorly explored with regard to the discovery of small-molecule modulators. Finally, we obtained a small list of candidate therapeutic targets for four major breast cancer subtypes, i.e., luminal A, luminal B, HER2+ and triple negative breast cancer. This RNAi transcriptome-based approach can be a helpful paradigm for relevant researches to identify and prioritize candidate targets for experimental validation.

  16. Hyaluronic acid based self-assembling nanosystems for CD44 target mediated siRNA delivery to solid tumors

    Science.gov (United States)

    Ganesh, Shanthi; Iyer, Arun K.; Morrissey, David V.; Amiji, Mansoor M.

    2013-01-01

    Anticancer therapeutics employing RNA interference mechanism holds promising potentials for sequence-specific silencing of target genes. However targeted delivery of siRNAs to tumor tissues and cells and more importantly, their intracellular release at sites of interest still remains a major challenge that needs to be addressed before this technique could become a clinically viable option. In the current study, we have engineered and screened a series of CD44 targeting hyaluronic acid (HA) based self-assembling nanosystems for targeted siRNA delivery. The HA polymer was functionalized with lipids of varying carbon chain lengths/nitrogen content, as well as polyamines for assessing siRNA encapsulation. From the screens, several HA-derivatives were identified that could stably encapsulate/complex siRNAs and form self-assembled nanosystems, as determined by gel retardation assays and dynamic light scattering. Many HA derivatives could transfect siRNAs into cancer cells overexpressing CD44 receptors. Interestingly, blocking the CD44 receptors on the cells using free excess soluble HA prior to incubation of cy3-labeled-siRNA loaded HA nano-assemblies resulted in >90% inhibition of the receptor mediated uptake, confirming target specificity. In addition, SSB/PLK1 siRNA encapsulated in HA-PEI/PEG nanosystems demonstrated dose dependent and target specific gene knockdown in both sensitive and resistant A549 lung cancer cells overexpressing CD44 receptors. More importantly, these siRNA encapsulated nanosystems demonstrated tumor selective uptake and target specific gene knock down in vivo in solid tumors as well as in metastatic tumors. The HA based nanosystems thus portend to be promising siRNA delivery vectors for systemic targeting of CD44 overexpressing cancers including tumor initiating (stem-) cells and metastatic lesions. PMID:23410679

  17. ARNetMiT R Package: association rules based gene co-expression networks of miRNA targets.

    Science.gov (United States)

    Özgür Cingiz, M; Biricik, G; Diri, B

    2017-03-31

    miRNAs are key regulators that bind to target genes to suppress their gene expression level. The relations between miRNA-target genes enable users to derive co-expressed genes that may be involved in similar biological processes and functions in cells. We hypothesize that target genes of miRNAs are co-expressed, when they are regulated by multiple miRNAs. With the usage of these co-expressed genes, we can theoretically construct co-expression networks (GCNs) related to 152 diseases. In this study, we introduce ARNetMiT that utilize a hash based association rule algorithm in a novel way to infer the GCNs on miRNA-target genes data. We also present R package of ARNetMiT, which infers and visualizes GCNs of diseases that are selected by users. Our approach assumes miRNAs as transactions and target genes as their items. Support and confidence values are used to prune association rules on miRNA-target genes data to construct support based GCNs (sGCNs) along with support and confidence based GCNs (scGCNs). We use overlap analysis and the topological features for the performance analysis of GCNs. We also infer GCNs with popular GNI algorithms for comparison with the GCNs of ARNetMiT. Overlap analysis results show that ARNetMiT outperforms the compared GNI algorithms. We see that using high confidence values in scGCNs increase the ratio of the overlapped gene-gene interactions between the compared methods. According to the evaluation of the topological features of ARNetMiT based GCNs, the degrees of nodes have power-law distribution. The hub genes discovered by ARNetMiT based GCNs are consistent with the literature.

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

    Directory of Open Access Journals (Sweden)

    Yang Zhang

    2016-10-01

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

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

    Science.gov (United States)

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

    2016-10-27

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

  20. New targets for immunotherapy-based treatment of HPV-related cancers | Center for Cancer Research

    Science.gov (United States)

    Scientists at the Center for Cancer Research and three other cancer research institutions show that immunotherapy treatments that resulted in complete regression of metastatic cervical cancer largely targeted two non-viral antigens. Read more…  

  1. Factor Analysis of Therapist-Identified Treatment Targets in Community-Based Children's Mental Health.

    Science.gov (United States)

    Love, Allison R; Okado, Izumi; Orimoto, Trina E; Mueller, Charles W

    2018-01-01

    The present study used exploratory and confirmatory factor analyses to identify underlying latent factors affecting variation in community therapists' endorsement of treatment targets. As part of a statewide practice management program, therapist completed monthly reports of treatment targets (up to 10 per month) for a sample of youth (n = 790) receiving intensive in-home therapy. Nearly 75 % of youth were diagnosed with multiple co-occurring disorders. Five factors emerged: Disinhibition, Societal Rules Evasion, Social Engagement Deficits, Emotional Distress, and Management of Biodevelopmental Outcomes. Using logistic regression, primary diagnosis predicted therapist selection of Disinhibition and Emotional Distress targets. Client age predicted endorsement of Societal Rules Evasion targets. Practice-to-research implications are discussed.

  2. A QFD-Based Mathematical Model for New Product Development Considering the Target Market Segment

    Directory of Open Access Journals (Sweden)

    Liang-Hsuan Chen

    2014-01-01

    Full Text Available Responding to customer needs is important for business success. Quality function deployment provides systematic procedures for converting customer needs into technical requirements to ensure maximum customer satisfaction. The existing literature mainly focuses on the achievement of maximum customer satisfaction under a budgetary limit via mathematical models. The market goal of the new product for the target market segment is usually ignored. In this study, the proposed approach thus considers the target customer satisfaction degree for the target market segment in the model by formulating the overall customer satisfaction as a function of the quality level. In addition, the proposed approach emphasizes the cost-effectiveness concept in the design stage via the achievement of the target customer satisfaction degree using the minimal total cost. A numerical example is used to demonstrate the applicability of the proposed approach and its characteristics are discussed.

  3. An Integral Model for Target Tracking Based on the Use of a WSN

    Directory of Open Access Journals (Sweden)

    Pietro Manzoni

    2013-06-01

    Full Text Available The use of wireless sensor networks (WSN in tracking applications is growing at a fast pace. In these applications, the sensor nodes discover, monitor and track an event or target object. A significant number of proposals relating the use of WSNs for target tracking have been published to date. However, they either focus on the tracking algorithm or on the communication protocol, and none of them address the problem integrally. In this paper, a comprehensive proposal for target detection and tracking is discussed. We introduce a tracking algorithm to detect and estimate a target location. Moreover, we introduce a low-overhead routing protocol to be used along with our tracking algorithm. The proposed algorithm has low computational complexity and has been designed considering the use of a mobile sink while generating minimal delay and packet loss. We also discuss the results of the evaluation of the proposed algorithms.

  4. Quantum dot-based multiphoton fluorescent pipettes for targeted neuronal electrophysiology.

    Science.gov (United States)

    Andrásfalvy, Bertalan K; Galiñanes, Gregorio L; Huber, Daniel; Barbic, Mladen; Macklin, John J; Susumu, Kimihiro; Delehanty, James B; Huston, Alan L; Makara, Judit K; Medintz, Igor L

    2014-12-01

    Targeting visually identified neurons for electrophysiological recording is a fundamental neuroscience technique; however, its potential is hampered by poor visualization of pipette tips in deep brain tissue. We describe quantum dot-coated glass pipettes that provide strong two-photon contrast at deeper penetration depths than those achievable with current methods. We demonstrated the pipettes' utility in targeted patch-clamp recording experiments and single-cell electroporation of identified rat and mouse neurons in vitro and in vivo.

  5. Development of beryllium-based neutron target system with three-layer structure for accelerator-based neutron source for boron neutron capture therapy.

    Science.gov (United States)

    Kumada, Hiroaki; Kurihara, Toshikazu; Yoshioka, Masakazu; Kobayashi, Hitoshi; Matsumoto, Hiroshi; Sugano, Tomei; Sakurai, Hideyuki; Sakae, Takeji; Matsumura, Akira

    2015-12-01

    The iBNCT project team with University of Tsukuba is developing an accelerator-based neutron source. Regarding neutron target material, our project has applied beryllium. To deal with large heat load and blistering of the target system, we developed a three-layer structure for the target system that includes a blistering mitigation material between the beryllium used as the neutron generator and the copper heat sink. The three materials were bonded through diffusion bonding using a hot isostatic pressing method. Based on several verifications, our project chose palladium as the intermediate layer. A prototype of the neutron target system was produced. We will verify that sufficient neutrons for BNCT treatment are generated by the device in the near future. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Simulation-based sensor modeling and at-range target detection characterization with MuSES

    Science.gov (United States)

    Packard, Corey D.; Curran, Allen R.; Saur, Nicholas E.; Rynes, Peter L.

    2015-05-01

    Accurate infrared signature prediction of targets, such as humans or ground vehicles, depends primarily on the realistic prediction of physical temperatures. Thermal model development typically requires a geometric description of the target (i.e., a 3D surface mesh) along with material properties for characterizing the thermal response to simulated weather conditions. Once an accurate thermal solution has been obtained, signature predictions for an EO/IR spectral waveband can be generated. The image rendering algorithm should consider the radiative emissions, diffuse/specular reflections, and atmospheric effects to depict how an object in a natural scene would be perceived by an EO/IR sensor. The EO/IR rendering process within MuSES, developed by ThermoAnalytics, can be used to create a synthetic radiance image that predicts the energy detected by a specific sensor just prior to passing through its optics. For additional realism, blurring due to lens diffraction and noise due to variations in photon detection can also be included, via specification of sensor characteristics. Additionally, probability of detection can be obtained via the Targeting Task Performance (TTP) metric, making it possible to predict a target's at-range detectability to a particular threat sensor. In this paper, we will investigate the at-range contrast and detectability of some example targets and examine the effect of various techniques such as sub-pixel sampling and target pixel thresholding.

  7. Dendritic cell based PSMA immunotherapy for prostate cancer using a CD40-targeted adenovirus vector.

    Directory of Open Access Journals (Sweden)

    Briana Jill Williams

    Full Text Available Human prostate tumor vaccine and gene therapy trials using ex vivo methods to prime dendritic cells (DCs with prostate specific membrane antigen (PSMA have been somewhat successful, but to date the lengthy ex vivo manipulation of DCs has limited the widespread clinical utility of this approach. Our goal was to improve upon cancer vaccination with tumor antigens by delivering PSMA via a CD40-targeted adenovirus vector directly to DCs as an efficient means for activation and antigen presentation to T-cells. To test this approach, we developed a mouse model of prostate cancer by generating clonal derivatives of the mouse RM-1 prostate cancer cell line expressing human PSMA (RM-1-PSMA cells. To maximize antigen presentation in target cells, both MHC class I and TAP protein expression was induced in RM-1 cells by transduction with an Ad vector expressing interferon-gamma (Ad5-IFNγ. Administering DCs infected ex vivo with CD40-targeted Ad5-huPSMA, as well as direct intraperitoneal injection of the vector, resulted in high levels of tumor-specific CTL responses against RM-1-PSMA cells pretreated with Ad5-IFNγ as target cells. CD40 targeting significantly improved the therapeutic antitumor efficacy of Ad5-huPSMA encoding PSMA when combined with Ad5-IFNγ in the RM-1-PSMA model. These results suggest that a CD-targeted adenovirus delivering PSMA may be effective clinically for prostate cancer immunotherapy.

  8. Sensitive targeted multiple protein quantification based on elemental detection of Quantum Dots

    Energy Technology Data Exchange (ETDEWEB)

    Montoro Bustos, Antonio R.; Garcia-Cortes, Marta [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); González-Iglesias, Hector [Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernandez-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo 33012 (Spain); Ruiz Encinar, Jorge, E-mail: ruizjorge@uniovi.es [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); Costa-Fernández, José M. [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain); Coca-Prados, Miguel [Fundación de Investigación Oftalmológica, Instituto Oftalmológico Fernandez-Vega, Avenida Doctores Fernández-Vega, 34, Oviedo 33012 (Spain); Department of Ophthalmology and Visual Science, Yale University School of Medicine, New Haven, CT 06510 (United States); Sanz-Medel, Alfredo, E-mail: asm@uniovi.es [Department of Physical and Analytical Chemistry, University of Oviedo, Julián Clavería 8, Oviedo 33006 (Spain)

    2015-06-16

    Highlights: • Novel generic platform for multiparametric quantification of proteins. • QDs labeling and ICP-MS detection allow significant analytical signal amplification. • ICP-MS mass balances information provided an internal validation of the immunoassay. • Multiparametric determination of 5 proteins in human serum samples. • ICP-MS reduced matrix effects as compared to other conventional detection techniques. - Abstract: A generic strategy based on the use of CdSe/ZnS Quantum Dots (QDs) as elemental labels for protein quantification, using immunoassays with elemental mass spectrometry (ICP-MS), detection is presented. In this strategy, streptavidin modified QDs (QDs-SA) are bioconjugated to a biotinylated secondary antibody (b-Ab{sub 2}). After a multi-technique characterization of the synthesized generic platform (QDs-SA-b-Ab{sub 2}) it was applied to the sequential quantification of five proteins (transferrin, complement C3, apolipoprotein A1, transthyretin and apolipoprotein A4) at different concentration levels in human serum samples. It is shown how this generic strategy does only require the appropriate unlabeled primary antibody for each protein to be detected. Therefore, it introduces a way out to the need for the cumbersome and specific bioconjugation of the QDs to the corresponding specific recognition antibody for every target analyte (protein). Results obtained were validated with those obtained using UV–vis spectrophotometry and commercial ELISA Kits. As expected, ICP-MS offered one order of magnitude lower DL (0.23 fmol absolute for transferrin) than the classical spectrophotometric detection (3.2 fmol absolute). ICP-MS precision and detection limits, however turned out to be compromised by procedural blanks. The full analytical performance of the ICP-MS-based immunoassay proposed was assessed for detection of transferrin (Tf), present at the low ng mL{sup −1} range in a complex “model” synthetic matrix, where the total protein

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

    Directory of Open Access Journals (Sweden)

    Sungho Kim

    2018-01-01

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

  10. 40 CFR 745.227 - Work practice standards for conducting lead-based paint activities: target housing and child...

    Science.gov (United States)

    2010-07-01

    ..., child-occupied facilities) on/in which abatement work will be performed. (F) Property name (if... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Work practice standards for conducting lead-based paint activities: target housing and child-occupied facilities. 745.227 Section 745.227...

  11. 75 FR 13127 - Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied...

    Science.gov (United States)

    2010-03-18

    ... AGENCY Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied... for a renovation, repair and painting program in accordance with section 402(c)(3) of TSCA, 15 U.S.C... administer and enforce requirements for a renovation, repair and painting program in accordance with section...

  12. 75 FR 51808 - Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied...

    Science.gov (United States)

    2010-08-23

    ...-9] Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied... for renovation, repair and painting programs in accordance with section 402(c)(3) of TSCA, 15 U.S.C... CFR 745.324(d)(2), to administer and enforce requirements for a renovation, repair and painting...

  13. 76 FR 12106 - Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied...

    Science.gov (United States)

    2011-03-04

    ... AGENCY Lead-Based Paint Renovation, Repair and Painting Activities in Target Housing and Child Occupied..., repair and painting program in accordance with section 402(c)(3) of TSCA. This notice also announces that... a renovation, repair and painting program in accordance with section 402(c)(3) of TSCA. This notice...

  14. Microwave Imaging of Three-Dimensional Targets by Means of an Inexact-Newton-Based Inversion Algorithm

    Directory of Open Access Journals (Sweden)

    Claudio Estatico

    2013-01-01

    Full Text Available A microwave imaging method previously developed for tomographic inspection of dielectric targets is extended to three-dimensional objects. The approach is based on the full vector equations of the electromagnetic inverse scattering problem. The ill-posedness of the problem is faced by the application of an inexact-Newton method. Preliminary reconstruction results are reported.

  15. A fluorescent biosensing platform based on the polydopamine nanospheres intergrating with Exonuclease III-assisted target recycling amplification.

    Science.gov (United States)

    Qiang, Weibing; Wang, Xi; Li, Wei; Chen, Xiang; Li, Hui; Xu, Danke

    2015-09-15

    Rapid, cost-effective, sensitive and specific analysis of biomolecules is important in the modern healthcare system. Here, a fluorescent biosensing platform based on the polydopamine nanospheres (PDANS) intergrating with Exonuclease III (Exo III) was developed. Due to the interaction between the ssDNA and the PDANS, the fluorescence of 6-carboxyfluorescein (FAM) labelled in the probe would been quenched by PDANS through FRET. While, in the present of the target DNA, the probe DNA would hybridize with the target DNA to form the double-strand DNA complex. Thus, Exo III could catalyze the stepwise removal of mononucleotides from 3'-terminus in the probe DNA, releasing the target DNA. As the FAM was released from the probe DNA, the fluorescence would no longer been quenched, led to the signal on. As one target DNA molecule could undergo a number of cycles to trigger the degradation of abundant probe DNA, Exo III-assisted target recycling would led to the amplification of the signal. The detection limit for DNA was 5 pM, which was 20 times lower than that without Exo III. And the assay time was largely shortened due to the faster signal recovery kinetics. What is more, this target recycling strategy was also applied to conduct an aptamer-based biosensing platform. The fluorescence intensity was also enhanced for the assay of adenosine triphosphate (ATP). For the Exo III-assisted target recycling amplification, DNA and ATP were fast detected with high sensitivity and selectivity. This work provides opportunities to develop simple, rapid, economical, and sensitive biosensing platforms for biomedical diagnostics. Copyright © 2015 Elsevier B.V. All rights reserved.

  16. Allowable CO2 emissions based on regional and impact-related climate targets: The role of land processes

    Science.gov (United States)

    Seneviratne, S. I.; Donat, M.; Pitman, A.; Knutti, R.; Wilby, R.; Vogel, M.; Orth, R.

    2016-12-01

    Global temperature targets, such as the widely accepted "2° and 1.5° targets", may fail to communicate the urgency of reducing CO2 emissions because they are disconnected from their implications. The translation of CO2 emissions into regional- and impact-related climate targets is more powerful because such targets are more directly aligned with individual national interests. A recent publication (Seneviratne et al. 2016, Nature) reveals that regional changes in extreme temperatures and precipitation scale robustly with global temperature across scenarios, and thus with cumulative CO2 emissions. They thus allow a better communication of implied regional impacts associated with global targets for CO2 emissions. However, the regional responses are very varied and display strong differences in regional temperature and hydrological sensitivity. Process-based based analyses explain these divergences and highlight avenues for reducing uncertainties in regional projections of extremes, in particular related to the role of land-atmosphere feedbacks. These results have important implications for the design of regional mitigation and climate adaptation policies, for instance related to land use changes. Reference: Seneviratne, S.I., M.G. Donat, A.J. Pitman, R. Knutti, and R. Wilby, 2016, Nature, 529, 477-483, doi:10.1038/nature16542

  17. Development of a target-site based regional frequency model using historical information

    Science.gov (United States)

    Hamdi, Yasser; Bardet, Lise; Duluc, Claire-Marie; Rebour, Vincent

    2016-04-01

    Nuclear power facilities in France were designed to withstand extreme environmental conditions with a very low probability of failure. Nevertheless, some exceptional surges considered as outliers are not properly addressed by classical frequency analysis models. If available data at the site of interest (target-site) is sufficiently complete on a long period and not characterized by the presence of an outlier, at-site frequency analysis can be used to estimate quantiles with acceptable uncertainties. Otherwise, regional and historical information (HI) may be used to mitigate the lack of data and the influence of the outlier by increasing its representativeness in the sample. several models have been proposed over the last years for regional extreme surges frequency analysis in France to take into account these outliers in the frequency analysis. However, these models do not give a specific weight to the target site and cannot take into account HI. The objective of the present work is to develop a regional frequency model (RFM) centered on a target-site and using HI. The neighborhood between sites is measured by a degree of physical and statistical dependence between observations (with a prior confidence level). Unlike existing models, the obtained region around the target site (and constituting the neighboring sites) is sliding from a target-site to another. In other words, the developed model assigns a region for each target site. The idea behind the construction of a frequency model favoring target sites and the principle of moving regions around these target-sites is the original key point of the developed model. A related issue regards the estimation of missed and/or ungauged surges at target-sites from those of gauged potential neighboring sites, a multiple linear regression (MLR) is used and it can be extended to other reconstitutions models. MLR analysis can be considered conclusive only if available observations at neighboring sites are informative enough

  18. A global calibration method for multiple vision sensors based on multiple targets

    International Nuclear Information System (INIS)

    Liu, Zhen; Zhang, Guangjun; Wei, Zhenzhong; Sun, Junhua

    2011-01-01

    The global calibration of multiple vision sensors (MVS) has been widely studied in the last two decades. In this paper, we present a global calibration method for MVS with non-overlapping fields of view (FOVs) using multiple targets (MT). MT is constructed by fixing several targets, called sub-targets, together. The mutual coordinate transformations between sub-targets need not be known. The main procedures of the proposed method are as follows: one vision sensor is selected from MVS to establish the global coordinate frame (GCF). MT is placed in front of the vision sensors for several (at least four) times. Using the constraint that the relative positions of all sub-targets are invariant, the transformation matrix from the coordinate frame of each vision sensor to GCF can be solved. Both synthetic and real experiments are carried out and good result is obtained. The proposed method has been applied to several real measurement systems and shown to be both flexible and accurate. It can serve as an attractive alternative to existing global calibration methods

  19. Total variation-based method for radar coincidence imaging with model mismatch for extended target

    Science.gov (United States)

    Cao, Kaicheng; Zhou, Xiaoli; Cheng, Yongqiang; Fan, Bo; Qin, Yuliang

    2017-11-01

    Originating from traditional optical coincidence imaging, radar coincidence imaging (RCI) is a staring/forward-looking imaging technique. In RCI, the reference matrix must be computed precisely to reconstruct the image as preferred; unfortunately, such precision is almost impossible due to the existence of model mismatch in practical applications. Although some conventional sparse recovery algorithms are proposed to solve the model-mismatch problem, they are inapplicable to nonsparse targets. We therefore sought to derive the signal model of RCI with model mismatch by replacing the sparsity constraint item with total variation (TV) regularization in the sparse total least squares optimization problem; in this manner, we obtain the objective function of RCI with model mismatch for an extended target. A more robust and efficient algorithm called TV-TLS is proposed, in which the objective function is divided into two parts and the perturbation matrix and scattering coefficients are updated alternately. Moreover, due to the ability of TV regularization to recover sparse signal or image with sparse gradient, TV-TLS method is also applicable to sparse recovering. Results of numerical experiments demonstrate that, for uniform extended targets, sparse targets, and real extended targets, the algorithm can achieve preferred imaging performance both in suppressing noise and in adapting to model mismatch.

  20. Research on the underwater target imaging based on the streak tube laser lidar

    Science.gov (United States)

    Cui, Zihao; Tian, Zhaoshuo; Zhang, Yanchao; Bi, Zongjie; Yang, Gang; Gu, Erdan

    2018-03-01

    A high frame rate streak tube imaging lidar (STIL) for real-time 3D imaging of underwater targets is presented in this paper. The system uses 532nm pulse laser as the light source, the maximum repetition rate is 120Hz, and the pulse width is 8ns. LabVIEW platform is used in the system, the system control, synchronous image acquisition, 3D data processing and display are realized through PC. 3D imaging experiment of underwater target is carried out in a flume with attenuation coefficient of 0.2, and the images of different depth and different material targets are obtained, the imaging frame rate is 100Hz, and the maximum detection depth is 31m. For an underwater target with a distance of 22m, the high resolution 3D image real-time acquisition is realized with range resolution of 1cm and space resolution of 0.3cm, the spatial relationship of the targets can be clearly identified by the image. The experimental results show that STIL has a good application prospect in underwater terrain detection, underwater search and rescue, and other fields.

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

    Science.gov (United States)

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

    2014-03-20

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

  2. Mid-infrared imaging system based on polarizers for detecting marine targets covered in sun glint.

    Science.gov (United States)

    Zhao, Huijie; Ji, Zheng; Zhang, Ying; Sun, Xiaofeng; Song, Pengfei; Li, Yansong

    2016-07-25

    When a marine target is detected by a mid-infrared detector on a sunny day, the target's information could be lost if it is located in sun glint. Therefore, we developed a new mid-infrared imaging system capable of effectively detecting marine targets in regions of strong sun glint, which is presented in this report. Firstly, the theory of the analysis methods employed in different detection scenarios is briefly described to establish whether one or two polarizers should be utilized to suppress further the p-polarized component of sun glint. Secondly, for the case in which a second polarizer is employed, the formula for the optimum angle between the two polarizers is given. Then, the results of our field experiment are presented, demonstrating that the developed system can significantly reduce sun glint and can enhance the contrast of target images. A commonly used image processing algorithm proved capable of identifying a target in sun glint, confirming the effectiveness of our proposed mid-infrared polarization imaging system.

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

    OpenAIRE

    Lawton, Rebecca J.; Mata, Leonardo; de Nys, Rocky; Paul, Nicholas A.

    2013-01-01

    The optimised reduction of dissolved nutrient loads in aquaculture effluents through bioremediation requires selection of appropriate algal species and strains. The objective of the current study was to identify target species and strains from the macroalgal genus Ulva for bioremediation of land-based aquaculture facilities in Eastern Australia. We surveyed land-based aquaculture facilities and natural coastal environments across three geographic locations in Eastern Australia to determine wh...

  4. Feature extraction for SAR target recognition based on supervised manifold learning

    International Nuclear Information System (INIS)

    Du, C; Zhou, S; Sun, J; Zhao, J

    2014-01-01

    On the basis of manifold learning theory, a new feature extraction method for Synthetic aperture radar (SAR) target recognition is proposed. First, the proposed algorithm estimates the within-class and between-class local neighbourhood surrounding each SAR sample. After computing the local tangent space for each neighbourhood, the proposed algorithm seeks for the optimal projecting matrix by preserving the local within-class property and simultaneously maximizing the local between-class separability. The use of uncorrelated constraint can also enhance the discriminating power of the optimal projecting matrix. Finally, the nearest neighbour classifier is applied to recognize SAR targets in the projected feature subspace. Experimental results on MSTAR datasets demonstrate that the proposed method can provide a higher recognition rate than traditional feature extraction algorithms in SAR target recognition

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

    Directory of Open Access Journals (Sweden)

    Yong-Yeol Ahn

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

  6. Cardio-oncology Related to Heart Failure: Epidermal Growth Factor Receptor Target-Based Therapy.

    Science.gov (United States)

    Kenigsberg, Benjamin; Jain, Varun; Barac, Ana

    2017-04-01

    Cancer therapy targeting the epidermal growth factor receptor (EGFR)/erythroblastic leukemia viral oncogene B (ErbB)/human EGFR receptor (HER) family of tyrosine kinases has been successfully used in treatment of several malignancies. The ErbB pathways play a role in the maintenance of cardiac homeostasis. This article summarizes current knowledge about EGFR/ErbB/HER receptor-targeted cancer therapeutics focusing on their cardiotoxicity profiles, molecular mechanisms, and implications in clinical cardio-oncology. The article discusses challenges in predicting, monitoring, and treating cardiac dysfunction and heart failure associated with ErbB-targeted cancer therapeutics and highlights opportunities for researchers and clinical investigators. Copyright © 2016 Elsevier Inc. All rights reserved.

  7. The biological effectiveness of targeted radionuclide therapy based on a whole-body pharmacokinetic model

    Science.gov (United States)

    Grudzinski, Joseph J; Tomé, Wolfgang; Weichert, Jamey P; Jeraj, Robert

    2013-01-01

    Biologically effective dose (BED) may be more of a relevant quantity than absorbed dose for establishing tumour response relationships. By taking into account the dose rate and tissue-specific parameters such as repair and radiosensitivity, it is possible to compare the relative biological effects of different targeted radionuclide therapy (TRT) agents. The aim of this work was to develop an analytical tumour BED calculation for TRT that could predict a relative biological effect based on normal body and tumour pharmacokinetics. This work represents a step in the direction of establishing relative pharmacokinetic criteria of when the BED formalism is more applicable than absorbed dose for TRT. A previously established pharmacokinetic (PK) model for TRT was used and adapted into the BED formalism. An analytical equation for the protraction factor, which incorporates dose rate and repair rate, was derived. Dose rates within the normal body and tumour were related to the slopes of their time–activity curves which were determined by the ratios of their respective PK parameters. The relationships between the tumour influx-to-efflux ratio (k34:k43), central compartment efflux-to-influx ratio (k12:k21), central elimination (kel), and tumour repair rate (μ), and tumour BED were investigated. As the k34:k43 ratio increases and the k12:k21 ratio decreases, the difference between tumour BED and D increases. In contrast, as the k34:k43 ratios decrease and the k12:k21 ratios increase, the tumour BED approaches D. At large k34:k43 ratios, the difference between tumour BED and D increases to a maximum as kel increases. At small k34:k43 ratios, the tumour BED approaches D at very small kel. At small μ and small k34:k43 ratios, the tumour BED approaches D. For large k34:k43 ratios, large μ values cause tumour BED to approach D. This work represents a step in the direction of establishing relative PK criteria of when the BED formalism is more applicable than absorbed dose for

  8. Activity Based Protein Profiling Leads to Identification of Novel Protein Targets for Nerve Agent VX.

    Science.gov (United States)

    Carmany, Dan; Walz, Andrew J; Hsu, Fu-Lian; Benton, Bernard; Burnett, David; Gibbons, Jennifer; Noort, Daan; Glaros, Trevor; Sekowski, Jennifer W

    2017-04-17

    Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt symptoms is the disruption of cholinergic pathways. While much is known about the primary toxicity mechanisms of nerve agents, there remains a paucity of information regarding impacts on other pathways and systemic effects. These are important for establishing a comprehensive understanding of the toxic mechanisms of OP nerve agents. To identify novel proteins that interact with VX, and that may give insight into these other mechanisms, we used activity-based protein profiling (ABPP) employing a novel VX-probe on lysates from rat heart, liver, kidney, diaphragm, and brain tissue. By making use of a biotin linked VX-probe, proteins covalently bound by the probe were isolated and enriched using streptavidin beads. The proteins were then digested, labeled with isobarically distinct tandem mass tag (TMT) labels, and analyzed by liquid chromatography tandem mass spectrometry (LC-MS/MS). Quantitative analysis identified 132 bound proteins, with many proteins found in multiple tissues. As with previously published ABPP OP work, monoacylglycerol lipase associated proteins and fatty acid amide hydrolase (FAAH) were shown to be targets of VX. In addition to these two and other predicted neurotransmitter-related proteins, a number of proteins involved with energy metabolism were identified. Four of these enzymes, mitochondrial isocitrate dehydrogenase 2 (IDH2), isocitrate dehydrogenase 3 (IDH3), malate dehydrogenase (MDH), and succinyl CoA (SCS) ligase, were assayed for VX inhibition. Only IDH2 NADP+ activity was shown to be inhibited directly. This result is consistent with other work reporting animals exposed to OP compounds exhibit

  9. Investigating a multi-purpose target for electron linac based photoneutron sources for BNCT of deep-seated tumors

    International Nuclear Information System (INIS)

    Masoudi, S. Farhad; Rasouli, Fatemeh S.

    2015-01-01

    Recent studies in BNCT have focused on investigating appropriate neutron sources as alternatives for nuclear reactors. As the most prominent facilities, the electron linac based photoneutron sources benefit from two consecutive reactions, (e, γ) and (γ, n). The photoneutron sources designed so far are composed of bipartite targets which involve practical problems and are far from the objective of achieving an optimized neutron source. This simulation study deals with designing a compact, optimized, and geometrically simple target for a photoneutron source based on an electron linac. Based on a set of MCNPX simulations, tungsten is found to have the potential of utilizing as both photon converter and photoneutron target. Besides, it is shown that an optimized dimension for such a target slows-down the produced neutrons toward the desired energy range while keeping them economy, which makes achieving the recommended criteria for BNCT of deep-tumors more available. This multi-purpose target does not involve complicated designing, and can be considered as a significant step toward finding application of photoneutron sources for in-hospital treatments. In order to shape the neutron beam emitted from such a target, the beam is planned to pass through an optimized arrangement of materials composed of moderators, filters, reflector, and collimator. By assessment with the recommended in-air parameters, it is shown that the designed beam provides high intensity of desired neutrons, as well as low background contamination. The last section of this study is devoted to investigate the performance of the resultant beam in deep tissue. A typical simulated liver tumor, located within a phantom of human body, was subjected to the irradiation of the designed spectrum. The dosimetric results, including evaluated depth-dose curves and carried out in-phantom parameters show that the proposed configuration establishes acceptable agreement between the appropriate neutron intensity, and

  10. Imporved method for stereo vision-based human detection for a mobile robot following a target person

    Directory of Open Access Journals (Sweden)

    Ali, Badar

    2015-05-01

    Full Text Available Interaction between humans and robots is a fundamental need for assistive and service robots. Their ability to detect and track people is a basic requirement for interaction with human beings. This article presents a new approach to human detection and targeted person tracking by a mobile robot. Our work is based on earlier methods that used stereo vision-based tracking linked directly with Hu moment-based detection. The earlier technique was based on the assumption that only one person is present in the environment – the target person – and it was not able to handle more than this one person. In our novel method, we solved this problem by using the Haar-based human detection method, and included a target person selection step before initialising tracking. Furthermore, rather than linking the Kalman filter directly with human detection, we implemented the tracking method before the Kalman filter-based estimation. We used the Pioneer 3AT robot, equipped with stereo camera and sonars, as the test platform.

  11. Demonstration of a high-intensity neutron source based on a liquid-lithium target for Accelerator based Boron Neutron Capture Therapy.

    Science.gov (United States)

    Halfon, S; Arenshtam, A; Kijel, D; Paul, M; Weissman, L; Berkovits, D; Eliyahu, I; Feinberg, G; Kreisel, A; Mardor, I; Shimel, G; Shor, A; Silverman, I; Tessler, M

    2015-12-01

    A free surface liquid-lithium jet target is operating routinely at Soreq Applied Research Accelerator Facility (SARAF), bombarded with a ~1.91 MeV, ~1.2 mA continuous-wave narrow proton beam. The experiments demonstrate the liquid lithium target (LiLiT) capability to constitute an intense source of epithermal neutrons, for Accelerator based Boron Neutron Capture Therapy (BNCT). The target dissipates extremely high ion beam power densities (>3 kW/cm(2), >0.5 MW/cm(3)) for long periods of time, while maintaining stable conditions and localized residual activity. LiLiT generates ~3×10(10) n/s, which is more than one order of magnitude larger than conventional (7)Li(p,n)-based near threshold neutron sources. A shield and moderator assembly for BNCT, with LiLiT irradiated with protons at 1.91 MeV, was designed based on Monte Carlo (MCNP) simulations of BNCT-doses produced in a phantom. According to these simulations it was found that a ~15 mA near threshold proton current will apply the therapeutic doses in ~1h treatment duration. According to our present results, such high current beams can be dissipated in a liquid-lithium target, hence the target design is readily applicable for accelerator-based BNCT. Copyright © 2015 Elsevier Ltd. All rights reserved.

  12. SU-F-T-36: Dosimetric Comparison of Point Based Vs. Target Based Prescription for Intracavitary Brachytherapy in Cancer of the Cervix

    Energy Technology Data Exchange (ETDEWEB)

    Ashenafi, M; McDonald, D; Peng, J; Mart, C; Koch, N; Cooper, L; Vanek, K [Medical University of South Carolina, Charleston, SC (United States)

    2016-06-15

    Purpose: Improved patient imaging used for planning the treatment of cervical cancer with Tandem and Ovoid (T&O) Intracavitary high-dose-rate brachytherapy (HDR) now allows for 3D delineation of target volumes and organs-at-risk. However, historical data relies on the conventional point A-based planning technique. A comparative dosimetric study was performed by generating both target-based (TBP) and point-based (PBP) plans for ten clinical patients. Methods: Treatment plans created using Elekta Oncentra v. 4.3 for ten consecutive cervical cancer patients were analyzed. All patients were treated with HDR using the Utrecht T&O applicator. Both CT and MRI imaging modalities were utilized to delineate clinical target volume (CTV) and organs-at-risk (rectum, sigmoid, bladder, and small bowel). Point A (left and right), vaginal mucosa, and ICRU rectum and bladder points were defined on CT. Two plans were generated for each patient using two prescription methods (PBP and TBP). 7Gy was prescribed to each point A for each PBP plan and to the target D90% for each TBP plan. Target V90%, V100%, and V200% were evaluated. In addition, D0.1cc and D2cc were analyzed for each organ-at-risk. Differences were assessed for statistical significance (p<0.05) by use of Student’s t-test. Results: Target coverage was comparable for both planning methods, with each method providing adequate target coverage. TBP showed lower absolute dose to the target volume than PBP (D90% = 7.0Gy vs. 7.4Gy, p=0.028), (V200% = 10.9cc vs. 12.8cc, p=0.014), (ALeft = 6.4Gy vs. 7Gy, p=0.009), and (ARight = 6.4Gy vs. 7Gy, p=0.013). TBP also showed a statistically significant reduction in bladder, rectum, small bowel, and sigmoid doses compared to PBP. There was no statistically significant difference in vaginal mucosa or ICRU-defined rectum and bladder dose. Conclusion: Target based prescription resulted in substantially lower dose to delineated organs-at-risk compared to point based prescription, while

  13. Optimization of ISOL targets based on Monte-Carlo simulations of ion release curves

    CERN Document Server

    Mustapha, B

    2003-01-01

    A detailed model for simulating release curves from ISOL targets has been developed. The full 3D geometry is implemented using Geant-4. Produced particles are followed individually from production to release. The delay time is computed event by event. All processes involved: diffusion, effusion and decay are included to obtain the overall release curve. By fitting to the experimental data, important parameters of the release process (diffusion coefficient, sticking time, ...) are extracted. They can be used to improve the efficiency of existing targets and design new ones more suitable to produce beams of rare isotopes.

  14. Optimization of ISOL targets based on Monte-Carlo simulations of ion release curves

    International Nuclear Information System (INIS)

    Mustapha, B.; Nolen, J.A.

    2003-01-01

    A detailed model for simulating release curves from ISOL targets has been developed. The full 3D geometry is implemented using Geant-4. Produced particles are followed individually from production to release. The delay time is computed event by event. All processes involved: diffusion, effusion and decay are included to obtain the overall release curve. By fitting to the experimental data, important parameters of the release process (diffusion coefficient, sticking time, ...) are extracted. They can be used to improve the efficiency of existing targets and design new ones more suitable to produce beams of rare isotopes

  15. Targeted Molecular Imaging of Cancer Cells Using MS2-Based 129 Xe NMR

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Keunhong [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Netirojjanakul, Chawita [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Munch, Henrik K. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Sun, Jinny [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Finbloom, Joel A. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Wemmer, David E. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Physical Biosciences Division; Pines, Alexander [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division; Francis, Matthew B. [Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Lawrence Berkeley National Lab. (LBNL), Berkeley, CA (United States). Materials Sciences Division

    2016-07-25

    Targeted, selective, and highly sensitive 129Xe NMR nanoscale biosensors have been synthesized using a spherical MS2 viral capsid, Cryptophane A molecules, and DNA aptamers. The biosensors showed strong binding specificity toward targeted lymphoma cells (Ramos line). Hyperpolarized 129Xe NMR signal contrast and hyper-CEST 129Xe MRI image contrast indicated its promise as highly sensitive hyperpolarized 129Xe NMR nanoscale biosensor for future applications in cancer detection in vivo.

  16. System simulation method for fiber-based homodyne multiple target interferometers using short coherence length laser sources

    Science.gov (United States)

    Fox, Maik; Beuth, Thorsten; Streck, Andreas; Stork, Wilhelm

    2015-09-01

    Homodyne laser interferometers for velocimetry are well-known optical systems used in many applications. While the detector power output signal of such a system, using a long coherence length laser and a single target, is easily modelled using the Doppler shift, scenarios with a short coherence length source, e.g. an unstabilized semiconductor laser, and multiple weak targets demand a more elaborated approach for simulation. Especially when using fiber components, the actual setup is an important factor for system performance as effects like return losses and multiple way propagation have to be taken into account. If the power received from the targets is in the same region as stray light created in the fiber setup, a complete system simulation becomes a necessity. In previous work, a phasor based signal simulation approach for interferometers based on short coherence length laser sources has been evaluated. To facilitate the use of the signal simulation, a fiber component ray tracer has since been developed that allows the creation of input files for the signal simulation environment. The software uses object oriented MATLAB code, simplifying the entry of different fiber setups and the extension of the ray tracer. Thus, a seamless way from a system description based on arbitrarily interconnected fiber components to a signal simulation for different target scenarios has been established. The ray tracer and signal simulation are being used for the evaluation of interferometer concepts incorporating delay lines to compensate for short coherence length.

  17. A solid target for SINQ based on a Pb-shot Pebble-bed

    International Nuclear Information System (INIS)

    Atchison, F.; Heidenreich, G.

    1991-01-01

    Preliminary results from scoping calculations examining the possibilities of implementing a Pebble-bed of Pb-shot as a target for SINQ are presented. The primary design objects are set out and estimates of heating and activation given. Cooling circuit parameters are discussed and estimates for operating conditions presented. A short discussion of problems associated with a realisation is included. (author)

  18. Impact of Competency-Based and Target-Oriented Training on Employee Performance: A Case Study

    Science.gov (United States)

    Arslan, Ridvan; Uzaslan, N. Tufan

    2017-01-01

    Some firms have applied different in-house training models to keep up with new technological innovations in their specific fields. This study investigated how a target-oriented in-house training programme should be developed and how it should be evaluated for effectiveness. The aim of the study was to develop, implement and evaluate a…

  19. Application of time-reversal-based processing techniques to enhance detection of GPR targets

    Science.gov (United States)

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

    2017-11-01

    In this paper we analyze the performance of time-reversal (TR) techniques in conjunction with various Ground Penetrating Radar (GPR) pre-processing methods aimed at improving detection of subsurface targets. TR techniques were first developed for ultrasound applications and, by exploiting the invariance of the wave equation under time reversal, can yield features such as superresolution and statistical stability. The TR method was examined here using both synthetic and actual GPR field data under four different pre-processing strategies on the raw data, namely: mean background removal, eigenvalue background removal, a sliding-window space-frequency technique, and a noise-robust spatial differentiator along the scan direction. Depending on the acquisition mode, it was possible to determine with good precision the position and depth of the studied targets as well as, in some cases, to differentiate the targets from nearby clutter such as localized geological anomalies. The proposed methodology has the potential to be useful when applied to GPR data for the detection of buried targets.

  20. In-silico Metabolome Target Analysis Towards PanC-based Antimycobacterial Agent Discovery.

    Science.gov (United States)

    Khoshkholgh-Sima, Baharak; Sardari, Soroush; Izadi Mobarakeh, Jalal; Khavari-Nejad, Ramezan Ali

    2015-01-01

    Mycobacterium tuberculosis, the main cause of tuberculosis (TB), has still remained a global health crisis especially in developing countries. Tuberculosis treatment is a laborious and lengthy process with high risk of noncompliance, cytotoxicity adverse events and drug resistance in patient. Recently, there has been an alarming rise of drug resistant in TB. In this regard, it is an unmet need to develop novel antitubercular medicines that target new or more effective biochemical pathways to prevent drug resistant Mycobacterium. Integrated study of metabolic pathways through in-silico approach played a key role in antimycobacterial design process in this study. Our results suggest that pantothenate synthetase (PanC), anthranilate phosphoribosyl transferase (TrpD) and 3-isopropylmalate dehydratase (LeuD) might be appropriate drug targets. In the next step, in-silico ligand analysis was used for more detailed study of chemical tractability of targets. This was helpful to identify pantothenate synthetase (PanC, Rv3602c) as the best target for antimycobacterial design procedure. Virtual library screening on the best ligand of PanC was then performed for inhibitory ligand design. At the end, five chemical intermediates showed significant inhibition of Mycobacterium bovis with good selectivity indices (SI) ≥10 according to Tuberculosis Antimicrobial Acquisition & Coordinating Facility of US criteria for antimycobacterial screening programs.

  1. Preparation and in vitro evaluation of polymer conjugates actively targeted using RGD-based peptides

    Czech Academy of Sciences Publication Activity Database

    Böhmová, Eliška; Pola, Robert; Pechar, Michal; Janoušková, Olga; Zuska, K.; Etrych, Tomáš

    2017-01-01

    Roč. 6, 4 (Suppl) (2017), s. 91 ISSN 2325-9604. [International Conference and Exhibition on Nanomedicine and Drug Delivery. 29.05.2017-31.05.2017, Osaka] R&D Projects: GA ČR(CZ) GA16-17207S Institutional support: RVO:61389013 Keywords : polymer drug carriers * HPMA * peptide tumor targeting Subject RIV: CD - Macromolecular Chemistry

  2. The CERN target and horn concept for a neutrino factory based on muon beams

    CERN Document Server

    Ravn, H L

    2003-01-01

    A conceptual design is presented for a high-power pion production target and collection system, which is suggested to be used as source for the proposed CERN muon-neutrino factory. A relatively low-energy proton beam of 2.2 GeV which is pulsed at 50 Hz with similar to 10**1**4 ppp and 4 MW average power has been chosen as driver. The deleterious effects of the up to 1 kW/g power densities deposited in the target and its surroundings by the proton beam are a major technical challenge since it seriously limits the lifetime of all solid components. A target, which consists of a free surface mercury- jet with a high axial velocity, allows efficiently to carry the heat away from the production region without need for beam windows. The secondary pions are collected and injected into the pion decay channel by means of a magnetic horn. This horn which has to surround the Hg-jet target is known to be very radiation resistant as well as light and easy to exchange. The suggested mechanical layout and technical parameter...

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

    DEFF Research Database (Denmark)

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

    2017-01-01

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

  4. Targeted in vivo delivery of nucleic acids by lipid-based carriers

    NARCIS (Netherlands)

    Bartsch, Martin

    2005-01-01

    This thesis focuses on the development of targeted liposomal carriers for the delivery of antisense ODN and DNA in vivo to various cell types in the liver. The power of the antisense approach as well as of DNA transfection has been thoroughly characterized in numerous in vitro studies. However,

  5. Optimizing targeted vaccination across cyber-physical networks: an empirically based mathematical simulation study.

    Science.gov (United States)

    Mones, Enys; Stopczynski, Arkadiusz; Pentland, Alex 'Sandy'; Hupert, Nathaniel; Lehmann, Sune

    2018-01-01

    Targeted vaccination, whether to minimize the forward transmission of infectious diseases or their clinical impact, is one of the 'holy grails' of modern infectious disease outbreak response, yet it is difficult to achieve in practice due to the challenge of identifying optimal targets in real time. If interruption of disease transmission is the goal, targeting requires knowledge of underlying person-to-person contact networks. Digital communication networks may reflect not only virtual but also physical interactions that could result in disease transmission, but the precise overlap between these cyber and physical networks has never been empirically explored in real-life settings. Here, we study the digital communication activity of more than 500 individuals along with their person-to-person contacts at a 5-min temporal resolution. We then simulate different disease transmission scenarios on the person-to-person physical contact network to determine whether cyber communication networks can be harnessed to advance the goal of targeted vaccination for a disease spreading on the network of physical proximity. We show that individuals selected on the basis of their closeness centrality within cyber networks (what we call 'cyber-directed vaccination') can enhance vaccination campaigns against diseases with short-range (but not full-range) modes of transmission. © 2018 The Author(s).

  6. Group Targets Tracking Using Multiple Models GGIW-CPHD Based on Best-Fitting Gaussian Approximation and Strong Tracking Filter

    Directory of Open Access Journals (Sweden)

    Yun Wang

    2016-01-01

    Full Text Available Gamma Gaussian inverse Wishart cardinalized probability hypothesis density (GGIW-CPHD algorithm was always used to track group targets in the presence of cluttered measurements and missing detections. A multiple models GGIW-CPHD algorithm based on best-fitting Gaussian approximation method (BFG and strong tracking filter (STF is proposed aiming at the defect that the tracking error of GGIW-CPHD algorithm will increase when the group targets are maneuvering. The best-fitting Gaussian approximation method is proposed to implement the fusion of multiple models using the strong tracking filter to correct the predicted covariance matrix of the GGIW component. The corresponding likelihood functions are deduced to update the probability of multiple tracking models. From the simulation results we can see that the proposed tracking algorithm MM-GGIW-CPHD can effectively deal with the combination/spawning of groups and the tracking error of group targets in the maneuvering stage is decreased.

  7. Accelerating Genome Editing in CHO Cells Using CRISPR Cas9 and CRISPy, a Web-Based Target Finding Tool

    DEFF Research Database (Denmark)

    Ronda, Carlotta; Pedersen, Lasse Ebdrup; Hansen, Henning Gram

    2014-01-01

    of the CRISPR Cas9 technology in CHO cells by generating site-specific gene disruptions in COSMC and FUT8, both of which encode proteins involved in glycosylation. The tested single guide RNAs (sgRNAs) created an indel frequency up to 47.3% in COSMC, while an indel frequency up to 99.7% in FUT8 was achieved...... mutations at the target sites, with a strong preference for single base indels. Finally, we have developed a user-friendly bioinformatics tool, named “CRISPy” for rapid identification of sgRNA target sequences in the CHO-K1 genome. The CRISPy tool identified 1,970,449 CRISPR targets divided into 27...

  8. Identification of Thioredoxin Disulfide Targets Using a Quantitative Proteomics Approach Based on Isotope-Coded Affinity Tags

    DEFF Research Database (Denmark)

    Hägglund, Per; Bunkenborg, Jakob; Maeda, Kenji

    2008-01-01

    Thioredoxin (Trx) is a ubiquitous protein disulfide reductase involved in a wide range of cellular redox processes. A large number of putative target proteins have been identified using proteomics approaches, but insight into target specificity at the molecular level is lacking since the reactivity......, protein extract of embryos from germinated barley seeds was treated +/- Trx, and thiols released from target protein disulfides were irreversibly blocked with iodoacetamide. The remaining cysteine residues in the Trx-treated and the control (-Trx) samples were then chemically reduced and labeled...... with the "light" (C-12) and "heavy" (C-13) ICAT reagent, respectively. The extent of Trx-mediated reduction was thus quantified for individual cysteine residues based on ratios of tryptic peptides labeled with the two ICAT reagents as measured by liquid chromatography coupled with mass spectrometry (LC...

  9. Universal, colorimetric microRNA detection strategy based on target-catalyzed toehold-mediated strand displacement reaction

    Science.gov (United States)

    Park, Yeonkyung; Lee, Chang Yeol; Kang, Shinyoung; Kim, Hansol; Park, Ki Soo; Park, Hyun Gyu

    2018-02-01

    In this work, we developed a novel, label-free, and enzyme-free strategy for the colorimetric detection of microRNA (miRNA), which relies on a target-catalyzed toehold-mediated strand displacement (TMSD) reaction. The system employs a detection probe that specifically binds to the target miRNA and sequentially releases a catalyst strand (CS) intended to trigger the subsequent TMSD reaction. Thus, the presence of target miRNA releases the CS that mediates the formation of an active G-quadruplex DNAzyme which is initially caged and inactivated by a blocker strand. In addition, a fuel strand that is supplemented for the recycling of the CS promotes another TMSD reaction, consequently generating a large number of active G-quadruplex DNAzymes. As a result, a distinct colorimetric signal is produced by the ABTS oxidation promoted by the peroxidase mimicking activity of the released G-quadruplex DNAzymes. Based on this novel strategy, we successfully detected miR-141, a promising biomarker for human prostate cancer, with high selectivity. The diagnostic capability of this system was also demonstrated by reliably determining target miR-141 in human serum, showing its great potential towards real clinical applications. Importantly, the proposed approach is composed of separate target recognition and signal transduction modules. Thus, it could be extended to analyze different target miRNAs by simply redesigning the detection probe while keeping the same signal transduction module as a universal signal amplification unit, which was successfully demonstrated by analyzing another target miRNA, let-7d.

  10. An indirect adaptive neural control of a visual-based quadrotor robot for pursuing a moving target.

    Science.gov (United States)

    Shirzadeh, Masoud; Amirkhani, Abdollah; Jalali, Aliakbar; Mosavi, Mohammad R

    2015-11-01

    This paper aims to use a visual-based control mechanism to control a quadrotor type aerial robot which is in pursuit of a moving target. The nonlinear nature of a quadrotor, on the one hand, and the difficulty of obtaining an exact model for it, on the other hand, constitute two serious challenges in designing a controller for this UAV. A potential solution for such problems is the use of intelligent control methods such as those that rely on artificial neural networks and other similar approaches. In addition to the two mentioned problems, another problem that emerges due to the moving nature of a target is the uncertainty that exists in the target image. By employing an artificial neural network with a Radial Basis Function (RBF) an indirect adaptive neural controller has been designed for a quadrotor robot in search of a moving target. The results of the simulation for different paths show that the quadrotor has efficiently tracked the moving target. Copyright © 2015 ISA. Published by Elsevier Ltd. All rights reserved.

  11. Targeting HIV Prevention Based on Molecular Epidemiology Among Deeply Sampled Subnetworks of Men Who Have Sex With Men.

    Science.gov (United States)

    Wang, Xicheng; Wu, Yasong; Mao, Lin; Xia, Wei; Zhang, Weiwei; Dai, Lili; Mehta, Sanjay R; Wertheim, Joel O; Dong, Xingqi; Zhang, Tong; Wu, Hao; Smith, Davey M

    2015-11-01

    Molecular epidemiology can be useful in identifying clusters of human immunodeficiency virus (HIV) transmission that can be targeted for prevention. Regular screening of 2000 men who have sex with men (MSM) in Beijing, China, for HIV infection every 2 months identified 179 primary infections (2007-2010). HIV-1 pol sequences were obtained and used to infer the transmission network and identify transmitted drug resistance (TDR) among these individuals. We evaluated the use of clinical and network information to target prevention efforts. Prevention efficiency was calculated as the number of infections saved per number of interventions. This cohort was infected with HIV-1 subtype B (28%), circulating recombinant form (CRF)_01 AE (53%), and CRF_07 BC (16%). The overall rate of TDR was low (5%), but the rate of clustering was high (64%), suggesting deep sampling of the subnetwork. Provision of a theoretically high-efficacy intervention like antiretroviral therapy to all participants had a prevention efficiency of 23%. The efficiency of targeting prevention based on lower CD4 counts (100 000 copies/mL and >50 000 copies/mL) was between 10% and 18%. The efficiency of targeting prevention based on number of network connections was much higher (30%-42%). For example, treating the 33 participants with ≥5 connections in 2009 would have theoretically prevented 14 infections in 2010 (42% prevention efficiency). Regular HIV testing of MSM in Beijing can deeply sample the local transmission subnetwork, and targeting prevention efforts based on network connectivity may be an efficient way to deliver prevention interventions. Published by Oxford University Press on behalf of the Infectious Diseases Society of America 2015. This work is written by (a) US Government employee(s) and is in the public domain in the US.

  12. Identifying Candidate Targets of Immune Responses in Zika Virus Based on Homology to Epitopes in Other Flavivirus Species.

    Science.gov (United States)

    Xu, Xiaojun; Vaughan, Kerrie; Weiskopf, Daniela; Grifoni, Alba; Diamond, Michael S; Sette, Alessandro; Peters, Bjoern

    2016-11-15

    The current outbreak of Zika virus has resulted in a massive effort to accelerate the development of ZIKV-specific diagnostics and vaccines. These efforts would benefit greatly from the definition of the specific epitope targets of immune responses in ZIKV, but given the relatively recent emergence of ZIKV as a pandemic threat, few such data are available. We used a large body of epitope data for other Flaviviruses that was available from the IEDB for a comparative analysis against the ZIKV proteome in order to project targets of immune responses in ZIKV. We found a significant level of overlap between known antigenic sites from other Flavivirus proteins with residues on the ZIKV polyprotein. The E and NS1 proteins shared functional antibody epitope sites, whereas regions of T cell reactivity were conserved within NS3 and NS5 for ZIKV.  Discussion: Our epitope based analysis provides guidance for which regions of the ZIKV polyprotein are most likely unique targets of ZIKV-specific antibodies, and which targets in ZIKV are most likely to be cross-reactive with other Flavivirus species. These data may therefore provide insights for the development of antibody- and T cell-based ZIKV-specific diagnostics, therapeutics and prophylaxis.

  13. Molecular-target-based anticancer photosensitizer: synthesis and in vitro photodynamic activity of erlotinib-zinc(II) phthalocyanine conjugates.

    Science.gov (United States)

    Zhang, Feng-Ling; Huang, Qi; Liu, Jian-Yong; Huang, Ming-Dong; Xue, Jin-Ping

    2015-02-01

    Targeted photodynamic therapy is a new promising therapeutic strategy to overcome growing problems in contemporary medicine, such as drug toxicity and drug resistance. A series of erlotinib-zinc(II) phthalocyanine conjugates were designed and synthesized. Compared with unsubstituted zinc(II) phthalocyanine, these conjugates can successfully target EGFR-overexpressing cancer cells owing to the presence of the small molecular-target-based anticancer agent erlotinib. All conjugates were found to be essentially non-cytotoxic in the absence of light (up to 50 μM), but upon illumination, they show significantly high photo-cytotoxicity toward HepG2 cells, with IC50 values as low as 9.61-91.77 nM under a rather low light dose (λ=670 nm, 1.5 J cm(-2) ). Structure-activity relationships for these conjugates were assessed by determining their photophysical/photochemical properties, cellular uptake, and in vitro photodynamic activities. The results show that these conjugates are highly promising antitumor agents for molecular-target-based photodynamic therapy. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  14. Design of a modular protein-based MRI contrast agent for targeted application.

    Directory of Open Access Journals (Sweden)

    Daniel Grum

    Full Text Available Magnetic resonance imaging (MRI offers a non-radioactive alternative for the non-invasive detection of tumours. Low molecular weight MRI contrast agents currently in clinical use suffer either from a lack of specificity for tumour tissue or from low relaxivity and thus low contrast amplification. In this study, we present the newly designed two domain fusion protein Zarvin, which is able to bind to therapeutic IgG antibodies suitable for targeting, while facilitating contrast enhancement through high affinity binding sites for Gd(3+. We show that the Zarvin fold is stable under serum conditions, specifically targets a cancer cell-line when bound to the Cetuximab IgG, and allows for imaging with high relaxivity, a property that would be advantageous for the detection of small tumours and metastases at 1.5 or 3 T.

  15. Targeting Mycobacterium tuberculosis nucleoid-associated protein HU with structure-based inhibitors

    Science.gov (United States)

    Bhowmick, Tuhin; Ghosh, Soumitra; Dixit, Karuna; Ganesan, Varsha; Ramagopal, Udupi A.; Dey, Debayan; Sarma, Siddhartha P.; Ramakumar, Suryanarayanarao; Nagaraja, Valakunja

    2014-06-01

    The nucleoid-associated protein HU plays an important role in maintenance of chromosomal architecture and in global regulation of DNA transactions in bacteria. Although HU is essential for growth in Mycobacterium tuberculosis (Mtb), there have been no reported attempts to perturb HU function with small molecules. Here we report the crystal structure of the N-terminal domain of HU from Mtb. We identify a core region within the HU-DNA interface that can be targeted using stilbene derivatives. These small molecules specifically inhibit HU-DNA binding, disrupt nucleoid architecture and reduce Mtb growth. The stilbene inhibitors induce gene expression changes in Mtb that resemble those induced by HU deficiency. Our results indicate that HU is a potential target for the development of therapies against tuberculosis.

  16. Targeted lipid based drug conjugates: a novel strategy for drug delivery.

    Science.gov (United States)

    Vadlapudi, Aswani Dutt; Vadlapatla, Ramya Krishna; Kwatra, Deep; Earla, Ravinder; Samanta, Swapan K; Pal, Dhananjay; Mitra, Ashim K

    2012-09-15

    A majority of studies involving prodrugs are directed to overcome low bioavailability of the parent drug. The aim of this study is to increase the bioavailability of acyclovir (ACV) by designing a novel prodrug delivery system which is more lipophilic, and at the same time site specific. In this study, a lipid raft has been conjugated to the parent drug molecule to impart lipophilicity. Simultaneously a targeting moiety that can be recognized by a specific transporter/receptor in the cell membrane has also been tethered to the other terminal of lipid raft. Targeted lipid prodrugs i.e., biotin-ricinoleicacid-acyclovir (B-R-ACV) and biotin-12hydroxystearicacid-acyclovir (B-12HS-ACV) were synthesized with ricinoleicacid and 12hydroxystearicacid as the lipophilic rafts and biotin as the targeting moiety. Biotin-ACV (B-ACV), ricinoleicacid-ACV (R-ACV) and 12hydroxystearicacid-ACV (12HS-ACV) were also synthesized to delineate the individual effects of the targeting and the lipid moieties. Cellular accumulation studies were performed in confluent MDCK-MDR1 and Caco-2 cells. The targeted lipid prodrugs B-R-ACV and B-12HS-ACV exhibited much higher cellular accumulation than B-ACV, R-ACV and 12HS-ACV in both cell lines. This result indicates that both the targeting and the lipid moiety act synergistically toward cellular uptake. The biotin conjugated prodrugs caused a decrease in the uptake of [(3)H] biotin suggesting the role of sodium dependent multivitamin transporter (SMVT) in uptake. The affinity of these targeted lipid prodrugs toward SMVT was studied in MDCK-MDR1 cells. Both the targeted lipid prodrugs B-R-ACV (20.25 ± 1.74 μM) and B-12HS-ACV (23.99 ± 3.20 μM) demonstrated higher affinity towards SMVT than B-ACV (30.90 ± 4.19 μM). Further, dose dependent studies revealed a concentration dependent inhibitory effect on [(3)H] biotin uptake in the presence of biotinylated prodrugs. Transepithelial transport studies showed lowering of [(3)H] biotin permeability in

  17. Optimizing targeted vaccination across cyber-physical networks: an empirically based mathematical simulation study

    DEFF Research Database (Denmark)

    Mones, Enys; Stopczynski, Arkadiusz; Pentland, Alex 'Sandy'

    2018-01-01

    . If interruption of disease transmission is the goal, targeting requires knowledge of underlying person-to-person contact networks. Digital communication networks may reflect not only virtual but also physical interactions that could result in disease transmission, but the precise overlap between these cyber......-to-person physical contact network to determine whether cyber communication networks can be harnessed to advance the goal of targeted vaccination for a disease spreading on the network of physical proximity. We show that individuals selected on the basis of their closeness centrality within cyber networks (what we...... and physical networks has never been empirically explored in real-life settings. Here, we study the digital communication activity of more than 500 individuals along with their person-to-person contacts at a 5-min temporal resolution. We then simulate different disease transmission scenarios on the person...

  18. Estimating Target Heights Based on the Earth Curvature Model and Micromultipath Effect in Skywave OTH Radar

    Directory of Open Access Journals (Sweden)

    Hou Chengyu

    2014-01-01

    Full Text Available Skywave over-the-horizon (OTH radar systems have important long-range strategic warning values. They exploit skywave propagation reflection of high frequency signals from the ionosphere, which provides the ultra-long-range surveillance capabilities to detect and track maneuvering targets. Current OTH radar systems are capable of localizing targets in range and azimuth but are unable to achieve reliable instantaneous altitude estimation. Most existing height measurement methods of skywave OTH radar systems have taken advantage of the micromultipath effect and been considered in the flat earth model. However, the flat earth model is not proper since large error is inevitable, when the detection range is over one thousand kilometers. In order to avoid the error caused by the flat earth model, in this paper, an earth curvature model is introduced into OTH radar altimetry methods. The simulation results show that application of the earth curvature model can effectively reduce the estimation error.

  19. Self-assembled peptide-based nanostructures: Smart nanomaterials toward targeted drug delivery.

    Science.gov (United States)

    Habibi, Neda; Kamaly, Nazila; Memic, Adnan; Shafiee, Hadi

    2016-02-01

    Self-assembly of peptides can yield an array of well-defined nanostructures that are highly attractive nanomaterials for many biomedical applications such as drug delivery. Some of the advantages of self-assembled peptide nanostructures over other delivery platforms include their chemical diversity, biocompatibility, high loading capacity for both hydrophobic and hydrophilic drugs, and their ability to target molecular recognition sites. Furthermore, these self-assembled nanostructures could be designed with novel peptide motifs, making them stimuli-responsive and achieving triggered drug delivery at disease sites. The goal of this work is to present a comprehensive review of the most recent studies on self-assembled peptides with a focus on their "smart" activity for formation of targeted and responsive drug-delivery carriers.

  20. Target Matching Recognition for Satellite Images Based on the Improved FREAK Algorithm

    Directory of Open Access Journals (Sweden)

    Yantong Chen

    2016-01-01

    Full Text Available Satellite remote sensing image target matching recognition exhibits poor robustness and accuracy because of the unfit feature extractor and large data quantity. To address this problem, we propose a new feature extraction algorithm for fast target matching recognition that comprises an improved feature from accelerated segment test (FAST feature detector and a binary fast retina key point (FREAK feature descriptor. To improve robustness, we extend the FAST feature detector by applying scale space theory and then transform the feature vector acquired by the FREAK descriptor from decimal into binary. We reduce the quantity of data in the computer and improve matching accuracy by using the binary space. Simulation test results show that our algorithm outperforms other relevant methods in terms of robustness and accuracy.

  1. A role for fragment-based drug design in developing novel lead compounds for central nervous system targets

    Directory of Open Access Journals (Sweden)

    Michael J. Wasko

    2015-09-01

    Full Text Available Hundreds of millions of U.S. dollars are invested in the research and development of a single drug. Lead compound development is an area ripe for new design strategies. Therapeutic lead candidates have been traditionally found using high-throughput in vitro pharmacologic screening, a costly method for assaying thousands of compounds. This approach has recently been augmented by virtual screening, which employs computer models of the target protein to narrow the search for possible leads. A variant of virtual screening is fragment-based drug design, an emerging in silico lead discovery method that introduces low molecular weight fragments, rather than intact compounds, into the binding pocket of the receptor model. These fragments serve as starting points for growing the lead candidate. Current efforts in virtual fragment-based drug desig