Sample records for target experimental systems

  1. Monitoring System for the Gold Target by Radiation Detectors in Hadron Experimental Facility at J-PARC

    NASA Astrophysics Data System (ADS)

    Muto, Ryotaro; Agari, Keizo; Aoki, Kazuya; Bessho, Kotaro; Hagiwara, Masayuki; Hirose, Erina; Ieiri, Masaharu; Iwasaki, Ruri; Katoh, Yohji; Kitagawa, Jun-ichi; Minakawa, Michifumi; Morino, Yuhei; Saito, Kiwamu; Sato, Yoshinori; Sawada, Shin'ya; Shirakabe, Yoshihisa; Suzuki, Yoshihiro; Takahashi, Hitoshi; Tanaka, Kazuhiro; Toyoda, Akihisa; Watanabe, Hiroaki; Yamanoi, Yutaka

    2017-09-01

    At the Hadron Experimental Facility in J-PARC, we inject a 30-GeV proton beam into a gold target to produce secondary particle beams required for various particle and nuclear physics experiments. The gold target is placed in a hermetic chamber, and helium gas is circulated in the chamber to monitor the soundness of the target. The radioactivity in helium gas is continuously monitored by gamma-ray detectors such as a germanium detector and a NaI(Tl) detector. Beam operations with those target-monitoring systems were successfully performed from April to June and October to December 2015, and from May to June 2016. In this paper, the details of the helium gas circulation system and gamma-ray detectors and the analysis results of the obtained gamma-ray spectra are reported.

  2. Quantitative targeting maps based on experimental investigations for a branched tube model in magnetic drug targeting

    NASA Astrophysics Data System (ADS)

    Gitter, K.; Odenbach, S.

    2011-12-01

    Magnetic drug targeting (MDT), because of its high targeting efficiency, is a promising approach for tumour treatment. Unwanted side effects are considerably reduced, since the nanoparticles are concentrated within the target region due to the influence of a magnetic field. Nevertheless, understanding the transport phenomena of nanoparticles in an artery system is still challenging. This work presents experimental results for a branched tube model. Quantitative results describe, for example, the net amount of nanoparticles that are targeted towards the chosen region due to the influence of a magnetic field. As a result of measurements, novel drug targeting maps, combining, e.g. the magnetic volume force, the position of the magnet and the net amount of targeted nanoparticles, are presented. The targeting maps are valuable for evaluation and comparison of setups and are also helpful for the design and the optimisation of a magnet system with an appropriate strength and distribution of the field gradient. The maps indicate the danger of accretion within the tube and also show the promising result of magnetic drug targeting that up to 97% of the nanoparticles were successfully targeted.

  3. Experimental Drug Metarrestin Targets Metastatic Tumors

    Cancer.gov

    An experimental drug called metarrestin appears to selectively target tumors that have spread to other parts of the body. As this Cancer Currents blog post reports, the drug shrank metastatic tumors and extended survival in in mouse models of pancreatic cancer.

  4. Active Multimodal Sensor System for Target Recognition and Tracking

    PubMed Central

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

    2017-01-01

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

  5. New Wnt/β-catenin target genes promote experimental metastasis and migration of colorectal cancer cells through different signals.

    PubMed

    Qi, Jingjing; Yu, Yong; Akilli Öztürk, Özlem; Holland, Jane D; Besser, Daniel; Fritzmann, Johannes; Wulf-Goldenberg, Annika; Eckert, Klaus; Fichtner, Iduna; Birchmeier, Walter

    2016-10-01

    We have previously identified a 115-gene signature that characterises the metastatic potential of human primary colon cancers. The signature included the canonical Wnt target gene BAMBI, which promoted experimental metastasis in mice. Here, we identified three new direct Wnt target genes from the signature, and studied their functions in epithelial-mesenchymal transition (EMT), cell migration and experimental metastasis. We examined experimental liver metastases following injection of selected tumour cells into spleens of NOD/SCID mice. Molecular and cellular techniques were used to identify direct transcription target genes of Wnt/β-catenin signals. Microarray analyses and experiments that interfered with cell migration through inhibitors were performed to characterise downstream signalling systems. Three new genes from the colorectal cancer (CRC) metastasis signature, BOP1, CKS2 and NFIL3, were identified as direct transcription targets of β-catenin/TCF4. Overexpression and knocking down of these genes in CRC cells promoted and inhibited, respectively, experimental metastasis in mice, EMT and cell motility in culture. Cell migration was repressed by interfering with distinct signalling systems through inhibitors of PI3K, JNK, p38 mitogen-activated protein kinase and/or mTOR. Gene expression profiling identified a series of migration-promoting genes, which were induced by BOP1, CKS2 and NFIL3, and could be repressed by inhibitors that are specific to these pathways. We identified new direct Wnt/β-catenin target genes, BOP1, CKS2 and NFIL3, which induced EMT, cell migration and experimental metastasis of CRC cells. These genes crosstalk with different downstream signalling systems, and activate migration-promoting genes. These pathways and downstream genes may serve as therapeutic targets in the treatment of CRC metastasis. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

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

    PubMed

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

    2017-11-27

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

  7. Experimental and theoretical studies of implant assisted magnetic drug targeting

    NASA Astrophysics Data System (ADS)

    Aviles, Misael O.

    One way to achieve drug targeting in the body is to incorporate magnetic nanoparticles into drug carriers and then retain them at the site using an externally applied magnetic field. This process is referred to as magnetic drug targeting (MDT). However, the main limitation of MDT is that an externally applied magnetic field alone may not be able to retain a sufficient number of magnetic drug carrier particles (MDCPs) to justify its use. Such a limitation might not exist when high gradient magnetic separation (HGMS) principles are applied to assist MDT by means of ferromagnetic implants. It was hypothesized that an Implant Assisted -- MDT (IA-MDT) system would increase the retention of the MDCPs at a target site where an implant had been previously located, since the magnetic forces are produced internally. With this in mind, the overall objective of this work was to demonstrate the feasibility of an IA-MDT system through mathematical modeling and in vitro experimentation. The mathematical models were developed and used to demonstrate the behavior and limitations of IA-MDT, and the in vitro experiments were designed and used to validate the models and to further elucidate the important parameters that affect the performance of the system. IA-MDT was studied with three plausible implants, ferromagnetic stents, seed particles, and wires. All implants were studied theoretically and experimentally using flow through systems with polymer particles containing magnetite nanoparticles as MDCPs. In the stent studies, a wire coil or mesh was simply placed in a flow field and the capture of the MDCPs was studied. In the other cases, a porous polymer matrix was used as a surrogate capillary tissue scaffold to study the capture of the MDCPs using wires or particle seeds as the implant, with the seeds either fixed within the polymer matrix or captured prior to capturing the MDCPs. An in vitro heart tissue perfusion model was also used to study the use of stents. In general, all

  8. Mechanical design of experimental apparatus for FIREX cryo-target cooling

    NASA Astrophysics Data System (ADS)

    Iwamoto, A.; Norimatsu, T.; Nakai, M.; Sakagami, H.; Fujioka, S.; Shiraga, H.; Azechi, H.

    2016-05-01

    Mechanical design of an experimental apparatus for FIREX cryo-target cooling is described. Gaseous helium (GHe) sealing system at a cryogenic environment is an important issue for laser fusion experiments. The dedicated loading system was designed for a metal gasket. We take U-TIGHTSEAL® (Usui Kokusai Sangyo Kaisha. Ltd.) with an indium plated copper jacket as an example. According to its specification, a linear load of 110 N/m along its circumference is the optimum compression; however a lower load would still maintain helium (He) leak below the required level. Its sealing performance was investigated systematically. Our system demanded 27 N/mm of the load to keep He leak tightness in a cryogenic environment. Once leak tightness was obtained, it could be reduced to 9.5 N/mm.

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

    PubMed

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

    2012-04-05

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

  10. An underwater ranging system based on photoacoustic effect occurring on target surface

    NASA Astrophysics Data System (ADS)

    Ni, Kai; Hu, Kai; Li, Xinghui; Wang, Lidai; Zhou, Qian; Wang, Xiaohao

    2016-11-01

    In this paper, an underwater ranging system based on photoacoustic effect occurring on target surface is proposed. In this proposal, laser pulse generated by blue-green laser is directly incident on target surface, where the photoacoustic effect occurs and a sound source is formed. And then the sound wave which is also called photoacoustic signal is received by the ultrasonic receiver after passing through water. According to the time delay between transmitting laser and receiving photoacoustic signal, and sound velocity in water, the distance between the target and the ultrasonic receiver can be calculated. Differing from underwater range finding by only laser, this approach can avoid backscattering of laser beam, so easier to implement. Experimental system according to this principle has been constructed to verify the feasibility of this technology. The experimental results showed that a ranging accuracy of 1 mm can be effectively achieved when the target is close to the ultrasonic receiver.

  11. Advances in Bone-targeted Drug Delivery Systems for Neoadjuvant Chemotherapy for Osteosarcoma.

    PubMed

    Li, Cheng-Jun; Liu, Xiao-Zhou; Zhang, Lei; Chen, Long-Bang; Shi, Xin; Wu, Su-Jia; Zhao, Jian-Ning

    2016-05-01

    Targeted therapy for osteosarcoma includes organ, cell and molecular biological targeting; of these, organ targeting is the most mature. Bone-targeted drug delivery systems are used to concentrate chemotherapeutic drugs in bone tissues, thus potentially resolving the problem of reaching the desired foci and minimizing the toxicity and adverse effects of neoadjuvant chemotherapy. Some progress has been made in bone-targeted drug delivery systems for treatment of osteosarcoma; however, most are still at an experimental stage and there is a long transitional period to clinical application. Therefore, determining how to combine new, polymolecular and multi-pathway targets is an important research aspect of designing new bone-targeted drug delivery systems in future studies. The purpose of this article was to review the status of research on targeted therapy for osteosarcoma and to summarize the progress made thus far in developing bone-targeted drug delivery systems for neoadjuvant chemotherapy for osteosarcoma with the aim of providing new ideas for highly effective therapeutic protocols with low toxicity for patients with osteosarcoma. © 2016 Chinese Orthopaedic Association and John Wiley & Sons Australia, Ltd.

  12. Targeting Accuracy, Procedure Times and User Experience of 240 Experimental MRI Biopsies Guided by a Clinical Add-On Navigation System.

    PubMed

    Busse, Harald; Riedel, Tim; Garnov, Nikita; Thörmer, Gregor; Kahn, Thomas; Moche, Michael

    2015-01-01

    MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively ("in-and-out") in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators. Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators - attending (AR) and resident radiologists (RR) as well as medical students (MS) - performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm). Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0). Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min:sec) differed significantly (p<0.01). Mean overall rating was 4.2. The average operator would use the system again (4.8) and stated that the outcome justifies the extra effort (4.4). Lowest agreement was reported for the robustness against external perturbations (2.8). The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore) MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between groups with different expertise there were

  13. Targeting Accuracy, Procedure Times and User Experience of 240 Experimental MRI Biopsies Guided by a Clinical Add-On Navigation System

    PubMed Central

    Busse, Harald; Riedel, Tim; Garnov, Nikita; Thörmer, Gregor; Kahn, Thomas; Moche, Michael

    2015-01-01

    Objectives MRI is of great clinical utility for the guidance of special diagnostic and therapeutic interventions. The majority of such procedures are performed iteratively ("in-and-out") in standard, closed-bore MRI systems with control imaging inside the bore and needle adjustments outside the bore. The fundamental limitations of such an approach have led to the development of various assistance techniques, from simple guidance tools to advanced navigation systems. The purpose of this work was to thoroughly assess the targeting accuracy, workflow and usability of a clinical add-on navigation solution on 240 simulated biopsies by different medical operators. Methods Navigation relied on a virtual 3D MRI scene with real-time overlay of the optically tracked biopsy needle. Smart reference markers on a freely adjustable arm ensured proper registration. Twenty-four operators – attending (AR) and resident radiologists (RR) as well as medical students (MS) – performed well-controlled biopsies of 10 embedded model targets (mean diameter: 8.5 mm, insertion depths: 17-76 mm). Targeting accuracy, procedure times and 13 Likert scores on system performance were determined (strong agreement: 5.0). Results Differences in diagnostic success rates (AR: 93%, RR: 88%, MS: 81%) were not significant. In contrast, between-group differences in biopsy times (AR: 4:15, RR: 4:40, MS: 5:06 min:sec) differed significantly (p<0.01). Mean overall rating was 4.2. The average operator would use the system again (4.8) and stated that the outcome justifies the extra effort (4.4). Lowest agreement was reported for the robustness against external perturbations (2.8). Conclusions The described combination of optical tracking technology with an automatic MRI registration appears to be sufficiently accurate for instrument guidance in a standard (closed-bore) MRI environment. High targeting accuracy and usability was demonstrated on a relatively large number of procedures and operators. Between

  14. Computational-experimental approach to drug-target interaction mapping: A case study on kinase inhibitors

    PubMed Central

    Ravikumar, Balaguru; Parri, Elina; Timonen, Sanna; Airola, Antti; Wennerberg, Krister

    2017-01-01

    Due to relatively high costs and labor required for experimental profiling of the full target space of chemical compounds, various machine learning models have been proposed as cost-effective means to advance this process in terms of predicting the most potent compound-target interactions for subsequent verification. However, most of the model predictions lack direct experimental validation in the laboratory, making their practical benefits for drug discovery or repurposing applications largely unknown. Here, we therefore introduce and carefully test a systematic computational-experimental framework for the prediction and pre-clinical verification of drug-target interactions using a well-established kernel-based regression algorithm as the prediction model. To evaluate its performance, we first predicted unmeasured binding affinities in a large-scale kinase inhibitor profiling study, and then experimentally tested 100 compound-kinase pairs. The relatively high correlation of 0.77 (p < 0.0001) between the predicted and measured bioactivities supports the potential of the model for filling the experimental gaps in existing compound-target interaction maps. Further, we subjected the model to a more challenging task of predicting target interactions for such a new candidate drug compound that lacks prior binding profile information. As a specific case study, we used tivozanib, an investigational VEGF receptor inhibitor with currently unknown off-target profile. Among 7 kinases with high predicted affinity, we experimentally validated 4 new off-targets of tivozanib, namely the Src-family kinases FRK and FYN A, the non-receptor tyrosine kinase ABL1, and the serine/threonine kinase SLK. Our sub-sequent experimental validation protocol effectively avoids any possible information leakage between the training and validation data, and therefore enables rigorous model validation for practical applications. These results demonstrate that the kernel-based modeling approach

  15. GUEST EDITORS' INTRODUCTION: Testing inversion algorithms against experimental data: inhomogeneous targets

    NASA Astrophysics Data System (ADS)

    Belkebir, Kamal; Saillard, Marc

    2005-12-01

    formulation of the inverse problem. The latter can be viewed as a Bayesian adaptation of the contrast source method such that prior information about the contrast can be introduced in the prior law distribution, and it results in estimating the posterior mean instead of minimizing a cost functional. The accuracy of the result is thus closely linked to the prior knowledge of the contrast, making this approach well suited for non-destructive testing. J-M Geffrin, P Sabouroux and C Eyraud, Free space experimental scattering database continuation: experimental set-up and measurement precision, describe the experimental set-up used to carry out the data for the inversions. They report the modifications of the experimental system used previously in order to improve the precision of the measurements. Reliability of data is demonstrated through comparisons between measurements and computed scattered field with both fundamental polarizations. In addition, the reader interested in using the database will find the relevant information needed to perform inversions as well as the description of the targets under test. A Litman, Reconstruction by level sets of n-ary scattering obstacles, presents the reconstruction of targets using a level sets representation. It is assumed that the constitutive materials of the obstacles under test are known and the shape is retrieved. Two approaches are reported. In the first one the obstacles of different constitutive materials are represented in a single level set, while in the second approach several level sets are combined. The approaches are applied to the experimental data and compared. U Shahid, M Testorf and M A Fiddy, Minimum-phase-based inverse scattering algorithm applied to Institut Fresnel data, suggest a way of extending the use of minimum phase functions to 2D problems. In the kind of inverse problems we are concerned with, it consists of separating the contributions from the field and from the contrast in the so-called contrast source

  16. Polarized Solid State Target

    NASA Astrophysics Data System (ADS)

    Dutz, Hartmut; Goertz, Stefan; Meyer, Werner

    2017-01-01

    The polarized solid state target is an indispensable experimental tool to study single and double polarization observables at low intensity particle beams like tagged photons. It was one of the major components of the Crystal-Barrel experiment at ELSA. Besides the operation of the 'CB frozen spin target' within the experimental program of the Crystal-Barrel collaboration both collaborative groups of the D1 project, the polarized target group of the Ruhr Universität Bochum and the Bonn polarized target group, have made significant developments in the field of polarized targets within the CRC16. The Bonn polarized target group has focused its work on the development of technically challenging polarized solid target systems towards the so called '4π continuous mode polarized target' to operate them in combination with 4π-particle detection systems. In parallel, the Bochum group has developed various highly polarized deuterated target materials and high precision NMR-systems, in the meantime used for polarization experiments at CERN, JLAB and MAMI, too.

  17. Ideology and gender: observers' system justification and targets' gender as interactive predictors of citizenship expectations.

    PubMed

    Chiaburu, Dan S; Harris, T Brad; Smith, Troy A

    2014-01-01

    We integrate system justification and social role theory to explain how observers' system justification and target employees' gender interact to predict observers' expectations of targets' sportsmanship citizenship behaviors. In contrast with social role theory predictions, observers did not expect greater levels of sportsmanship from women compared to men. Yet observers expected more sportsmanship from women (a) when observers were ideologically motivated by gender-specific beliefs (gender-specific system justification; Study 1) and (b) when system justification was cued experimentally (Study 2). A heretofore-unexamined aspect, observers' ideology, modifies their expectations of sportsmanship citizenship across target genders. This has implications for system justification, social role, and organizational citizenship theoretical perspectives.

  18. Prevention of hepatocellular carcinoma: potential targets, experimental models, and clinical challenges

    PubMed Central

    Hoshida, Yujin; Fuchs, Bryan C.; Tanabe, Kenneth K.

    2013-01-01

    Chronic fibrotic liver diseases such as viral hepatitis eventually develop liver cirrhosis, which causes occurrence of hepatocellular carcinoma (HCC). Given the limited therapeutic efficacy in advanced HCC, prevention of HCC development could be an effective strategy for improving patient prognosis. However, there is still no established therapy to meet the goal. Studies have elucidated a wide variety of molecular mechanisms and signaling pathways involved in HCC development. Genetically-engineered or chemically-treated experimental models of cirrhosis and HCC have been developed and shown their potential value in investigating molecular therapeutic targets and diagnostic biomarkers for HCC prevention. In this review, we overview potential targets of prevention and currently available experimental models, and discuss strategies to translate the findings into clinical practice. PMID:22873223

  19. Study on a novel laser target detection system based on software radio technique

    NASA Astrophysics Data System (ADS)

    Song, Song; Deng, Jia-hao; Wang, Xue-tian; Gao, Zhen; Sun, Ji; Sun, Zhi-hui

    2008-12-01

    This paper presents that software radio technique is applied to laser target detection system with the pseudo-random code modulation. Based on the theory of software radio, the basic framework of the system, hardware platform, and the implementation of the software system are detailed. Also, the block diagram of the system, DSP circuit, block diagram of the pseudo-random code generator, and soft flow diagram of signal processing are designed. Experimental results have shown that the application of software radio technique provides a novel method to realize the modularization, miniaturization and intelligence of the laser target detection system, and the upgrade and improvement of the system will become simpler, more convenient, and cheaper.

  20. Nuclease Target Site Selection for Maximizing On-target Activity and Minimizing Off-target Effects in Genome Editing

    PubMed Central

    Lee, Ciaran M; Cradick, Thomas J; Fine, Eli J; Bao, Gang

    2016-01-01

    The rapid advancement in targeted genome editing using engineered nucleases such as ZFNs, TALENs, and CRISPR/Cas9 systems has resulted in a suite of powerful methods that allows researchers to target any genomic locus of interest. A complementary set of design tools has been developed to aid researchers with nuclease design, target site selection, and experimental validation. Here, we review the various tools available for target selection in designing engineered nucleases, and for quantifying nuclease activity and specificity, including web-based search tools and experimental methods. We also elucidate challenges in target selection, especially in predicting off-target effects, and discuss future directions in precision genome editing and its applications. PMID:26750397

  1. Target Highlights in CASP9: Experimental Target Structures for the Critical Assessment of Techniques for Protein Structure Prediction

    PubMed Central

    Kryshtafovych, Andriy; Moult, John; Bartual, Sergio G.; Bazan, J. Fernando; Berman, Helen; Casteel, Darren E.; Christodoulou, Evangelos; Everett, John K.; Hausmann, Jens; Heidebrecht, Tatjana; Hills, Tanya; Hui, Raymond; Hunt, John F.; Jayaraman, Seetharaman; Joachimiak, Andrzej; Kennedy, Michael A.; Kim, Choel; Lingel, Andreas; Michalska, Karolina; Montelione, Gaetano T.; Otero, José M.; Perrakis, Anastassis; Pizarro, Juan C.; van Raaij, Mark J.; Ramelot, Theresa A.; Rousseau, Francois; Tong, Liang; Wernimont, Amy K.; Young, Jasmine; Schwede, Torsten

    2011-01-01

    One goal of the CASP Community Wide Experiment on the Critical Assessment of Techniques for Protein Structure Prediction is to identify the current state of the art in protein structure prediction and modeling. A fundamental principle of CASP is blind prediction on a set of relevant protein targets, i.e. the participating computational methods are tested on a common set of experimental target proteins, for which the experimental structures are not known at the time of modeling. Therefore, the CASP experiment would not have been possible without broad support of the experimental protein structural biology community. In this manuscript, several experimental groups discuss the structures of the proteins which they provided as prediction targets for CASP9, highlighting structural and functional peculiarities of these structures: the long tail fibre protein gp37 from bacteriophage T4, the cyclic GMP-dependent protein kinase Iβ (PKGIβ) dimerization/docking domain, the ectodomain of the JTB (Jumping Translocation Breakpoint) transmembrane receptor, Autotaxin (ATX) in complex with an inhibitor, the DNA-Binding J-Binding Protein 1 (JBP1) domain essential for biosynthesis and maintenance of DNA base-J (β-D-glucosyl-hydroxymethyluracil) in Trypanosoma and Leishmania, an so far uncharacterized 73 residue domain from Ruminococcus gnavus with a fold typical for PDZ-like domains, a domain from the Phycobilisome (PBS) core-membrane linker (LCM) phycobiliprotein ApcE from Synechocystis, the Heat shock protein 90 (Hsp90) activators PFC0360w and PFC0270w from Plasmodium falciparum, and 2-oxo-3-deoxygalactonate kinase from Klebsiella pneumoniae. PMID:22020785

  2. Assessing Methods for Generalizing Experimental Impact Estimates to Target Populations

    ERIC Educational Resources Information Center

    Kern, Holger L.; Stuart, Elizabeth A.; Hill, Jennifer; Green, Donald P.

    2016-01-01

    Randomized experiments are considered the gold standard for causal inference because they can provide unbiased estimates of treatment effects for the experimental participants. However, researchers and policymakers are often interested in using a specific experiment to inform decisions about other target populations. In education research,…

  3. System-level multi-target drug discovery from natural products with applications to cardiovascular diseases.

    PubMed

    Zheng, Chunli; Wang, Jinan; Liu, Jianling; Pei, Mengjie; Huang, Chao; Wang, Yonghua

    2014-08-01

    The term systems pharmacology describes a field of study that uses computational and experimental approaches to broaden the view of drug actions rooted in molecular interactions and advance the process of drug discovery. The aim of this work is to stick out the role that the systems pharmacology plays across the multi-target drug discovery from natural products for cardiovascular diseases (CVDs). Firstly, based on network pharmacology methods, we reconstructed the drug-target and target-target networks to determine the putative protein target set of multi-target drugs for CVDs treatment. Secondly, we reintegrated a compound dataset of natural products and then obtained a multi-target compounds subset by virtual-screening process. Thirdly, a drug-likeness evaluation was applied to find the ADME-favorable compounds in this subset. Finally, we conducted in vitro experiments to evaluate the reliability of the selected chemicals and targets. We found that four of the five randomly selected natural molecules can effectively act on the target set for CVDs, indicating the reasonability of our systems-based method. This strategy may serve as a new model for multi-target drug discovery of complex diseases.

  4. Modeling the target acquisition performance of active imaging systems

    NASA Astrophysics Data System (ADS)

    Espinola, Richard L.; Jacobs, Eddie L.; Halford, Carl E.; Vollmerhausen, Richard; Tofsted, David H.

    2007-04-01

    Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

  5. Modeling the target acquisition performance of active imaging systems.

    PubMed

    Espinola, Richard L; Jacobs, Eddie L; Halford, Carl E; Vollmerhausen, Richard; Tofsted, David H

    2007-04-02

    Recent development of active imaging system technology in the defense and security community have driven the need for a theoretical understanding of its operation and performance in military applications such as target acquisition. In this paper, the modeling of active imaging systems, developed at the U.S. Army RDECOM CERDEC Night Vision & Electronic Sensors Directorate, is presented with particular emphasis on the impact of coherent effects such as speckle and atmospheric scintillation. Experimental results from human perception tests are in good agreement with the model results, validating the modeling of coherent effects as additional noise sources. Example trade studies on the design of a conceptual active imaging system to mitigate deleterious coherent effects are shown.

  6. Automatic target alignment of the Helios laser system

    NASA Astrophysics Data System (ADS)

    Liberman, I.; Viswanathan, V. K.; Klein, M.; Seery, B. D.

    1980-05-01

    An automatic target-alignment technique for the Helios laser facility is reported and verified experimentally. The desired alignment condition is completely described by an autocollimation test. A computer program examines the autocollimated return pattern from the surrogate target and correctly describes any changes required in mirror orientation to yield optimum target alignment with either aberrated or misaligned beams. Automated on-line target alignment is thus shown to be feasible.

  7. Neuroinflammatory targets and treatments for epilepsy validated in experimental models.

    PubMed

    Aronica, Eleonora; Bauer, Sebastian; Bozzi, Yuri; Caleo, Matteo; Dingledine, Raymond; Gorter, Jan A; Henshall, David C; Kaufer, Daniela; Koh, Sookyong; Löscher, Wolfgang; Louboutin, Jean-Pierre; Mishto, Michele; Norwood, Braxton A; Palma, Eleonora; Poulter, Michael O; Terrone, Gaetano; Vezzani, Annamaria; Kaminski, Rafal M

    2017-07-01

    A large body of evidence that has accumulated over the past decade strongly supports the role of inflammation in the pathophysiology of human epilepsy. Specific inflammatory molecules and pathways have been identified that influence various pathologic outcomes in different experimental models of epilepsy. Most importantly, the same inflammatory pathways have also been found in surgically resected brain tissue from patients with treatment-resistant epilepsy. New antiseizure therapies may be derived from these novel potential targets. An essential and crucial question is whether targeting these molecules and pathways may result in anti-ictogenesis, antiepileptogenesis, and/or disease-modification effects. Therefore, preclinical testing in models mimicking relevant aspects of epileptogenesis is needed to guide integrated experimental and clinical trial designs. We discuss the most recent preclinical proof-of-concept studies validating a number of therapeutic approaches against inflammatory mechanisms in animal models that could represent novel avenues for drug development in epilepsy. Finally, we suggest future directions to accelerate preclinical to clinical translation of these recent discoveries. Wiley Periodicals, Inc. © 2017 International League Against Epilepsy.

  8. Staircase-scene-based nonuniformity correction in aerial point target detection systems.

    PubMed

    Huo, Lijun; Zhou, Dabiao; Wang, Dejiang; Liu, Rang; He, Bin

    2016-09-01

    Focal-plane arrays (FPAs) are often interfered by heavy fixed-pattern noise, which severely degrades the detection rate and increases the false alarms in airborne point target detection systems. Thus, high-precision nonuniformity correction is an essential preprocessing step. In this paper, a new nonuniformity correction method is proposed based on a staircase scene. This correction method can compensate for the nonlinear response of the detector and calibrate the entire optical system with computational efficiency and implementation simplicity. Then, a proof-of-concept point target detection system is established with a long-wave Sofradir FPA. Finally, the local standard deviation of the corrected image and the signal-to-clutter ratio of the Airy disk of a Boeing B738 are measured to evaluate the performance of the proposed nonuniformity correction method. Our experimental results demonstrate that the proposed correction method achieves high-quality corrections.

  9. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation

    NASA Astrophysics Data System (ADS)

    Magro, G.; Molinelli, S.; Mairani, A.; Mirandola, A.; Panizza, D.; Russo, S.; Ferrari, A.; Valvo, F.; Fossati, P.; Ciocca, M.

    2015-09-01

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo® TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus® chamber. An EBT3® film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

  10. Dosimetric accuracy of a treatment planning system for actively scanned proton beams and small target volumes: Monte Carlo and experimental validation.

    PubMed

    Magro, G; Molinelli, S; Mairani, A; Mirandola, A; Panizza, D; Russo, S; Ferrari, A; Valvo, F; Fossati, P; Ciocca, M

    2015-09-07

    This study was performed to evaluate the accuracy of a commercial treatment planning system (TPS), in optimising proton pencil beam dose distributions for small targets of different sizes (5-30 mm side) located at increasing depths in water. The TPS analytical algorithm was benchmarked against experimental data and the FLUKA Monte Carlo (MC) code, previously validated for the selected beam-line. We tested the Siemens syngo(®) TPS plan optimisation module for water cubes fixing the configurable parameters at clinical standards, with homogeneous target coverage to a 2 Gy (RBE) dose prescription as unique goal. Plans were delivered and the dose at each volume centre was measured in water with a calibrated PTW Advanced Markus(®) chamber. An EBT3(®) film was also positioned at the phantom entrance window for the acquisition of 2D dose maps. Discrepancies between TPS calculated and MC simulated values were mainly due to the different lateral spread modeling and resulted in being related to the field-to-spot size ratio. The accuracy of the TPS was proved to be clinically acceptable in all cases but very small and shallow volumes. In this contest, the use of MC to validate TPS results proved to be a reliable procedure for pre-treatment plan verification.

  11. Experimental investigation of adiabatic compression and heating using collision of an MHD-driven jet with a gas target cloud for magnetized target fusion

    NASA Astrophysics Data System (ADS)

    Seo, Byonghoon; Li, Hui; Bellan, Paul

    2017-10-01

    We are studying magnetized target fusion using an experimental method where an imploding liner compressing a plasma is simulated by a high-speed MHD-driven plasma jet colliding with a gas target cloud. This has the advantage of being non-destructive so orders of magnitude more shots are possible. Since the actual density and temperature are much more modest than fusion-relevant values, the goal is to determine the scaling of the increase in density and temperature when an actual experimental plasma is adiabatically compressed. Two new-developed diagnostics are operating and providing data. The first new diagnostic is a fiber-coupled interferometer which measures line-integrated electron density not only as a function of time, but also as a function of position along the jet. The second new diagnostic is laser Thomson scattering which measures electron density and temperature at the location where the jet collides with the cloud. These diagnostics show that when the jet collides with a target cloud the jet slows down substantially and both the electron density and temperature increase. The experimental measurements are being compared with 3D MHD and hybrid kinetic numerical simulations that model the actual experimental geometry.

  12. A versatile targeting system with lentiviral vectors bearing the biotin-adaptor peptide

    PubMed Central

    Morizono, Kouki; Xie, Yiming; Helguera, Gustavo; Daniels, Tracy R.; Lane, Timothy F.; Penichet, Manuel L.; Chen, Irvin S. Y.

    2010-01-01

    Background Targeted gene transduction in vivo is the ultimate preferred method for gene delivery. We previously developed targeting lentiviral vectors that specifically recognize cell surface molecules with conjugated antibodies and mediate targeted gene transduction both in vitro and in vivo. Although effective in some experimental settings, the conjugation of virus with antibodies is mediated by the interaction between protein A and the Fc region of antibodies, which is not as stable as covalent conjugation. We have now developed a more stable conjugation strategy utilizing the interaction between avidin and biotin. Methods We inserted the biotin-adaptor-peptide, which was biotinylated by secretory biotin ligase at specific sites, into our targeting envelope proteins, enabling conjugation of the pseudotyped virus with avidin, streptavidin or neutravidin. Results When conjugated with avidin-antibody fusion proteins or the complex of avidin and biotinylated targeting molecules, the vectors could mediate specific transduction to targeted cells recognized by the targeting molecules. When conjugated with streptavidin-coated magnetic beads, transduction by the vectors was targeted to the locations of magnets. Conclusions This targeting vector system can be used for broad applications of targeted gene transduction using biotinylated targeting molecules or targeting molecules fused with avidin. PMID:19455593

  13. Radiological Protection and Nuclear Engineering Studies in Multi-MW Target Systems

    NASA Astrophysics Data System (ADS)

    Luis, Raul Fernandes

    goal of this work was to perform an optimisation study for the ISOLDE neutron converter and Vssion target system. The target system was simulated using FLUKA and the cross section codes TALYS and ABRABLA, with the objective of maximising the performance of the system for the production of pure beams of neutron-rich isotopes, suppressing the contaminations by undesired neutron-deficient isobars. Two alternative target systems were proposed in the optimisation studies; the simplest of the two, with some modiVcations, was built as a prototype and tested at ISOLDE. The experimental results clearly show that it is possible, with simple changes in the layouts of the target systems, to produce purer beams of neutron-rich isotopes around the doubly magic nuclei 78Ni and 132Sn. A study of Radiological Protection was also performed, comparing the performances of the prototype target system and the standard ISOLDE target system. None

  14. Targeting neutrophils in ischemic stroke: translational insights from experimental studies

    PubMed Central

    Jickling, Glen C; Liu, DaZhi; Ander, Bradley P; Stamova, Boryana; Zhan, Xinhua; Sharp, Frank R

    2015-01-01

    Neutrophils have key roles in ischemic brain injury, thrombosis, and atherosclerosis. As such, neutrophils are of great interest as targets to treat and prevent ischemic stroke. After stroke, neutrophils respond rapidly promoting blood–brain barrier disruption, cerebral edema, and brain injury. A surge of neutrophil-derived reactive oxygen species, proteases, and cytokines are released as neutrophils interact with cerebral endothelium. Neutrophils also are linked to the major processes that cause ischemic stroke, thrombosis, and atherosclerosis. Thrombosis is promoted through interactions with platelets, clotting factors, and release of prothrombotic molecules. In atherosclerosis, neutrophils promote plaque formation and rupture by generating oxidized-low density lipoprotein, enhancing monocyte infiltration, and degrading the fibrous cap. In experimental studies targeting neutrophils can improve stroke. However, early human studies have been met with challenges, and suggest that selective targeting of neutrophils may be required. Several properties of neutrophil are beneficial and thus may important to preserve in patients with stroke including antimicrobial, antiinflammatory, and neuroprotective functions. PMID:25806703

  15. miRTarBase update 2018: a resource for experimentally validated microRNA-target interactions.

    PubMed

    Chou, Chih-Hung; Shrestha, Sirjana; Yang, Chi-Dung; Chang, Nai-Wen; Lin, Yu-Ling; Liao, Kuang-Wen; Huang, Wei-Chi; Sun, Ting-Hsuan; Tu, Siang-Jyun; Lee, Wei-Hsiang; Chiew, Men-Yee; Tai, Chun-San; Wei, Ting-Yen; Tsai, Tzi-Ren; Huang, Hsin-Tzu; Wang, Chung-Yu; Wu, Hsin-Yi; Ho, Shu-Yi; Chen, Pin-Rong; Chuang, Cheng-Hsun; Hsieh, Pei-Jung; Wu, Yi-Shin; Chen, Wen-Liang; Li, Meng-Ju; Wu, Yu-Chun; Huang, Xin-Yi; Ng, Fung Ling; Buddhakosai, Waradee; Huang, Pei-Chun; Lan, Kuan-Chun; Huang, Chia-Yen; Weng, Shun-Long; Cheng, Yeong-Nan; Liang, Chao; Hsu, Wen-Lian; Huang, Hsien-Da

    2018-01-04

    MicroRNAs (miRNAs) are small non-coding RNAs of ∼ 22 nucleotides that are involved in negative regulation of mRNA at the post-transcriptional level. Previously, we developed miRTarBase which provides information about experimentally validated miRNA-target interactions (MTIs). Here, we describe an updated database containing 422 517 curated MTIs from 4076 miRNAs and 23 054 target genes collected from over 8500 articles. The number of MTIs curated by strong evidence has increased ∼1.4-fold since the last update in 2016. In this updated version, target sites validated by reporter assay that are available in the literature can be downloaded. The target site sequence can extract new features for analysis via a machine learning approach which can help to evaluate the performance of miRNA-target prediction tools. Furthermore, different ways of browsing enhance user browsing specific MTIs. With these improvements, miRTarBase serves as more comprehensively annotated, experimentally validated miRNA-target interactions databases in the field of miRNA related research. miRTarBase is available at http://miRTarBase.mbc.nctu.edu.tw/. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. DrugECs: An Ensemble System with Feature Subspaces for Accurate Drug-Target Interaction Prediction

    PubMed Central

    Jiang, Jinjian; Wang, Nian; Zhang, Jun

    2017-01-01

    Background Drug-target interaction is key in drug discovery, especially in the design of new lead compound. However, the work to find a new lead compound for a specific target is complicated and hard, and it always leads to many mistakes. Therefore computational techniques are commonly adopted in drug design, which can save time and costs to a significant extent. Results To address the issue, a new prediction system is proposed in this work to identify drug-target interaction. First, drug-target pairs are encoded with a fragment technique and the software “PaDEL-Descriptor.” The fragment technique is for encoding target proteins, which divides each protein sequence into several fragments in order and encodes each fragment with several physiochemical properties of amino acids. The software “PaDEL-Descriptor” creates encoding vectors for drug molecules. Second, the dataset of drug-target pairs is resampled and several overlapped subsets are obtained, which are then input into kNN (k-Nearest Neighbor) classifier to build an ensemble system. Conclusion Experimental results on the drug-target dataset showed that our method performs better and runs faster than the state-of-the-art predictors. PMID:28744468

  18. Detection technique of targets for missile defense system

    NASA Astrophysics Data System (ADS)

    Guo, Hua-ling; Deng, Jia-hao; Cai, Ke-rong

    2009-11-01

    Ballistic missile defense system (BMDS) is a weapon system for intercepting enemy ballistic missiles. It includes ballistic-missile warning system, target discrimination system, anti-ballistic-missile guidance systems, and command-control communication system. Infrared imaging detection and laser imaging detection are widely used in BMDS for surveillance, target detection, target tracking, and target discrimination. Based on a comprehensive review of the application of target-detection techniques in the missile defense system, including infrared focal plane arrays (IRFPA), ground-based radar detection technology, 3-dimensional imaging laser radar with a photon counting avalanche photodiode (APD) arrays and microchip laser, this paper focuses on the infrared and laser imaging detection techniques in missile defense system, as well as the trends for their future development.

  19. Tracking a Non-Cooperative Target Using Real-Time Stereovision-Based Control: An Experimental Study.

    PubMed

    Shtark, Tomer; Gurfil, Pini

    2017-03-31

    Tracking a non-cooperative target is a challenge, because in unfamiliar environments most targets are unknown and unspecified. Stereovision is suited to deal with this issue, because it allows to passively scan large areas and estimate the relative position, velocity and shape of objects. This research is an experimental effort aimed at developing, implementing and evaluating a real-time non-cooperative target tracking methods using stereovision measurements only. A computer-vision feature detection and matching algorithm was developed in order to identify and locate the target in the captured images. Three different filters were designed for estimating the relative position and velocity, and their performance was compared. A line-of-sight control algorithm was used for the purpose of keeping the target within the field-of-view. Extensive analytical and numerical investigations were conducted on the multi-view stereo projection equations and their solutions, which were used to initialize the different filters. This research shows, using an experimental and numerical evaluation, the benefits of using the unscented Kalman filter and the total least squares technique in the stereovision-based tracking problem. These findings offer a general and more accurate method for solving the static and dynamic stereovision triangulation problems and the concomitant line-of-sight control.

  20. Tracking a Non-Cooperative Target Using Real-Time Stereovision-Based Control: An Experimental Study

    PubMed Central

    Shtark, Tomer; Gurfil, Pini

    2017-01-01

    Tracking a non-cooperative target is a challenge, because in unfamiliar environments most targets are unknown and unspecified. Stereovision is suited to deal with this issue, because it allows to passively scan large areas and estimate the relative position, velocity and shape of objects. This research is an experimental effort aimed at developing, implementing and evaluating a real-time non-cooperative target tracking methods using stereovision measurements only. A computer-vision feature detection and matching algorithm was developed in order to identify and locate the target in the captured images. Three different filters were designed for estimating the relative position and velocity, and their performance was compared. A line-of-sight control algorithm was used for the purpose of keeping the target within the field-of-view. Extensive analytical and numerical investigations were conducted on the multi-view stereo projection equations and their solutions, which were used to initialize the different filters. This research shows, using an experimental and numerical evaluation, the benefits of using the unscented Kalman filter and the total least squares technique in the stereovision-based tracking problem. These findings offer a general and more accurate method for solving the static and dynamic stereovision triangulation problems and the concomitant line-of-sight control. PMID:28362338

  1. Hybrid-drive implosion system for ICF targets

    DOEpatents

    Mark, J.W.K.

    1987-10-14

    Hybrid-drive implosion systems for ICF targets are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator surroundingly disposed around fusion fuel. The ablator is first compressed to higher density by a laser system, or by an ion beam system, that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system that is optimized for this second phase of operation of the target. The fusion fuel is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion. 3 figs.

  2. Experimental study on ablative stabilization of Rayleigh-Taylor instability of laser-irradiated targets

    NASA Astrophysics Data System (ADS)

    Shigemori, Keisuke; Sakaiya, Tatsuhiko; Otani, Kazuto; Fujioka, Shinsuke; Nakai, Mitsuo; Azechi, Hiroshi; Shiraga, Hiroyuki; Tamari, Yohei; Okuno, Kazuki; Sunahara, Atsushi; Nagatomo, Hideo; Murakami, Masakatsu; Nishihara, Katsunobu; Izawa, Yasukazu

    2004-09-01

    Hydrodynamic instabilities are key issues of the physics of inertial confinement fusion (ICF) targets. Among the instabilities, Rayleigh-Taylor (RT) instability is the most important because it gives the largest growth factor in the ICF targets. Perturbations on the laser irradiated surface grow exponentially, but the growth rate is reduced by ablation flow. The growth rate γ is written as Takabe-Betti formula: γ = [kg/(1+kL)]1/2-βkm/pa, where k is wave number of the perturbation, g is acceleration, L is density scale-length, β is a coefficient, m is mass ablation rate per unit surface, and ρa is density at the ablation front. We experimentally measured all the parameters in the formula for polystyrene (CH) targets. Experiments were done on the HIPER laser facility at Institute of Laser Engineering, Osaka University. We found that the β value in the formula is ~ 1.7, which is in good agreements with the theoretical prediction, whereas the β for certain perturbation wavelengths are larger than the prediction. This disagreement between the experiment and the theory is mainly due to the deformation of the cutoff surface, which is created by non-uniform ablation flow from the ablation surface. We also found that high-Z doped plastic targets have multiablation structure, which can reduce the RT growth rate. When a low-Z target with high-Z dopant is irradiated by laser, radiation due to the high-Z dopant creates secondary ablation front deep inside the target. Since, the secondary ablation front is ablated by x-rays, the mass ablation rate is larger than the laser-irradiated ablation surface, that is, further reduction of the RT growth is expected. We measured the RT growth rate of Br-doped polystyrene targets. The experimental results indicate that of the CHBr targets show significantly small growth rate, which is very good news for the design of the ICF targets.

  3. Guidance system for laser targets

    DOEpatents

    Porter, Gary D.; Bogdanoff, Anatoly

    1978-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  4. Image-based in vivo assessment of targeting accuracy of stereotactic brain surgery in experimental rodent models

    NASA Astrophysics Data System (ADS)

    Rangarajan, Janaki Raman; Vande Velde, Greetje; van Gent, Friso; de Vloo, Philippe; Dresselaers, Tom; Depypere, Maarten; van Kuyck, Kris; Nuttin, Bart; Himmelreich, Uwe; Maes, Frederik

    2016-11-01

    Stereotactic neurosurgery is used in pre-clinical research of neurological and psychiatric disorders in experimental rat and mouse models to engraft a needle or electrode at a pre-defined location in the brain. However, inaccurate targeting may confound the results of such experiments. In contrast to the clinical practice, inaccurate targeting in rodents remains usually unnoticed until assessed by ex vivo end-point histology. We here propose a workflow for in vivo assessment of stereotactic targeting accuracy in small animal studies based on multi-modal post-operative imaging. The surgical trajectory in each individual animal is reconstructed in 3D from the physical implant imaged in post-operative CT and/or its trace as visible in post-operative MRI. By co-registering post-operative images of individual animals to a common stereotaxic template, targeting accuracy is quantified. Two commonly used neuromodulation regions were used as targets. Target localization errors showed not only variability, but also inaccuracy in targeting. Only about 30% of electrodes were within the subnucleus structure that was targeted and a-specific adverse effects were also noted. Shifting from invasive/subjective 2D histology towards objective in vivo 3D imaging-based assessment of targeting accuracy may benefit a more effective use of the experimental data by excluding off-target cases early in the study.

  5. Experimental research on the relation between food price changes and food-purchasing patterns: a targeted review.

    PubMed

    Epstein, Leonard H; Jankowiak, Noelle; Nederkoorn, Chantal; Raynor, Hollie A; French, Simone A; Finkelstein, Eric

    2012-04-01

    One way in which to modify food purchases is to change prices through tax policy, subsidy policy, or both. We reviewed the growing body of experimental research conducted in the laboratory and in the field that investigates the following: the extent to which price changes influence purchases of targeted and nontargeted foods, total energy, or macronutrients purchased; the interaction of price changes with adjunctive interventions; and moderators of sensitivity to price changes. After a brief overview of economic principles and observational research that addresses these issues, we present a targeted review of experimental research. Experimental research suggests that price changes modify purchases of targeted foods, but research on the overall nutritional quality of purchases is mixed because of substitution effects. There is mixed support for combining price changes with adjunctive interventions, and there are no replicated findings on moderators to price sensitivity in experiments. Additional focused research is needed to better inform food policy development with the aim of improving eating behavior and preventing obesity.

  6. Allegany Ballistics Lab: sensor test target system

    NASA Astrophysics Data System (ADS)

    Eaton, Deran S.

    2011-06-01

    Leveraging the Naval Surface Warfare Center, Indian Head Division's historical experience in weapon simulation, Naval Sea Systems Command commissioned development of a remote-controlled, digitally programmable Sensor Test Target as part of a modern, outdoor hardware-in-the-loop test system for ordnance-related guidance, navigation and control systems. The overall Target system design invokes a sciences-based, "design of automated experiments" approach meant to close the logistical distance between sensor engineering and developmental T&E in outdoor conditions over useful real world distances. This enables operating modes that employ broad spectrum electromagnetic energy in many a desired combination, variably generated using a Jet Engine Simulator, a multispectral infrared emitter array, optically enhanced incandescent Flare Simulators, Emitter/Detector mounts, and an RF corner reflector kit. As assembled, the recently tested Sensor Test Target prototype being presented can capably provide a full array of useful RF and infrared target source simulations for RDT&E use with developmental and existing sensors. Certain Target technologies are patent pending, with potential spinoffs in aviation, metallurgy and biofuels processing, while others are variations on well-established technology. The Sensor Test Target System is planned for extended installation at Allegany Ballistics Laboratory (Rocket Center, WV).

  7. Hybrid-drive implosion system for ICF targets

    DOEpatents

    Mark, James W.

    1988-08-02

    Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

  8. Hybrid-drive implosion system for ICF targets

    DOEpatents

    Mark, James W.

    1988-01-01

    Hybrid-drive implosion systems (20,40) for ICF targets (10,22,42) are described which permit a significant increase in target gain at fixed total driver energy. The ICF target is compressed in two phases, an initial compression phase and a final peak power phase, with each phase driven by a separate, optimized driver. The targets comprise a hollow spherical ablator (12) surroundingly disposed around fusion fuel (14). The ablator is first compressed to higher density by a laser system (24), or by an ion beam system (44), that in each case is optimized for this initial phase of compression of the target. Then, following compression of the ablator, energy is directly delivered into the compressed ablator by an ion beam driver system (30,48) that is optimized for this second phase of operation of the target. The fusion fuel (14) is driven, at high gain, to conditions wherein fusion reactions occur. This phase separation allows hydrodynamic efficiency and energy deposition uniformity to be individually optimized, thereby securing significant advantages in energy gain. In additional embodiments, the same or separate drivers supply energy for ICF target implosion.

  9. Experimental demonstration of laser to x-ray conversion enhancements with low density gold targets

    DOE PAGES

    Shang, Wanli; Yang, Jiamin; Zhang, Wenhai; ...

    2016-02-12

    The enhancement of laser to x-ray conversion efficiencies using low density gold targets [W. L. Shang, J. M. Yang, and Y. S. Dong, Appl. Phys. Lett. 102, 094105 (2013)] is demonstrated. Laser to x-ray conversion efficiencies with 6.3% and 12% increases are achieved with target densities of 1 and 0.25 g/cm 3, when compared with that of a solid gold target (19.3 g/cm 3). Experimental data and numerical simulations are in good agreement. Lastly, the enhancement is caused by larger x-ray emission zone lengths formed in low density targets, which is in agreement with the simulation results.

  10. Experimental demonstration of laser to x-ray conversion enhancements with low density gold targets

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

    Shang, Wanli; Yang, Jiamin; Zhang, Wenhai

    The enhancement of laser to x-ray conversion efficiencies using low density gold targets [W. L. Shang, J. M. Yang, and Y. S. Dong, Appl. Phys. Lett. 102, 094105 (2013)] is demonstrated. Laser to x-ray conversion efficiencies with 6.3% and 12% increases are achieved with target densities of 1 and 0.25 g/cm 3, when compared with that of a solid gold target (19.3 g/cm 3). Experimental data and numerical simulations are in good agreement. Lastly, the enhancement is caused by larger x-ray emission zone lengths formed in low density targets, which is in agreement with the simulation results.

  11. A real-time tracking system of infrared dim and small target based on FPGA and DSP

    NASA Astrophysics Data System (ADS)

    Rong, Sheng-hui; Zhou, Hui-xin; Qin, Han-lin; Wang, Bing-jian; Qian, Kun

    2014-11-01

    A core technology in the infrared warning system is the detection tracking of dim and small targets with complicated background. Consequently, running the detection algorithm on the hardware platform has highly practical value in the military field. In this paper, a real-time detection tracking system of infrared dim and small target which is used FPGA (Field Programmable Gate Array) and DSP (Digital Signal Processor) as the core was designed and the corresponding detection tracking algorithm and the signal flow is elaborated. At the first stage, the FPGA obtain the infrared image sequence from the sensor, then it suppresses background clutter by mathematical morphology method and enhances the target intensity by Laplacian of Gaussian operator. At the second stage, the DSP obtain both the original image and the filtered image form the FPGA via the video port. Then it segments the target from the filtered image by an adaptive threshold segmentation method and gets rid of false target by pipeline filter. Experimental results show that our system can achieve higher detection rate and lower false alarm rate.

  12. Experimental investigation of correlation between fading and glint for aircraft targets

    NASA Astrophysics Data System (ADS)

    Wallin, C. M.; Aas, B.

    The correlation between the fading and glint of aircraft targets is investigated experimentally using a conventional amplitude comparison three-channel monopulse radar operating in the Ku-band. A significant correlation is found between the RCS and the variance of the angle error signals; this correlation seems to be independent of the aspect angle. The correlation between the RCS and the angle error signals themselves, however, is found to be very small.

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

    PubMed

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

    2013-10-01

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

  14. Phytochemicals as multi-target inhibitors of the inflammatory pathway- A modeling and experimental study.

    PubMed

    Devi, Nisha S; Ramanan, Meera; Paragi-Vedanthi, Padmapriya; Doble, Mukesh

    2017-03-11

    The arachidonic acid pathway consists of several enzymes and targeting them is favored for developing anti-inflammatory drugs. However, till date the current drugs are generally active against a single target, leading to undesirable side-effects. Phytochemicals are known to inhibit multiple targets simultaneously and hence, an attempt is made here to investigate their suitability. A pharmacophore based study is performed with three sets of reported phytochemicals namely, dual 5-LOX/mPGES1, alkaloids and FLAP inhibitors. The analysis indicated that phenylpropanoids (including ferulic acid) and benzoic acids derivatives, and berberine mapped onto these pharmacophores with three hydrophobic centroids and an acceptor feature. 2,4,5-trimethoxy (7) and 3,4-dimethoxy cinnamic acids (8) mapped onto all the three pharmacophores. Experimental studies indicated that berberine inhibited 5-LOX (100 μM) and PGE 2 (50 μM) production by 72.2 and 72.0% and ferulic acid by 74.3 and 54.4% respectively. This approach offers a promising theoretical combined with experimental strategy for designing novel molecules against inflammatory enzymes. Copyright © 2017 Elsevier Inc. All rights reserved.

  15. Real-time target tracking and locating system for UAV

    NASA Astrophysics Data System (ADS)

    Zhang, Chao; Tang, Linbo; Fu, Huiquan; Li, Maowen

    2017-07-01

    In order to achieve real-time target tracking and locating for UAV, a reliable processing system is built on the embedded platform. Firstly, the video image is acquired in real time by the photovoltaic system on the UAV. When the target information is known, KCF tracking algorithm is adopted to track the target. Then, the servo is controlled to rotate with the target, when the target is in the center of the image, the laser ranging module is opened to obtain the distance between the UAV and the target. Finally, to combine with UAV flight parameters obtained by BeiDou navigation system, through the target location algorithm to calculate the geodetic coordinates of the target. The results show that the system is stable for real-time tracking of targets and positioning.

  16. Deformation and Fracture Behavior of Steel Projectiles Impact AD95 Ceramic Targets-Experimental Investigation

    NASA Astrophysics Data System (ADS)

    Wei, Gang; Zhang, Wei

    2013-06-01

    The deformation and fracture behavior of steel projectile impacting ceramic target is an interesting investigation topic. The deformation and failure behavior of projectile and target was investigated experimentally in the normal impact by different velocities. Lab-scale ballistic tests of AD95 ceramic targets with 20 mm thickness against two different hardness 38CrSi steel projectiles with 7.62 mm diameter have been conducted at a range of velocities from 100 to 1000 m/s. Experimental results show that, with the impact velocity increasing, for the soft projectiles, the deformation and fracture modes were mushrooming, shear cracking, petalling and fragmentation(with large fragments and less number), respectively; for the hard projectiles there are three deformation and fracture modes: mushrooming, shearing cracking and fragmentation(with small fragments and large number). All projectiles were rebound after impact. But, with the velocity change, the target failure modes have changed. At low velocity, only radial cracks were found; then circumferential cracks appeared with the increasing velocity; the ceramic cone occurred when the velocity reached 400 m/s above, and manifested in two forms: front surface intact at lower velocity and perforated at higher velocity. The higher velocity, the fragment size is smaller and more uniform distribution. The difference of ceramic target damage is not obvious after impacted by two kinds of projectiles with different hardness at the same velocity. National Natural Science Foundation of China (No.: 11072072).

  17. VIRmiRNA: a comprehensive resource for experimentally validated viral miRNAs and their targets.

    PubMed

    Qureshi, Abid; Thakur, Nishant; Monga, Isha; Thakur, Anamika; Kumar, Manoj

    2014-01-01

    Viral microRNAs (miRNAs) regulate gene expression of viral and/or host genes to benefit the virus. Hence, miRNAs play a key role in host-virus interactions and pathogenesis of viral diseases. Lately, miRNAs have also shown potential as important targets for the development of novel antiviral therapeutics. Although several miRNA and their target repositories are available for human and other organisms in literature, but a dedicated resource on viral miRNAs and their targets are lacking. Therefore, we have developed a comprehensive viral miRNA resource harboring information of 9133 entries in three subdatabases. This includes 1308 experimentally validated miRNA sequences with their isomiRs encoded by 44 viruses in viral miRNA ' VIRMIRNA: ' and 7283 of their target genes in ' VIRMIRTAR': . Additionally, there is information of 542 antiviral miRNAs encoded by the host against 24 viruses in antiviral miRNA ' AVIRMIR': . The web interface was developed using Linux-Apache-MySQL-PHP (LAMP) software bundle. User-friendly browse, search, advanced search and useful analysis tools are also provided on the web interface. VIRmiRNA is the first specialized resource of experimentally proven virus-encoded miRNAs and their associated targets. This database would enhance the understanding of viral/host gene regulation and may also prove beneficial in the development of antiviral therapeutics. Database URL: http://crdd.osdd.net/servers/virmirna. © The Author(s) 2014. Published by Oxford University Press.

  18. Experimental research on the relation between food price changes and food-purchasing patterns: a targeted review1234

    PubMed Central

    Epstein, Leonard H; Jankowiak, Noelle; Nederkoorn, Chantal; Raynor, Hollie A; French, Simone A; Finkelstein, Eric

    2012-01-01

    One way in which to modify food purchases is to change prices through tax policy, subsidy policy, or both. We reviewed the growing body of experimental research conducted in the laboratory and in the field that investigates the following: the extent to which price changes influence purchases of targeted and nontargeted foods, total energy, or macronutrients purchased; the interaction of price changes with adjunctive interventions; and moderators of sensitivity to price changes. After a brief overview of economic principles and observational research that addresses these issues, we present a targeted review of experimental research. Experimental research suggests that price changes modify purchases of targeted foods, but research on the overall nutritional quality of purchases is mixed because of substitution effects. There is mixed support for combining price changes with adjunctive interventions, and there are no replicated findings on moderators to price sensitivity in experiments. Additional focused research is needed to better inform food policy development with the aim of improving eating behavior and preventing obesity. PMID:22378726

  19. Temperature Controller System for Gas Gun Targets

    NASA Astrophysics Data System (ADS)

    Bucholtz, Scott; Sheffield, Stephen

    2005-07-01

    A temperature controller system capable of heating and cooling gas gun targets over the range -75 C to +200 C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge with integrated thermocouples was developed to measure the internal temperature of the target. Using this system shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful tests were completed on Teflon samples. This work was supported by the NNSA Enhanced Surveillance Campaign through contract DE-ACO4-01AL66850.

  20. Temperature Controller System for Gas Gun Targets

    NASA Astrophysics Data System (ADS)

    Bucholtz, S. M.; Gehr, R. J.; Rupp, T. D.; Sheffield, S. A.; Robbins, D. L.

    2006-07-01

    A temperature controller system capable of heating and cooling gas gun targets over the range -75°C to +120°C was designed and tested. The system uses cold nitrogen gas from a liquid nitrogen Dewar for cooling and compressed air for heating. Two gas flow heaters control the gas temperature for both heating and cooling. One heater controls the temperature of the target mounting plate and the other the temperature of a copper tubing coil surrounding the target. Each heater is separately adjustable, so the target material will achieve a uniform temperature throughout its volume. A magnetic gauge membrane with integrated thermocouples was developed to measure the internal temperature of the target. Using this system, multiple magnetic gauge shock experiments, including equation-of-state measurements and shock initiation of high explosives, can be performed over a range of initial temperatures. Successful heating and cooling tests were completed on Teflon samples.

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

    PubMed

    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.

  2. Target isolation system, high power laser and laser peening method and system using same

    DOEpatents

    Dane, C. Brent; Hackel, Lloyd A.; Harris, Fritz

    2007-11-06

    A system for applying a laser beam to work pieces, includes a laser system producing a high power output beam. Target delivery optics are arranged to deliver the output beam to a target work piece. A relay telescope having a telescope focal point is placed in the beam path between the laser system and the target delivery optics. The relay telescope relays an image between an image location near the output of the laser system and an image location near the target delivery optics. A baffle is placed at the telescope focal point between the target delivery optics and the laser system to block reflections from the target in the target delivery optics from returning to the laser system and causing damage.

  3. Cytotoxic chromosomal targeting by CRISPR/Cas systems can reshape bacterial genomes and expel or remodel pathogenicity islands.

    PubMed

    Vercoe, Reuben B; Chang, James T; Dy, Ron L; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R; Fineran, Peter C

    2013-04-01

    In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas-mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA-targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity.

  4. An Experimental Study on the Attribution of Personality Traits to Bullies and Targets in a Workplace Setting

    PubMed Central

    Pallesen, Ståle; Nielsen, Morten B.; Magerøy, Nils; Andreassen, Cecilie S.; Einarsen, Ståle

    2017-01-01

    Previous studies on the personality of bullies and targets have exclusively been based on self-report. Against this backdrop we conducted a between group experimental vignette study with three conditions, describing a bully, a target and a control, respectively. Students (n = 242) were recruited as participants and rated the target on the observer rating version of the NEO Five Factor Inventory-Revised reflecting the personality dimensions Neuroticism, Extroversion, Openness to experience, Agreeableness and Conscientiousness. A MANOVA showed an overall significant effect of the experimental conditions. On Neuroticism significant differences between all conditions were found with targets rated highest and the control lowest. In terms of Extroversion the target was rated as lower than the control and the bully. No main effect was found for Openness. On Agreeableness the bully was rated as lower than both the target and the control. The bully was rated lower on Conscientiousness than the control. The significant differences reflected medium to large effect sizes. By and large the results are in agreement with comparable self-report data. The results are discussed in terms of practical implications and directions for future research are outlined. PMID:28690574

  5. An Experimental Study on the Attribution of Personality Traits to Bullies and Targets in a Workplace Setting.

    PubMed

    Pallesen, Ståle; Nielsen, Morten B; Magerøy, Nils; Andreassen, Cecilie S; Einarsen, Ståle

    2017-01-01

    Previous studies on the personality of bullies and targets have exclusively been based on self-report. Against this backdrop we conducted a between group experimental vignette study with three conditions, describing a bully, a target and a control, respectively. Students ( n = 242) were recruited as participants and rated the target on the observer rating version of the NEO Five Factor Inventory-Revised reflecting the personality dimensions Neuroticism, Extroversion, Openness to experience, Agreeableness and Conscientiousness. A MANOVA showed an overall significant effect of the experimental conditions. On Neuroticism significant differences between all conditions were found with targets rated highest and the control lowest. In terms of Extroversion the target was rated as lower than the control and the bully. No main effect was found for Openness. On Agreeableness the bully was rated as lower than both the target and the control. The bully was rated lower on Conscientiousness than the control. The significant differences reflected medium to large effect sizes. By and large the results are in agreement with comparable self-report data. The results are discussed in terms of practical implications and directions for future research are outlined.

  6. Extended Fitts' model of pointing time in eye-gaze input system - Incorporating effects of target shape and movement direction into modeling.

    PubMed

    Murata, Atsuo; Fukunaga, Daichi

    2018-04-01

    This study attempted to investigate the effects of the target shape and the movement direction on the pointing time using an eye-gaze input system and extend Fitts' model so that these factors are incorporated into the model and the predictive power of Fitts' model is enhanced. The target shape, the target size, the movement distance, and the direction of target presentation were set as within-subject experimental variables. The target shape included: a circle, and rectangles with an aspect ratio of 1:1, 1:2, 1:3, and 1:4. The movement direction included eight directions: upper, lower, left, right, upper left, upper right, lower left, and lower right. On the basis of the data for identifying the effects of the target shape and the movement direction on the pointing time, an attempt was made to develop a generalized and extended Fitts' model that took into account the movement direction and the target shape. As a result, the generalized and extended model was found to fit better to the experimental data, and be more effective for predicting the pointing time for a variety of human-computer interaction (HCI) task using an eye-gaze input system. Copyright © 2017. Published by Elsevier Ltd.

  7. Cryogenic target system for hydrogen layering

    DOE PAGES

    Parham, T.; Kozioziemski, B.; Atkinson, D.; ...

    2015-11-24

    Here, a cryogenic target positioning system was designed and installed on the National Ignition Facility (NIF) target chamber. This instrument incorporates the ability to fill, form, and characterize the NIF targets with hydrogen isotopes needed for ignition experiments inside the NIF target bay then transport and position them in the target chamber. This effort brought to fruition years of research in growing and metrologizing high-quality hydrogen fuel layers and landed it in an especially demanding operations environment in the NIF facility. D-T (deuterium-tritium) layers for NIF ignition experiments have extremely tight specifications and must be grown in a very highlymore » constrained environment: a NIF ignition target inside a cryogenic target positioner inside the NIF target bay. Exquisite control of temperature, pressure, contaminant level, and thermal uniformity are necessary throughout seed formation and layer growth to create an essentially-groove-free single crystal layer.« less

  8. Target for production of X-rays

    NASA Astrophysics Data System (ADS)

    Korenev, S. A.

    2004-09-01

    The patented new type of X-ray target is considered in this report. The main concept of the target consists in developing a sandwich structure depositing a coating of materials with high Z on the substrate with low Z, high thermal conductivity and high thermal stability. The target presents multiple layers system. The thermal conditions for X-ray target are discussed. The experimental results for Ta target on the Al and Cu substrates are presented.

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

    PubMed

    Pritchard, Leighton; Birch, Paul

    2011-04-01

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

  10. Cytotoxic Chromosomal Targeting by CRISPR/Cas Systems Can Reshape Bacterial Genomes and Expel or Remodel Pathogenicity Islands

    PubMed Central

    Vercoe, Reuben B.; Chang, James T.; Dy, Ron L.; Taylor, Corinda; Gristwood, Tamzin; Clulow, James S.; Richter, Corinna; Przybilski, Rita; Pitman, Andrew R.; Fineran, Peter C.

    2013-01-01

    In prokaryotes, clustered regularly interspaced short palindromic repeats (CRISPRs) and their associated (Cas) proteins constitute a defence system against bacteriophages and plasmids. CRISPR/Cas systems acquire short spacer sequences from foreign genetic elements and incorporate these into their CRISPR arrays, generating a memory of past invaders. Defence is provided by short non-coding RNAs that guide Cas proteins to cleave complementary nucleic acids. While most spacers are acquired from phages and plasmids, there are examples of spacers that match genes elsewhere in the host bacterial chromosome. In Pectobacterium atrosepticum the type I-F CRISPR/Cas system has acquired a self-complementary spacer that perfectly matches a protospacer target in a horizontally acquired island (HAI2) involved in plant pathogenicity. Given the paucity of experimental data about CRISPR/Cas–mediated chromosomal targeting, we examined this process by developing a tightly controlled system. Chromosomal targeting was highly toxic via targeting of DNA and resulted in growth inhibition and cellular filamentation. The toxic phenotype was avoided by mutations in the cas operon, the CRISPR repeats, the protospacer target, and protospacer-adjacent motif (PAM) beside the target. Indeed, the natural self-targeting spacer was non-toxic due to a single nucleotide mutation adjacent to the target in the PAM sequence. Furthermore, we show that chromosomal targeting can result in large-scale genomic alterations, including the remodelling or deletion of entire pre-existing pathogenicity islands. These features can be engineered for the targeted deletion of large regions of bacterial chromosomes. In conclusion, in DNA–targeting CRISPR/Cas systems, chromosomal interference is deleterious by causing DNA damage and providing a strong selective pressure for genome alterations, which may have consequences for bacterial evolution and pathogenicity. PMID:23637624

  11. Multi-Stage System for Automatic Target Recognition

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  12. The Gut Microbiome as Therapeutic Target in Central Nervous System Diseases: Implications for Stroke.

    PubMed

    Winek, Katarzyna; Dirnagl, Ulrich; Meisel, Andreas

    2016-10-01

    Research on commensal microbiota and its contribution to health and disease is a new and very dynamically developing field of biology and medicine. Recent experimental and clinical investigations underscore the importance of gut microbiota in the pathogenesis and course of stroke. Importantly, microbiota may influence the outcome of cerebral ischemia by modulating central nervous system antigen-specific immune responses. In this review we summarize studies linking gut microbiota with physiological function and disorders of the central nervous system. Based on these insights we speculate about targeting the gut microbiome in order to treat stroke.

  13. A combined experimental and numerical approach for the control and monitoring of the SPES target during operation at high temperature

    NASA Astrophysics Data System (ADS)

    Ballan, Michele; Manzolaro, Mattia; Meneghetti, Giovanni; Andrighetto, Alberto; Monetti, Alberto; Bisoffi, Giovanni; Prete, Gianfranco

    2016-06-01

    The SPES project at INFN-LNL aims at the production of neutron-rich Radioactive Ion Beams (RIBs) using the ISOL (Isotope Separation On Line) technique. A 40 MeV 200 μA proton beam will directly impinge a uranium carbide target, generating approximately 1013 fissions per second. The target system is installed under vacuum inside a water-cooled chamber, and have to maintain high working temperatures, close to 2000 °C. During operation the proton beam provides the heating power required to keep the target at the desired temperature level. As a consequence, its characteristics have to be strictly controlled in order to avoid undesired overheating. According to the original design of the control system, the proton beam can be suddenly interrupted in case of out of range vacuum or cooling water flow levels. With the aim to improve the reliability of the control system a set of temperature sensors has been installed close to the target. Their types and installation positions were defined taking into consideration the detailed information coming from a dedicated thermal-electric model that allowed to investigate the most critical and inaccessible target hot-spots. This work is focused on the definition and experimental validation of the aforementioned numerical model. Its results were used to appropriately install two type C thermocouples, a PT100 thermo-resistance and a residual primary beam current detector. In addition the numerical model will be used for the definition of appropriate thresholds for each installed temperature sensor, since it allows to define a relationship between the locally measured values with the overall calculated temperature field. In case of over temperatures the monitoring system will send warning signals or in case interrupt the proton beam.

  14. Repetitive output laser system and method using target reflectivity

    DOEpatents

    Johnson, Roy R.

    1978-01-01

    An improved laser system and method for implosion of a thermonuclear fuel pellet in which that portion of a laser pulse reflected by the target pellet is utilized in the laser system to initiate a succeeding target implosion, and in which the energy stored in the laser system to amplify the initial laser pulse, but not completely absorbed thereby, is used to amplify succeeding laser pulses initiated by target reflection.

  15. The Research Progress of Targeted Drug Delivery Systems

    NASA Astrophysics Data System (ADS)

    Zhan, Jiayin; Ting, Xizi Liang; Zhu, Junjie

    2017-06-01

    Targeted drug delivery system (DDS) means to selectively transport drugs to targeted tissues, organs, and cells through a variety of drugs carrier. It is usually designed to improve the pharmacological and therapeutic properties of conventional drugs and to overcome problems such as limited solubility, drug aggregation, poor bio distribution and lack of selectivity, controlling drug release carrier and to reduce normal tissue damage. With the characteristics of nontoxic and biodegradable, it can increase the retention of drug in lesion site and the permeability, improve the concentration of the drug in lesion site. at present, there are some kinds of DDS using at test phase, such as slow controlled release drug delivery system, targeted drug delivery systems, transdermal drug delivery system, adhesion dosing system and so on. This paper makes a review for DDS.

  16. Targeted Help for Spoken Dialogue Systems: Intelligent Feedback Improves Naive Users' Performance

    NASA Technical Reports Server (NTRS)

    Hockey, Beth Ann; Lemon, Oliver; Campana, Ellen; Hiatt, Laura; Aist, Gregory; Hieronymous, Jim; Gruenstein, Alexander; Dowding, John

    2003-01-01

    We present experimental evidence that providing naive users of a spoken dialogue system with immediate help messages related to their out-of-coverage utterances improves their success in using the system. A grammar-based recognizer and a Statistical Language Model (SLM) recognizer are run simultaneously. If the grammar-based recognizer suceeds, the less accurate SLM recognizer hypothesis is not used. When the grammar-based recognizer fails and the SLM recognizer produces a recognition hypothesis, this result is used by the Targeted Help agent to give the user feed-back on what was recognized, a diagnosis of what was problematic about the utterance, and a related in-coverage example. The in-coverage example is intended to encourage alignment between user inputs and the language model of the system. We report on controlled experiments on a spoken dialogue system for command and control of a simulated robotic helicopter.

  17. Targeting MOG expression to dendritic cells delays onset of experimental autoimmune disease.

    PubMed

    Ko, Hyun-Ja; Chung, Jie-Yu; Nasa, Zeyad; Chan, James; Siatskas, Christopher; Toh, Ban-Hock; Alderuccio, Frank

    2011-05-01

    Haematopoietic stem cell (HSC) transfer coupled with gene therapy is a powerful approach to treating fatal diseases such as X-linked severe combined immunodeficiency. This ability to isolate and genetically manipulate HSCs also offers a strategy for inducing immune tolerance through ectopic expression of autoantigens. We have previously shown that retroviral transduction of bone marrow (BM) with vectors encoding the autoantigen, myelin oligodendrocyte glycoprotein (MOG), can prevent the induction of experimental autoimmune encephalomyelitis (EAE). However, ubiquitous cellular expression of autoantigen driven by retroviral promoters may not be the best approach for clinical translation and a targeted expression approach may be more acceptable. As BM-derived dendritic cells (DCs) play a major role in tolerance induction, we asked whether targeted expression of MOG, a target autoantigen in EAE, to DCs can promote tolerance induction and influence the development of EAE. Self-inactivating retroviral vectors incorporating the mouse CD11c promoter were generated and used to transduce mouse BM cells. Transplantation of gene-modified cells into irradiated recipients resulted in the generation of chimeric mice with transgene expression limited to DCs. Notably, chimeric mice transplanted with MOG-expressing BM cells manifest a significant delay in the development of EAE suggesting that targeted antigen expression to tolerogenic cell types may be a feasible approach to inducing antigen-specific tolerance.

  18. Magnetic confinement system using charged ammonia targets

    DOEpatents

    Porter, Gary D.; Bogdanoff, Anatoly

    1979-01-01

    A system for guiding charged laser targets to a predetermined focal spot of a laser along generally arbitrary, and especially horizontal, directions which comprises a series of electrostatic sensors which provide inputs to a computer for real time calculation of position, velocity, and direction of the target along an initial injection trajectory, and a set of electrostatic deflection means, energized according to a calculated output of said computer, to change the target trajectory to intercept the focal spot of the laser which is triggered so as to illuminate the target of the focal spot.

  19. The CRISPR/Cas9 system produces specific and homozygous targeted gene editing in rice in one generation.

    PubMed

    Zhang, Hui; Zhang, Jinshan; Wei, Pengliang; Zhang, Botao; Gou, Feng; Feng, Zhengyan; Mao, Yanfei; Yang, Lan; Zhang, Heng; Xu, Nanfei; Zhu, Jian-Kang

    2014-08-01

    The CRISPR/Cas9 system has been demonstrated to efficiently induce targeted gene editing in a variety of organisms including plants. Recent work showed that CRISPR/Cas9-induced gene mutations in Arabidopsis were mostly somatic mutations in the early generation, although some mutations could be stably inherited in later generations. However, it remains unclear whether this system will work similarly in crops such as rice. In this study, we tested in two rice subspecies 11 target genes for their amenability to CRISPR/Cas9-induced editing and determined the patterns, specificity and heritability of the gene modifications. Analysis of the genotypes and frequency of edited genes in the first generation of transformed plants (T0) showed that the CRISPR/Cas9 system was highly efficient in rice, with target genes edited in nearly half of the transformed embryogenic cells before their first cell division. Homozygotes of edited target genes were readily found in T0 plants. The gene mutations were passed to the next generation (T1) following classic Mendelian law, without any detectable new mutation or reversion. Even with extensive searches including whole genome resequencing, we could not find any evidence of large-scale off-targeting in rice for any of the many targets tested in this study. By specifically sequencing the putative off-target sites of a large number of T0 plants, low-frequency mutations were found in only one off-target site where the sequence had 1-bp difference from the intended target. Overall, the data in this study point to the CRISPR/Cas9 system being a powerful tool in crop genome engineering. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

  20. Hitting the Target: Target Setting and Information Systems for the Learning and Skills Sector.

    ERIC Educational Resources Information Center

    Owen, Jane; Alterman, Jeff

    The use of target setting in conjunction with good information systems in colleges and work-based learning (WBL) providers can lead to improved service provisions across the sector in the United Kingdom. Target setting must be carried out in a systematic way in which providers must develop target- setting processes with a focus on learner success;…

  1. Scene-based nonuniformity correction for airborne point target detection systems.

    PubMed

    Zhou, Dabiao; Wang, Dejiang; Huo, Lijun; Liu, Rang; Jia, Ping

    2017-06-26

    Images acquired by airborne infrared search and track (IRST) systems are often characterized by nonuniform noise. In this paper, a scene-based nonuniformity correction method for infrared focal-plane arrays (FPAs) is proposed based on the constant statistics of the received radiation ratios of adjacent pixels. The gain of each pixel is computed recursively based on the ratios between adjacent pixels, which are estimated through a median operation. Then, an elaborate mathematical model describing the error propagation, derived from random noise and the recursive calculation procedure, is established. The proposed method maintains the characteristics of traditional methods in calibrating the whole electro-optics chain, in compensating for temporal drifts, and in not preserving the radiometric accuracy of the system. Moreover, the proposed method is robust since the frame number is the only variant, and is suitable for real-time applications owing to its low computational complexity and simplicity of implementation. The experimental results, on different scenes from a proof-of-concept point target detection system with a long-wave Sofradir FPA, demonstrate the compelling performance of the proposed method.

  2. Experimental new automatic tools for robotic stereotactic neurosurgery: towards "no hands" procedure of leads implantation into a brain target.

    PubMed

    Mazzone, P; Arena, P; Cantelli, L; Spampinato, G; Sposato, S; Cozzolino, S; Demarinis, P; Muscato, G

    2016-07-01

    The use of robotics in neurosurgery and, particularly, in stereotactic neurosurgery, is becoming more and more adopted because of the great advantages that it offers. Robotic manipulators easily allow to achieve great precision, reliability, and rapidity in the positioning of surgical instruments or devices in the brain. The aim of this work was to experimentally verify a fully automatic "no hands" surgical procedure. The integration of neuroimaging to data for planning the surgery, followed by application of new specific surgical tools, permitted the realization of a fully automated robotic implantation of leads in brain targets. An anthropomorphic commercial manipulator was utilized. In a preliminary phase, a software to plan surgery was developed, and the surgical tools were tested first during a simulation and then on a skull mock-up. In such a way, several tools were developed and tested, and the basis for an innovative surgical procedure arose. The final experimentation was carried out on anesthetized "large white" pigs. The determination of stereotactic parameters for the correct planning to reach the intended target was performed with the same technique currently employed in human stereotactic neurosurgery, and the robotic system revealed to be reliable and precise in reaching the target. The results of this work strengthen the possibility that a neurosurgeon may be substituted by a machine, and may represent the beginning of a new approach in the current clinical practice. Moreover, this possibility may have a great impact not only on stereotactic functional procedures but also on the entire domain of neurosurgery.

  3. Statistical Modeling of Single Target Cell Encapsulation

    PubMed Central

    Moon, SangJun; Ceyhan, Elvan; Gurkan, Umut Atakan; Demirci, Utkan

    2011-01-01

    High throughput drop-on-demand systems for separation and encapsulation of individual target cells from heterogeneous mixtures of multiple cell types is an emerging method in biotechnology that has broad applications in tissue engineering and regenerative medicine, genomics, and cryobiology. However, cell encapsulation in droplets is a random process that is hard to control. Statistical models can provide an understanding of the underlying processes and estimation of the relevant parameters, and enable reliable and repeatable control over the encapsulation of cells in droplets during the isolation process with high confidence level. We have modeled and experimentally verified a microdroplet-based cell encapsulation process for various combinations of cell loading and target cell concentrations. Here, we explain theoretically and validate experimentally a model to isolate and pattern single target cells from heterogeneous mixtures without using complex peripheral systems. PMID:21814548

  4. Revealing the Effects of the Herbal Pair of Euphorbia kansui and Glycyrrhiza on Hepatocellular Carcinoma Ascites with Integrating Network Target Analysis and Experimental Validation

    PubMed Central

    Zhang, Yanqiong; Lin, Ya; Zhao, Haiyu; Guo, Qiuyan; Yan, Chen; Lin, Na

    2016-01-01

    Although the herbal pair of Euphorbia kansui (GS) and Glycyrrhiza (GC) is one of the so-called "eighteen antagonistic medicaments" in Chinese medicinal literature, it is prescribed in a classic Traditional Chinese Medicine (TCM) formula Gansui-Banxia-Tang for cancerous ascites, suggesting that GS and GC may exhibit synergistic or antagonistic effects in different combination designs. Here, we modeled the effects of GS/GC combination with a target interaction network and clarified the associations between the network topologies involving the drug targets and the drug combination effects. Moreover, the "edge-betweenness" values, which is defined as the frequency with which edges are placed on the shortest paths between all pairs of modules in network, were calculated, and the ADRB1-PIK3CG interaction exhibited the greatest edge-betweenness value, suggesting its crucial role in connecting the other edges in the network. Because ADRB1 and PIK3CG were putative targets of GS and GC, respectively, and both had functional interactions with AVPR2 approved as known therapeutic target for ascites, we proposed that the ADRB1-PIK3CG-AVPR2 signal axis might be involved in the effects of the GS-GC combination on ascites. This proposal was further experimentally validated in a H22 hepatocellular carcinoma (HCC) ascites model. Collectively, this systems-level investigation integrated drug target prediction and network analysis to reveal the combination principles of the herbal pair of GS and GC. Experimental validation in an in vivo system provided convincing evidence that different combination designs of GS and GC might result in synergistic or antagonistic effects on HCC ascites that might be partially related to their regulation of the ADRB1-PIK3CG-AVPR2 signal axis. PMID:27143956

  5. Systems genetics for drug target discovery

    PubMed Central

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

    2011-01-01

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

  6. Experimental system for measurement of radiologists' performance by visual search task.

    PubMed

    Maeda, Eriko; Yoshikawa, Takeharu; Nakashima, Ryoichi; Kobayashi, Kazufumi; Yokosawa, Kazuhiko; Hayashi, Naoto; Masutani, Yoshitaka; Yoshioka, Naoki; Akahane, Masaaki; Ohtomo, Kuni

    2013-01-01

    Detective performance of radiologists for "obvious" targets should be evaluated by visual search task instead of ROC analysis, but visual task have not been applied to radiology studies. The aim of this study was to set up an environment that allows visual search task in radiology, to evaluate its feasibility, and to preliminarily investigate the effect of career on the performance. In a darkroom, ten radiologists were asked to answer the type of lesion by pressing buttons, when images without lesions, with bulla, ground-glass nodule, and solid nodule were randomly presented on a display. Differences in accuracy and reaction times depending on board certification were investigated. The visual search task was successfully and feasibly performed. Radiologists were found to have high sensitivity, specificity, positive predictive values and negative predictive values in non-board and board groups. Reaction time was under 1 second for all target types in both groups. Board radiologists were significantly faster in answering for bulla, but there were no significant differences for other targets and values. We developed an experimental system that allows visual search experiment in radiology. Reaction time for detection of bulla was shortened with experience.

  7. Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats.

    PubMed

    Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

    2016-01-01

    Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm.

  8. Recent Advances in Aptamers Targeting Immune System.

    PubMed

    Hu, Piao-Ping

    2017-02-01

    The immune system plays important role in protecting the organism by recognizing non-self molecules from pathogen such as bacteria, parasitic worms, and viruses. When the balance of the host defense system is disturbed, immunodeficiency, autoimmunity, and inflammation occur. Nucleic acid aptamers are short single-stranded DNA (ssDNA) or RNA ligands that interact with complementary molecules with high specificity and affinity. Aptamers that target the molecules involved in immune system to modulate their function have great potential to be explored as new diagnostic and therapeutic agents for immune disorders. This review summarizes recent advances in the development of aptamers targeting immune system. The selection of aptamers with superior chemical and biological characteristics will facilitate their application in the diagnosis and treatment of immune disorders.

  9. Rodent Models of Experimental Endometriosis: Identifying Mechanisms of Disease and Therapeutic Targets

    PubMed Central

    Bruner-Tran, Kaylon L.; Mokshagundam, Shilpa; Herington, Jennifer L.; Ding, Tianbing; Osteen, Kevin G.

    2018-01-01

    Background: Although it has been more than a century since endometriosis was initially described in the literature, understanding the etiology and natural history of the disease has been challenging. However, the broad utility of murine and rat models of experimental endometriosis has enabled the elucidation of a number of potentially targetable processes which may otherwise promote this disease. Objective: To review a variety of studies utilizing rodent models of endometriosis to illustrate their utility in examining mechanisms associated with development and progression of this disease. Results: Use of rodent models of endometriosis has provided a much broader understanding of the risk factors for the initial development of endometriosis, the cellular pathology of the disease and the identification of potential therapeutic targets. Conclusion: Although there are limitations with any animal model, the variety of experimental endometriosis models that have been developed has enabled investigation into numerous aspects of this disease. Thanks to these models, our under-standing of the early processes of disease development, the role of steroid responsiveness, inflammatory processes and the peritoneal environment has been advanced. More recent models have begun to shed light on how epigenetic alterations con-tribute to the molecular basis of this disease as well as the multiple comorbidities which plague many patients. Continued de-velopments of animal models which aid in unraveling the mechanisms of endometriosis development provide the best oppor-tunity to identify therapeutic strategies to prevent or regress this enigmatic disease.

  10. A method for detecting small targets based on cumulative weighted value of target properties

    NASA Astrophysics Data System (ADS)

    Jin, Xing; Sun, Gang; Wang, Wei-hua; Liu, Fang; Chen, Zeng-ping

    2015-03-01

    Laser detection based on the "cat's eye effect" has become the hot research project for its initiative compared to the passivity of sound detection and infrared detection. And the target detection is one of the core technologies in this system. The paper puts forward a method for detecting small targets based on cumulative weighted value of target properties using given data. Firstly, we make a frame difference to the images, then make image processing based on Morphology Principles. Secondly, we segment images, and screen the targets; then find some interesting locations. Finally, comparing to a quantity of frames, we locate the target. We did an exam to 394 true frames, the experimental result shows that the mathod can detect small targets efficiently.

  11. Targeting the Thioredoxin System for Cancer Therapy.

    PubMed

    Zhang, Junmin; Li, Xinming; Han, Xiao; Liu, Ruijuan; Fang, Jianguo

    2017-09-01

    Thioredoxin (Trx) and thioredoxin reductase (TrxR) are essential components of the Trx system which plays pivotal roles in regulating multiple cellular redox signaling pathways. In recent years TrxR/Trx have been increasingly recognized as an important modulator of tumor development, and hence targeting TrxR/Trx is a promising strategy for cancer treatment. In this review we first discuss the structural details of TrxR, the functions of the Trx system, and the rational of targeting TrxR/Trx for cancer treatment. We also highlight small-molecule TrxR/Trx inhibitors that have potential anticancer activity and review their mechanisms of action. Finally, we examine the challenges of developing TrxR/Trx inhibitors as anticancer agents and perspectives for selectively targeting TrxR/Trx. Copyright © 2017 Elsevier Ltd. All rights reserved.

  12. Finding off-targets, biological pathways, and target diseases for chymase inhibitors via structure-based systems biology approach.

    PubMed

    Arooj, Mahreen; Sakkiah, Sugunadevi; Cao, Guang Ping; Kim, Songmi; Arulalapperumal, Venkatesh; Lee, Keun Woo

    2015-07-01

    Off-target binding connotes the binding of a small molecule of therapeutic significance to a protein target in addition to the primary target for which it was proposed. Progressively such off-targeting is emerging to be regular practice to reveal side effects. Chymase is an enzyme of hydrolase class that catalyzes hydrolysis of peptide bonds. A link between heart failure and chymase is ascribed, and a chymase inhibitor is in clinical phase II for treatment of heart failure. However, the underlying mechanisms of the off-target effects of human chymase inhibitors are still unclear. Here, we develop a robust computational strategy that is applicable to any enzyme system and that allows the prediction of drug effects on biological processes. Putative off-targets for chymase inhibitors were identified through various structural and functional similarity analyses along with molecular docking studies. Finally, literature survey was performed to incorporate these off-targets into biological pathways and to establish links between pathways and particular adverse effects. Off-targets of chymase inhibitors are linked to various biological pathways such as classical and lectin pathways of complement system, intrinsic and extrinsic pathways of coagulation cascade, and fibrinolytic system. Tissue kallikreins, granzyme M, neutrophil elastase, and mesotrypsin are also identified as off-targets. These off-targets and their associated pathways are elucidated for the effects of inflammation, cancer, hemorrhage, thrombosis, and central nervous system diseases (Alzheimer's disease). Prospectively, our approach is helpful not only to better understand the mechanisms of chymase inhibitors but also for drug repurposing exercises to find novel uses for these inhibitors. © 2014 Wiley Periodicals, Inc.

  13. Tumor target amplification: Implications for nano drug delivery systems.

    PubMed

    Seidi, Khaled; Neubauer, Heidi A; Moriggl, Richard; Jahanban-Esfahlan, Rana; Javaheri, Tahereh

    2018-04-10

    Tumor cells overexpress surface markers which are absent from normal cells. These tumor-restricted antigenic signatures are a fundamental basis for distinguishing on-target from off-target cells for ligand-directed targeting of cancer cells. Unfortunately, tumor heterogeneity impedes the establishment of a solid expression pattern for a given target marker, leading to drastic changes in quality (availability) and quantity (number) of the target. Consequently, a subset of cancer cells remains untargeted during the course of treatment, which subsequently promotes drug-resistance and cancer relapse. Since target inefficiency is only problematic for cancer treatment and not for treatment of other pathological conditions such as viral/bacterial infections, target amplification or the generation of novel targets is key to providing eligible antigenic markers for effective targeted therapy. This review summarizes the limitations of current ligand-directed targeting strategies and provides a comprehensive overview of tumor target amplification strategies, including self-amplifying systems, dual targeting, artificial markers and peptide modification. We also discuss the therapeutic and diagnostic potential of these approaches, the underlying mechanism(s) and established methodologies, mostly in the context of different nanodelivery systems, to facilitate more effective ligand-directed cancer cell monitoring and targeting. Copyright © 2018 Elsevier B.V. All rights reserved.

  14. The challenges of modulating the 'rest and digest' system: acetylcholine receptors as drug targets.

    PubMed

    VanPatten, Sonya; Al-Abed, Yousef

    2017-01-01

    Acetylcholine, a major neurotransmitter of the parasympathetic and sympathetic nervous systems, was discovered in the early 1900s. Over the years, researchers have revealed much about its regulation, properties of its receptors and features of the downstream signaling that influence its terminal effects. The acetylcholine system, traditionally associated with neuromuscular communication, is now known to play a crucial part in modulation of the immune system and other 'rest and digest' effects. Recent research seeks to elucidate the system's role in brain functions including cognition, sleep, arousal, motivation, reward and pain. We highlight clinically approved and experimental drugs that modulate the acetylcholine receptors. The complexities in targeting the acetylcholine receptors are vast and finding future indications for drug development associated with specific acetylcholine receptors remains a challenge. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Target Soil Impact Verification: Experimental Testing and Kayenta Constitutive Modeling.

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

    Broome, Scott Thomas; Flint, Gregory Mark; Dewers, Thomas

    2015-11-01

    This report details experimental testing and constitutive modeling of sandy soil deformation under quasi - static conditions. This is driven by the need to understand constitutive response of soil to target/component behavior upon impact . An experimental and constitutive modeling program was followed to determine elastic - plastic properties and a compressional failure envelope of dry soil . One hydrostatic, one unconfined compressive stress (UCS), nine axisymmetric compression (ACS) , and one uniaxial strain (US) test were conducted at room temperature . Elastic moduli, assuming isotropy, are determined from unload/reload loops and final unloading for all tests pre - failuremore » and increase monotonically with mean stress. Very little modulus degradation was discernable from elastic results even when exposed to mean stresses above 200 MPa . The failure envelope and initial yield surface were determined from peak stresses and observed onset of plastic yielding from all test results. Soil elasto - plastic behavior is described using the Brannon et al. (2009) Kayenta constitutive model. As a validation exercise, the ACS - parameterized Kayenta model is used to predict response of the soil material under uniaxial strain loading. The resulting parameterized and validated Kayenta model is of high quality and suitable for modeling sandy soil deformation under a range of conditions, including that for impact prediction.« less

  16. Laser range profiling for small target recognition

    NASA Astrophysics Data System (ADS)

    Steinvall, Ove; Tulldahl, Michael

    2016-05-01

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

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

    PubMed

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

    2017-03-31

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

  18. Experimental investigation of a general real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring

    NASA Astrophysics Data System (ADS)

    Cho, Byungchul; Poulsen, Per; Ruan, Dan; Sawant, Amit; Keall, Paul J.

    2012-11-01

    The goal of this work was to experimentally quantify the geometric accuracy of a novel real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring for clinically realistic arc and static field treatment delivery and target motion conditions. A general method for real-time target localization using kV imaging and respiratory monitoring was developed. Each dimension of internal target motion T(x, y, z; t) was estimated from the external respiratory signal R(t) through the correlation between R(ti) and the projected marker positions p(xp, yp; ti) on kV images by a state-augmented linear model: T(x, y, z; t) = aR(t) + bR(t - τ) + c. The model parameters, a, b, c, were determined by minimizing the squared fitting error ∑‖p(xp, yp; ti) - P(θi) · (aR(ti) + bR(ti - τ) + c)‖2 with the projection operator P(θi). The model parameters were first initialized based on acquired kV arc images prior to MV beam delivery. This method was implemented on a trilogy linear accelerator consisting of an OBI x-ray imager (operating at 1 Hz) and real-time position monitoring (RPM) system (30 Hz). Arc and static field plans were delivered to a moving phantom programmed with measured lung tumour motion from ten patients. During delivery, the localization method determined the target position and the beam was adjusted in real time via dynamic multileaf collimator (DMLC) adaptation. The beam-target alignment error was quantified by segmenting the beam aperture and a phantom-embedded fiducial marker on MV images and analysing their relative position. With the localization method, the root-mean-squared errors of the ten lung tumour traces ranged from 0.7-1.3 mm and 0.8-1.4 mm during the single arc and five-field static beam delivery, respectively. Without the localization method, these errors ranged from 3.1-7.3 mm. In summary, a general method for real-time target localization using kV imaging and respiratory monitoring has been

  19. Nanoparticles Effectively Target Rapamycin Delivery to Sites of Experimental Aortic Aneurysm in Rats

    PubMed Central

    Shirasu, Takuro; Koyama, Hiroyuki; Miura, Yutaka; Hoshina, Katsuyuki; Kataoka, Kazunori; Watanabe, Toshiaki

    2016-01-01

    Several drugs targeting the pathogenesis of aortic aneurysm have shown efficacy in model systems but not in clinical trials, potentially owing to the lack of targeted drug delivery. Here, we designed a novel drug delivery system using nanoparticles to target the disrupted aortic aneurysm micro-structure. We generated poly(ethylene glycol)-shelled nanoparticles incorporating rapamycin that exhibited uniform diameter and long-term stability. When injected intravenously into a rat model in which abdominal aortic aneurysm (AAA) had been induced by infusing elastase, labeled rapamycin nanoparticles specifically accumulated in the AAA. Microscopic analysis revealed that rapamycin nanoparticles were mainly distributed in the media and adventitia where the wall structures were damaged. Co-localization of rapamycin nanoparticles with macrophages was also noted. Rapamycin nanoparticles injected during the process of AAA formation evinced significant suppression of AAA formation and mural inflammation at 7 days after elastase infusion, as compared with rapamycin treatment alone. Correspondingly, the activities of matrix metalloproteinases and the expression of inflammatory cytokines were significantly suppressed by rapamycin nanoparticle treatment. Our findings suggest that the nanoparticle-based delivery system achieves specific delivery of rapamycin to the rat AAA and might contribute to establishing a drug therapy approach targeting aortic aneurysm. PMID:27336852

  20. Faster experimental validation of microRNA targets using cold fusion cloning and a dual firefly-Renilla luciferase reporter assay.

    PubMed

    Alvarez, M Lucrecia

    2014-01-01

    Different target prediction algorithms have been developed to provide a list of candidate target genes for a given animal microRNAs (miRNAs). However, these computational approaches provide both false-positive and false-negative predictions. Therefore, the target genes of a specific miRNA identified in silico should be experimentally validated. In this chapter, we describe a step-by-step protocol for the experimental validation of a direct miRNA target using a faster Dual Firefly-Renilla Luciferase Reporter Assay. We describe how to construct reporter plasmids using the simple, fast, and highly efficient cold fusion cloning technology, which does not require ligase, phosphatase, or restriction enzymes. In addition, we provide a protocol for co-transfection of reporter plasmids with either miRNA mimics or miRNA inhibitors in human embryonic kidney 293 (HEK293) cells, as well as a description on how to measure Firefly and Renilla luciferase activity using the Dual-Glo Luciferase Assay kit. As an example of the use of this technology, we will validate glucose-6-phosphate dehydrogenase (G6PD) as a direct target of miR-1207-5p.

  1. Fe₃O₄ Nanoparticles in Targeted Drug/Gene Delivery Systems.

    PubMed

    Shen, Lazhen; Li, Bei; Qiao, Yongsheng

    2018-02-23

    Fe₃O₄ nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe₃O₄ NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe₃O₄ NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe₃O₄ NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe₃O₄ NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe₃O₄ NPs targeting drug/gene delivery systems.

  2. Target tracking system based on preliminary and precise two-stage compound cameras

    NASA Astrophysics Data System (ADS)

    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.

  3. Curriculum system for experimental teaching in optoelectronic information

    NASA Astrophysics Data System (ADS)

    Di, Hongwei; Chen, Zhenqiang; Zhang, Jun; Luo, Yunhan

    2017-08-01

    The experimental curriculum system is directly related to talent training quality. Based on the careful investigation of the developing request of the optoelectronic information talents in the new century, the experimental teaching goal and the content, the teaching goal was set to cultivate students' innovative consciousness, innovative thinking, creativity and problem solving ability. Through straightening out the correlation among the experimental teaching in the main courses, the whole structure design was phased out, as well as the hierarchical curriculum connotation. According to the ideas of "basic, comprehensive, applied and innovative", the construction of experimental teaching system called "triple-three" was put forward for the optoelectronic information experimental teaching practice.

  4. Forming Uniform Deuterium-Ice Layers in Cryogenic Targets: Experiences Using the OMEGA Cryogenic Target Handling System

    NASA Astrophysics Data System (ADS)

    Harding, D. R.; Wittman, M. D.; Elasky, L.; Iwan, L. S.; Lund, L.

    2001-10-01

    The OMEGA Cryogenic Target Handling System (OCTHS) allows variable-thickness ice layers (nominal 100-μm) to be formed inside OMEGA-size (1-mm-diam., 3-μm-wall) plastic shells. The OCTHS design provides the most straightforward thermal environment for layering targets: permeation filled spherical targets are in a spherical isothermal environment. The layered target can be rotated 360^o to acquire multiple views of the ice layer. However, the capability of providing cryogenic targets for implosion experiments imposes constraints that do not exist in test systems dedicated to ice-layering studies. Most affected is the ability to characterize the target: space constraints and the need for multiple sets of windows limit the viewing access to f/5 optics, which affects the image quality. With these features, the OCTS provides the most relevant test system, to date, for layering targets and quantifying the overall ice roughness. No single layering protocol provides repeatable ice smoothness. All techniques require extensive operator interaction, and the layering process is lengthy. Typical ice rms smoothness varied from 5 to 10 μm for all targets studied. Characterizing the ice layer from different views shows a ~30% variation in the ice rms smoothness and a greater difference in the power spectra, depending on the view axis. This work was supported by the U.S. DOE Office of Inertial Confinement Fusion under Cooperative Agreement No. DE-FC03-92SF19460.

  5. Radiation effects in IFMIF Li target diagnostic systems

    NASA Astrophysics Data System (ADS)

    Molla, J.; Vila, R.; Shikama, T.; Horiike, H.; Simakov, S.; Ciotti, M.; Ibarra, A.

    2009-04-01

    Diagnostics for the lithium target will be crucial for the operation of IFMIF. Several parameters as the lithium temperature, target thickness or wave pattern must be monitored during operation. Radiation effects may produce malfunctioning in any of these diagnostics due to the exposure to high radiation fields. The main diagnostic systems proposed for the operation of IFMIF are reviewed in this paper from the point of view of radiation damage. The main tools for the assessment of the performance of these diagnostics are the neutronics calculations by using specialised codes and the information accumulated during the last decades on the radiation effects in functional materials, components and diagnostics for ITER. This analysis allows to conclude that the design of some of the diagnostic systems must be revised to assure the high availability required for the target system.

  6. Target discrimination strategies in optics detection

    NASA Astrophysics Data System (ADS)

    Sjöqvist, Lars; Allard, Lars; Henriksson, Markus; Jonsson, Per; Pettersson, Magnus

    2013-10-01

    Detection and localisation of optical assemblies used for weapon guidance or sniper rifle scopes has attracted interest for security and military applications. Typically a laser system is used to interrogate a scene of interest and the retro-reflected radiation is detected. Different system approaches for area coverage can be realised ranging from flood illumination to step-and-stare or continuous scanning schemes. Independently of the chosen approach target discrimination is a crucial issue, particularly if a complex scene such as in an urban environment and autonomous operation is considered. In this work target discrimination strategies in optics detection are discussed. Typical parameters affecting the reflected laser radiation from the target are the wavelength, polarisation properties, temporal effects and the range resolution. Knowledge about the target characteristics is important to predict the target discrimination capability. Two different systems were used to investigate polarisation properties and range resolution information from targets including e.g. road signs, optical reflexes, rifle sights and optical references. The experimental results and implications on target discrimination will be discussed. If autonomous operation is required target discrimination becomes critical in order to reduce the number of false alarms.

  7. A novel double-targeted nondrug delivery system for targeting cancer stem cells

    PubMed Central

    Qiao, Shupei; Zhao, Yufang; Geng, Shuai; Li, Yong; Hou, Xiaolu; Liu, Yi; Lin, Feng-Huei; Yao, Lifen; Tian, Weiming

    2016-01-01

    Instead of killing cancer stem cells (CSCs), the conventional chemotherapy used for cancer treatment promotes the enrichment of CSCs, which are responsible for tumor growth, metastasis, and recurrence. However, most therapeutic agents are only able to kill a small proportion of CSCs by targeting one or two cell surface markers or dysregulated CSC pathways, which are usually shared with normal stem cells (NSCs). In this study, we developed a novel nondrug delivery system for the dual targeting of CSCs by conjugating hyaluronic acid (HA) and grafting the doublecortin-like kinase 1 (DCLK1) monoclonal antibody to the surface of poly(ethylene glycol) (PEG)–poly(d,l-lactide-co-glycolide) (PLGA) nanoparticles (NPs), which can specifically target CD44 receptors and the DCLK1 surface marker – the latter was shown to possess the capacity to distinguish between CSCSs and NSCs. The size and morphology of these NPs were characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). This was followed by studies of NP encapsulation efficiency and in vitro drug release properties. Then, the cytotoxicity of the NPs was tested via Cell Counting Kit-8 assay. Finally, the 4T1 CSCs were obtained from the alginate-based platform, which we developed as an in vitro tumor model. Tumor-bearing nude mice were used as in vivo models to systematically detect the ability of NPs to target CSCs. Our results showed that the DCLK1–HA–PEG–PLGA NPs exhibited a targeting effect toward CSCs both in vitro and in vivo. These findings have important implications for the rational design of drug delivery systems that target CSCs with high efficacy. PMID:27994463

  8. Analysis of discriminants for experimental 3D SAR imagery of human targets

    NASA Astrophysics Data System (ADS)

    Chan, Brigitte; Sévigny, Pascale; DiFilippo, David D. J.

    2014-10-01

    Development of a prototype 3-D through-wall synthetic aperture radar (SAR) system is currently underway at Defence Research and Development Canada. The intent is to map out building wall layouts and to detect targets of interest and their location behind walls such as humans, arms caches, and furniture. This situational awareness capability can be invaluable to the military working in an urban environment. Tools and algorithms are being developed to exploit the resulting 3-D imagery. Current work involves analyzing signatures of targets behind a wall and understanding the clutter and multipath signals in a room of interest. In this paper, a comprehensive study of 3-D human target signature metrics in free space is presented. The aim is to identify features for discrimination of the human target from other targets. Targets used in this investigation include a human standing, a human standing with arms stretched out, a chair, a table, and a metallic plate. Several features were investigated as potential discriminants and five which were identified as good candidates are presented in this paper. Based on this study, no single feature could be used to fully discriminate the human targets from all others. A combination of at least two different features is required to achieve this.

  9. Targeting CD6 for the treatment of experimental autoimmune uveitis.

    PubMed

    Zhang, Lingjun; Li, Yan; Qiu, Wen; Bell, Brent A; Dvorina, Nina; Baldwin, William M; Singer, Nora; Kern, Timothy; Caspi, Rachel R; Fox, David A; Lin, Feng

    2018-06-01

    CD6 is emerging as a new target for treating many pathological conditions in which T cells are integrally involved, but even the latest data from studies of CD6 gene engineered mice were still contradictory. To address this issue, we studied experimental autoimmune uveitis (EAU), a model of autoimmune uveitis, in wild-type (WT) and CD6 knockout (KO) mice. After EAU induction in WT and CD6 KO mice, we evaluated ocular inflammation and compared retinal antigen-specific T-cell responses using scanning laser ophthalmoscopy, spectral-domain optical coherence tomography, histopathology, and T cell recall assays. Uveitogenic T cells from WT and CD6 KO mice were adoptively transferred into WT naïve mice to confirm the impact of CD6 on T cells. In addition, we immunized CD6 KO mice with recombinant CD6 protein to develop mouse anti-mouse CD6 monoclonal antibodies (mAbs) in which functional antibodies exhibiting cross-reactivity with human CD6 were screened and identified for treatment studies. In CD6 KO mice with EAU, we found significantly decreased retinal inflammation and reduced autoreactive T-cell responses, and confirmed the impaired uveitogenic capacity of T cells from these mice in an adoptive transfer experiment. Notably, one of these cross-reactive mAbs significantly ameliorated retinal inflammation in EAU induced by the adoptive transfer of uveitogenic T cells. Together, these data strongly suggest that CD6 plays a previously unknown, but pivotal role in autoimmune uveitis, and may be a promising new treatment target for this blinding disease. In addition, the newly developed mouse anti-mouse/human CD6 mAbs could be valuable tools for testing CD6-targeted therapies in other mouse models of human diseases. Copyright © 2018 Elsevier Ltd. All rights reserved.

  10. Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting.

    PubMed

    Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D

    2017-04-07

    Bacterial CRISPR-Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR-Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR-Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification.

  11. Targeted activation of diverse CRISPR-Cas systems for mammalian genome editing via proximal CRISPR targeting

    PubMed Central

    Chen, Fuqiang; Ding, Xiao; Feng, Yongmei; Seebeck, Timothy; Jiang, Yanfang; Davis, Gregory D.

    2017-01-01

    Bacterial CRISPR–Cas systems comprise diverse effector endonucleases with different targeting ranges, specificities and enzymatic properties, but many of them are inactive in mammalian cells and are thus precluded from genome-editing applications. Here we show that the type II-B FnCas9 from Francisella novicida possesses novel properties, but its nuclease function is frequently inhibited at many genomic loci in living human cells. Moreover, we develop a proximal CRISPR (termed proxy-CRISPR) targeting method that restores FnCas9 nuclease activity in a target-specific manner. We further demonstrate that this proxy-CRISPR strategy is applicable to diverse CRISPR–Cas systems, including type II-C Cas9 and type V Cpf1 systems, and can facilitate precise gene editing even between identical genomic sites within the same genome. Our findings provide a novel strategy to enable use of diverse otherwise inactive CRISPR–Cas systems for genome-editing applications and a potential path to modulate the impact of chromatin microenvironments on genome modification. PMID:28387220

  12. IGF system targeted therapy: Therapeutic opportunities for ovarian cancer.

    PubMed

    Liefers-Visser, J A L; Meijering, R A M; Reyners, A K L; van der Zee, A G J; de Jong, S

    2017-11-01

    The insulin-like growth factor (IGF) system comprises multiple growth factor receptors, including insulin-like growth factor 1 receptor (IGF-1R), insulin receptor (IR) -A and -B. These receptors are activated upon binding to their respective growth factor ligands, IGF-I, IGF-II and insulin, and play an important role in development, maintenance, progression, survival and chemotherapeutic response of ovarian cancer. In many pre-clinical studies anti-IGF-1R/IR targeted strategies proved effective in reducing growth of ovarian cancer models. In addition, anti-IGF-1R targeted strategies potentiated the efficacy of platinum based chemotherapy. Despite the vast amount of encouraging and promising pre-clinical data, anti-IGF-1R/IR targeted strategies lacked efficacy in the clinic. The question is whether targeting the IGF-1R/IR signaling pathway still holds therapeutic potential. In this review we address the complexity of the IGF-1R/IR signaling pathway, including receptor heterodimerization within and outside the IGF system and downstream signaling. Further, we discuss the implications of this complexity on current targeted strategies and indicate therapeutic opportunities for successful targeting of the IGF-1R/IR signaling pathway in ovarian cancer. Multiple-targeted approaches circumventing bidirectional receptor tyrosine kinase (RTK) compensation and prevention of system rewiring are expected to have more therapeutic potential. Copyright © 2017 The Author(s). Published by Elsevier Ltd.. All rights reserved.

  13. Prioritized System Science Targets for Heliophysics

    NASA Astrophysics Data System (ADS)

    Spann, J. F.; Christensen, A. B.; St Cyr, O. C.; Posner, A.; Giles, B. L.

    2009-12-01

    Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun’s explosive energy output creates complicated field and plasma structures that when coupled with our terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. This immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

  14. Prioritized System Science Targets for Heliophysics

    NASA Technical Reports Server (NTRS)

    Spann, James Frederick; Christensen, Andrew B.; SaintCyr, Orville Chris; Posner, Arik; Giles, Barbara L.

    2009-01-01

    Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun's explosive energy output creates complicated field and plasma structures that when coupled with our terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. This immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

  15. Customer systems group 1996 target summaries: Information systems and telecommunications. Revision 4

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

    NONE

    1995-06-15

    The target summaries give planning information on the new business systems development; customer service applications and infrastructure; and advanced information systems and telecommunications research, architecture and standards factions of Information Systems & Telecommunications.

  16. Strategies for systemic radiotherapy of micrometastases using antibody-targeted 131I.

    PubMed

    Wheldon, T E; O'Donoghue, J A; Hilditch, T E; Barrett, A

    1988-02-01

    A simple analysis is developed to evaluate the likely effectiveness of treatment of micrometastases by antibody-targeted 131I. Account is taken of the low levels of tumour uptake of antibody-conjugated 131I presently achievable and of the "energy wastage" in targeting microscopic tumours with a radionuclide whose disintegration energy is widely dissipated. The analysis shows that only modest doses can be delivered to micrometastases when total body dose is restricted to levels which allow recovery of bone marrow. Much higher doses could be delivered to micrometastases when bone marrow rescue is used. A rationale is presented for targeted systemic radiotherapy used in combination with external beam total body irradiation (TBI) and bone marrow rescue. This has some practical advantages. The effect of the targeted component is to impose a biological non-uniformity on the total body dose distribution with regions of high tumour cell density receiving higher doses. Where targeting results in high doses to particular normal organs (e.g. liver, kidney) the total dose to these organs could be kept within tolerable limits by appropriate shielding of the external beam radiation component of the treatment. Greater levels of tumour cell kill should be achievable by the combination regime without any increase in normal tissue damage over that inflicted by conventional TBI. The predicted superiority of the combination regime is especially marked for tumours just below the threshold for detectability (e.g. approximately 1 mm-1 cm diameter). This approach has the advantage that targeted radiotherapy provides only a proportion of the total body dose, most of which is given by a familiar technique. The proportion of dose given by the targeted component could be increased as experience is gained. The predicted superiority of the combination strategy should be experimentally testable using laboratory animals. Clinical applications should be cautiously approached, with due regard to

  17. GUIDE-0: An Experimental Information System.

    ERIC Educational Resources Information Center

    Murai, Shinnichi

    A description is provided of GUIDE-0, an experimental information system. The system serves as a bibliographic aid for students who are taking introductory computer science courses whose material is at least partially implemented via PLATO-IV lessons. Following a brief introduction to the system in Chapter I, the second Chapter describes the…

  18. Targeting miR-155 to Treat Experimental Scleroderma.

    PubMed

    Yan, Qingran; Chen, Jie; Li, Wei; Bao, Chunde; Fu, Qiong

    2016-02-01

    Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155(-/-) mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications.

  19. Targeting miR-155 to Treat Experimental Scleroderma

    PubMed Central

    Yan, Qingran; Chen, Jie; Li, Wei; Bao, Chunde; Fu, Qiong

    2016-01-01

    Scleroderma is a refractory autoimmune skin fibrotic disorder. Alterations of microRNAs in lesional skin could be a new approach to treating the disease. Here, we found that expression of miR-155 was up regulated in lesional skin tissue from patients with either systemic or localized scleroderma, and correlated with fibrosis area. Then we demonstrated the potential of miR-155 as a therapeutic target in pre-clinical scleroderma models. MiR-155−/− mice were resistant to bleomycin induced skin fibrosis. Moreover, topical antagomiR-155 could effectively treat mice primed with subcutaneous bleomycin. In primary skin fibroblast, miR-155 silencing could inhibit collagen synthesis function, as well as signaling intensity of two pro-fibrotic pathways, Wnt/β-catenin and Akt, simultaneously. We further showed that miR-155 could regulate the two pathways via directly targeting casein kinase 1α (CK1α) and Src homology 2-containing inositol phosphatase-1 (SHIP-1), as previous reports. Mice with miR-155 knockout or topical antagomir-155 treatment showed inhibited Wnt/β-catenin and Akt signaling in skin upon bleomycin challenge. Together, our data suggest the potential of miR-155 silencing as a promising treatment for dermal fibrosis, especially in topical applications. PMID:26828700

  20. An Accurate and Fault-Tolerant Target Positioning System for Buildings Using Laser Rangefinders and Low-Cost MEMS-Based MARG Sensors

    PubMed Central

    Zhao, Lin; Guan, Dongxue; Landry, René Jr.; Cheng, Jianhua; Sydorenko, Kostyantyn

    2015-01-01

    Target positioning systems based on MEMS gyros and laser rangefinders (LRs) have extensive prospects due to their advantages of low cost, small size and easy realization. The target positioning accuracy is mainly determined by the LR’s attitude derived by the gyros. However, the attitude error is large due to the inherent noises from isolated MEMS gyros. In this paper, both accelerometer/magnetometer and LR attitude aiding systems are introduced to aid MEMS gyros. A no-reset Federated Kalman Filter (FKF) is employed, which consists of two local Kalman Filters (KF) and a Master Filter (MF). The local KFs are designed by using the Direction Cosine Matrix (DCM)-based dynamic equations and the measurements from the two aiding systems. The KFs can estimate the attitude simultaneously to limit the attitude errors resulting from the gyros. Then, the MF fuses the redundant attitude estimates to yield globally optimal estimates. Simulation and experimental results demonstrate that the FKF-based system can improve the target positioning accuracy effectively and allow for good fault-tolerant capability. PMID:26512672

  1. Neural Network Target Identification System for False Alarm Reduction

    NASA Technical Reports Server (NTRS)

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

    2009-01-01

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

  2. Experimental evaluation of penetration capabilities of a Geiger-mode APD array laser radar system

    NASA Astrophysics Data System (ADS)

    Jonsson, Per; Tulldahl, Michael; Hedborg, Julia; Henriksson, Markus; Sjöqvist, Lars

    2017-10-01

    Laser radar 3D imaging has the potential to improve target recognition in many scenarios. One case that is challenging for most optical sensors is to recognize targets hidden in vegetation or behind camouflage. The range resolution of timeof- flight 3D sensors allows segmentation of obscuration and target if the surfaces are separated far enough so that they can be resolved as two distances. Systems based on time-correlated single-photon counting (TCSPC) have the potential to resolve surfaces closer to each other compared to laser radar systems based on proportional mode detection technologies and is therefore especially interesting. Photon counting detection is commonly performed with Geigermode Avalanche Photodiodes (GmAPD) that have the disadvantage that they can only detect one photon per laser pulse per pixel. A strong return from an obscuring object may saturate the detector and thus limit the possibility to detect the hidden target even if photons from the target reach the detector. The operational range where good foliage penetration is observed is therefore relatively narrow for GmAPD systems. In this paper we investigate the penetration capability through semi-transparent surfaces for a laser radar with a 128×32 pixel GmAPD array and a 1542 nm wavelength laser operating at a pulse repetition frequency of 90 kHz. In the evaluation a screen was placed behind different canvases with varying transmissions and the detected signals from the surfaces for different laser intensities were measured. The maximum return from the second surface occurs when the total detection probability is around 0.65-0.75 per pulse. At higher laser excitation power the signal from the second surface decreases. To optimize the foliage penetration capability it is thus necessary to adaptively control the laser power to keep the returned signal within this region. In addition to the experimental results, simulations to study the influence of the pulse energy on penetration through

  3. Experimental investigation of a general real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring.

    PubMed

    Cho, Byungchul; Poulsen, Per; Ruan, Dan; Sawant, Amit; Keall, Paul J

    2012-11-21

    The goal of this work was to experimentally quantify the geometric accuracy of a novel real-time 3D target localization method using sequential kV imaging combined with respiratory monitoring for clinically realistic arc and static field treatment delivery and target motion conditions. A general method for real-time target localization using kV imaging and respiratory monitoring was developed. Each dimension of internal target motion T(x, y, z; t) was estimated from the external respiratory signal R(t) through the correlation between R(t(i)) and the projected marker positions p(x(p), y(p); t(i)) on kV images by a state-augmented linear model: T(x, y, z; t) = aR(t) + bR(t - τ) + c. The model parameters, a, b, c, were determined by minimizing the squared fitting error ∑‖p(x(p), y(p); t(i)) - P(θ(i)) · (aR(t(i)) + bR(t(i) - τ) + c)‖(2) with the projection operator P(θ(i)). The model parameters were first initialized based on acquired kV arc images prior to MV beam delivery. This method was implemented on a trilogy linear accelerator consisting of an OBI x-ray imager (operating at 1 Hz) and real-time position monitoring (RPM) system (30 Hz). Arc and static field plans were delivered to a moving phantom programmed with measured lung tumour motion from ten patients. During delivery, the localization method determined the target position and the beam was adjusted in real time via dynamic multileaf collimator (DMLC) adaptation. The beam-target alignment error was quantified by segmenting the beam aperture and a phantom-embedded fiducial marker on MV images and analysing their relative position. With the localization method, the root-mean-squared errors of the ten lung tumour traces ranged from 0.7-1.3 mm and 0.8-1.4 mm during the single arc and five-field static beam delivery, respectively. Without the localization method, these errors ranged from 3.1-7.3 mm. In summary, a general method for real-time target localization using kV imaging and respiratory

  4. Infrared dim and small target detecting and tracking method inspired by Human Visual System

    NASA Astrophysics Data System (ADS)

    Dong, Xiabin; Huang, Xinsheng; Zheng, Yongbin; Shen, Lurong; Bai, Shengjian

    2014-01-01

    Detecting and tracking dim and small target in infrared images and videos is one of the most important techniques in many computer vision applications, such as video surveillance and infrared imaging precise guidance. Recently, more and more algorithms based on Human Visual System (HVS) have been proposed to detect and track the infrared dim and small target. In general, HVS concerns at least three mechanisms including contrast mechanism, visual attention and eye movement. However, most of the existing algorithms simulate only a single one of the HVS mechanisms, resulting in many drawbacks of these algorithms. A novel method which combines the three mechanisms of HVS is proposed in this paper. First, a group of Difference of Gaussians (DOG) filters which simulate the contrast mechanism are used to filter the input image. Second, a visual attention, which is simulated by a Gaussian window, is added at a point near the target in order to further enhance the dim small target. This point is named as the attention point. Eventually, the Proportional-Integral-Derivative (PID) algorithm is first introduced to predict the attention point of the next frame of an image which simulates the eye movement of human being. Experimental results of infrared images with different types of backgrounds demonstrate the high efficiency and accuracy of the proposed method to detect and track the dim and small targets.

  5. Production of Y-86 and other radiometals for research purposes using a solution target system.

    PubMed

    Oehlke, Elisabeth; Hoehr, Cornelia; Hou, Xinchi; Hanemaayer, Victoire; Zeisler, Stefan; Adam, Michael J; Ruth, Thomas J; Celler, Anna; Buckley, Ken; Benard, Francois; Schaffer, Paul

    2015-11-01

    Diagnostic radiometals are typically obtained from cyclotrons by irradiating solid targets or from radioisotope generators. These methods have the advantage of high production yields, but require additional solid target handling infrastructure that is not readily available to many cyclotron facilities. Herein, we provide an overview of our results regarding the production of various positron-emitting radiometals using a liquid target system installed on a 13 MeV cyclotron at TRIUMF. Details about the production, purification and quality control of (89)Zr, (68)Ga and for the first time (86)Y are discussed. Aqueous solutions containing 1.35-1.65 g/mL of natural-abundance zinc nitrate, yttrium nitrate, and strontium nitrate were irradiated on a 13 MeV cyclotron using a standard liquid target. Different target body and foil materials were investigated for corrosion. Production yields were calculated using theoretical cross-sections from the EMPIRE code and compared with experimental results. The radioisotopes were extracted from irradiated target material using solid phase extraction methods adapted from previously reported methods, and used for radiolabelling experiments. We demonstrated production quantities that are sufficient for chemical and biological studies for three separate radiometals, (89)Zr (Asat = 360 MBq/μA and yield = 3.17 MBq/μA), (86)Y (Asat = 31 MBq/μA and yield = 1.44 MBq/μA), and (68)Ga (Asat = 141 MBq/μA and yield = 64 MBq/μA) from one hour long irradiations on a typical medical cyclotron. (68)Ga yields were sufficient for potential clinical applications. In order to avoid corrosion of the target body and target foil, nitrate solutions were chosen as well as niobium as target-body material. An automatic loading system enabled up to three production runs per day. The separation efficiency ranged from 82 to 99%. Subsequently, (68)Ga and (86)Y were successfully used to radiolabel DOTA-based chelators while deferoxamine was used to coordinate

  6. Pulsed Magnetic Field System for Magnetized Target Experiments at the National Ignition Facility

    NASA Astrophysics Data System (ADS)

    Rhodes, M. A.; Solberg, J. M.; Logan, B. G.; Perkins, L. J.

    2014-10-01

    High-magnitude magnetic fields applied to inertially confined targets may improve fusion yield and enable basic science applications. We discuss the development of a pulsed magnetic field system for NIF with the goal of applying 10--70 T to various NIF targets. While the driver may be little more than a spark-gap switched capacitor, numerous complex challenges exist in fielding such a system on NIF. The coil surrounding the metallic hohlraum drives induced current in the hohlraum wall. Both the coil and hohlraum wall must survive ohmic heating and J × B forces for several microseconds. Pulsed power must couple to the coil in the NIF environment. The system must not cause late-time optics damage due to debris. There is very limited volume for the driver in a NIF Diagnostic Instrument Manipulator (DIM). We are modeling the coil and hohlraum MHD effects with the LLNL code, ALE3D. However, the simulations lack complete and accurate data for all the required thermo-physical material properties over the expected range of temperatures (below vaporization) and pressures. Therefore, substantial experimental development is planned in the coming year. We present coil and hohlraum simulations results, overall system design, and progress towards an operational prototype test-stand. LLNL is operated by LLNS, LLC, for the U.S. D.O.E., NNSA under Contract DE-AC52-07NA27344. This work was supported by LLNL LDRD 14-ER-028.

  7. An Agrobacterium-delivered CRISPR/Cas9 system for high-frequency targeted mutagenesis in maize.

    PubMed

    Char, Si Nian; Neelakandan, Anjanasree K; Nahampun, Hartinio; Frame, Bronwyn; Main, Marcy; Spalding, Martin H; Becraft, Philip W; Meyers, Blake C; Walbot, Virginia; Wang, Kan; Yang, Bing

    2017-02-01

    CRISPR/Cas9 is a powerful genome editing tool in many organisms, including a number of monocots and dicots. Although the design and application of CRISPR/Cas9 is simpler compared to other nuclease-based genome editing tools, optimization requires the consideration of the DNA delivery and tissue regeneration methods for a particular species to achieve accuracy and efficiency. Here, we describe a public sector system, ISU Maize CRISPR, utilizing Agrobacterium-delivered CRISPR/Cas9 for high-frequency targeted mutagenesis in maize. This system consists of an Escherichia coli cloning vector and an Agrobacterium binary vector. It can be used to clone up to four guide RNAs for single or multiplex gene targeting. We evaluated this system for its mutagenesis frequency and heritability using four maize genes in two duplicated pairs: Argonaute 18 (ZmAgo18a and ZmAgo18b) and dihydroflavonol 4-reductase or anthocyaninless genes (a1 and a4). T 0 transgenic events carrying mono- or diallelic mutations of one locus and various combinations of allelic mutations of two loci occurred at rates over 70% mutants per transgenic events in both Hi-II and B104 genotypes. Through genetic segregation, null segregants carrying only the desired mutant alleles without the CRISPR transgene could be generated in T 1 progeny. Inheritance of an active CRISPR/Cas9 transgene leads to additional target-specific mutations in subsequent generations. Duplex infection of immature embryos by mixing two individual Agrobacterium strains harbouring different Cas9/gRNA modules can be performed for improved cost efficiency. Together, the findings demonstrate that the ISU Maize CRISPR platform is an effective and robust tool to targeted mutagenesis in maize. © 2016 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The Association of Applied Biologists and John Wiley & Sons Ltd.

  8. Finding a Target with an Accessible Global Positioning System

    ERIC Educational Resources Information Center

    Ponchillia, Paul E.; MacKenzie, Nancy; Long, Richard G.; Denton-Smith, Pamela; Hicks, Thomas L.; Miley, Priscilla

    2007-01-01

    This article presents two target-location experiments. In the first experiment, 19 participants located a 25-foot chalk circle 93% of the time with a Global Positioning System (GPS) compared to 12% of the time without it. In a single-subject follow-up experiment, the participant came within 1 foot of the target on all GPS trials. Target-location…

  9. Advances in Orion's On-Orbit Guidance and Targeting System Architecture

    NASA Technical Reports Server (NTRS)

    Scarritt, Sara K.; Fill, Thomas; Robinson, Shane

    2015-01-01

    NASA's manned spaceflight programs have a rich history of advancing onboard guidance and targeting technology. In order to support future missions, the guidance and targeting architecture for the Orion Multi-Purpose Crew Vehicle must be able to operate in complete autonomy, without any support from the ground. Orion's guidance and targeting system must be sufficiently flexible to easily adapt to a wide array of undecided future missions, yet also not cause an undue computational burden on the flight computer. This presents a unique design challenge from the perspective of both algorithm development and system architecture construction. The present work shows how Orion's guidance and targeting system addresses these challenges. On the algorithm side, the system advances the state-of-the-art by: (1) steering burns with a simple closed-loop guidance strategy based on Shuttle heritage, and (2) planning maneuvers with a cutting-edge two-level targeting routine. These algorithms are then placed into an architecture designed to leverage the advantages of each and ensure that they function in concert with one another. The resulting system is characterized by modularity and simplicity. As such, it is adaptable to the on-orbit phases of any future mission that Orion may attempt.

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

    PubMed

    Tan, Hepan; Ge, Xiaoxia; Xie, Lei

    2013-08-01

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

  11. A Fast MEANSHIFT Algorithm-Based Target Tracking System

    PubMed Central

    Sun, Jian

    2012-01-01

    Tracking moving targets in complex scenes using an active video camera is a challenging task. Tracking accuracy and efficiency are two key yet generally incompatible aspects of a Target Tracking System (TTS). A compromise scheme will be studied in this paper. A fast mean-shift-based Target Tracking scheme is designed and realized, which is robust to partial occlusion and changes in object appearance. The physical simulation shows that the image signal processing speed is >50 frame/s. PMID:22969397

  12. Constraints in distortion-invariant target recognition system simulation

    NASA Astrophysics Data System (ADS)

    Iftekharuddin, Khan M.; Razzaque, Md A.

    2000-11-01

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

  13. Engineering of the Magnetized Target Fusion Propulsion System

    NASA Technical Reports Server (NTRS)

    Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Fincher, S.; Polsgrove, T.; Chapman, J.; Philips, A.

    2002-01-01

    Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Structural, thermal and radiation-management design details are presented. Propellant storage and supply options are also discussed and a propulsion system mass estimate is given.

  14. Enhanced laser proton acceleration by target ablation on a femtosecond laser system

    NASA Astrophysics Data System (ADS)

    Liao, Q.; Wu, M. J.; Gong, Z.; Geng, Y. X.; Xu, X. H.; Li, D. Y.; Shou, Y. R.; Zhu, J. G.; Li, C. C.; Yang, M.; Li, T. S.; Lu, H. Y.; Ma, W. J.; Zhao, Y. Y.; Lin, C.; Yan, X. Q.

    2018-06-01

    Proton acceleration during the interaction of an ultraintense (6 × 1019 W/cm2) femtosecond (fs) laser pulse with a thin (2.5 μm) foil target pre-ablated by a picosecond (ps) pulse is experimentally and numerically investigated. Enhancements in both proton cut-off energy and charge are observed with the target ablation due to a large number of energetic electrons generated from the preformed preplasma in front of the target. The enhanced proton beams are successfully collected at 4-9 MeV with ±4% energy spread and then transported to the irradiating platform. The results show that for the interaction between fs laser pulse and μm-thickness target, proton energy and charge can be enhanced by target ablation using a ps laser pulse, which is valuable for application like cancer radiotherapy.

  15. Real-Time Target Motion Animation for Missile Warning System Testing

    DTIC Science & Technology

    2006-04-01

    T. Perkins, R. Sundberg, J. Cordell, Z. Tun , and M. Owen, Real-time Target Motion Animation for Missile Warning System Testing, Proc. SPIE Vol 6208...Z39-18 Real-time target motion animation for missile warning system testing Timothy Perkins*a, Robert Sundberga, John Cordellb, Zaw Tunb, Mark

  16. Landing response of Aedes (Stegomyia) polynesiensis mosquitoes to coloured targets.

    PubMed

    Chambers, E W; Bossin, H C; Ritchie, S A; Russell, R C; Dobson, S L

    2013-09-01

    Aedes polynesiensis Marks (Diptera: Culicidae) is the primary vector of lymphatic filariasis (LF) in the island countries and territories of the South Pacific. In the development of a novel control tool, the response of Ae. polynesiensis to six different colours (three solid fabrics, two patterned fabrics and a plastic tarp) was measured using a digital photographic system. Adult mosquitoes were placed into an environmental chamber and allowed to choose between a white target and one of six experimental targets. Mosquito landing frequency and landing duration were calculated. Adult female Ae. polynesiensis preferred all of the experimental targets to the white control target. Mosquito landing frequency was highest for the solid targets (black, navy blue and red) followed in turn by the two colour pattern targets and the polyethylene target. Mosquito landing duration was greater for experimental targets when compared with white control targets. Mosquito landing frequencies did not change over time during the course of the assay. The response of male Ae. polynesiensis was also measured when exposed to a 100% cotton black target. Male mosquitoes preferred the black target to the white control target, although at levels lower than that observed in female mosquitoes. The results suggest that future investigations evaluating the visual responses of Ae. polynesiensis mosquitoes are warranted, with a special emphasis on semi-field and field-based experiments. © 2013 The Royal Entomological Society.

  17. Solar-Diesel Hybrid Power System Optimization and Experimental Validation

    NASA Astrophysics Data System (ADS)

    Jacobus, Headley Stewart

    As of 2008 1.46 billion people, or 22 percent of the World's population, were without electricity. Many of these people live in remote areas where decentralized generation is the only method of electrification. Most mini-grids are powered by diesel generators, but new hybrid power systems are becoming a reliable method to incorporate renewable energy while also reducing total system cost. This thesis quantifies the measurable Operational Costs for an experimental hybrid power system in Sierra Leone. Two software programs, Hybrid2 and HOMER, are used during the system design and subsequent analysis. Experimental data from the installed system is used to validate the two programs and to quantify the savings created by each component within the hybrid system. This thesis bridges the gap between design optimization studies that frequently lack subsequent validation and experimental hybrid system performance studies.

  18. The polarised internal target for the PAX experiment

    NASA Astrophysics Data System (ADS)

    Ciullo, G.; Barion, L.; Barschel, C.; Grigoriev, K.; Lenisa, P.; Nass, A.; Sarkadi, J.; Statera, M.; Steffens, E.; Tagliente, G.

    2011-05-01

    The PAX (Polarized Antiproton eXperiment) collaboration aims to polarise antiproton beams stored in ring by means of spin-filtering. The experimental setup is based on a polarised internal gas target, surrounded by a detection system for the measurement of spin observables. In this report, we present results from the commission of the PAX target (atomic beam source, openable cell, and polarimeter).

  19. Target detection and localization in shallow water: an experimental demonstration of the acoustic barrier problem at the laboratory scale.

    PubMed

    Marandet, Christian; Roux, Philippe; Nicolas, Barbara; Mars, Jérôme

    2011-01-01

    This study demonstrates experimentally at the laboratory scale the detection and localization of a wavelength-sized target in a shallow ultrasonic waveguide between two source-receiver arrays at 3 MHz. In the framework of the acoustic barrier problem, at the 1/1000 scale, the waveguide represents a 1.1-km-long, 52-m-deep ocean acoustic channel in the kilohertz frequency range. The two coplanar arrays record in the time-domain the transfer matrix of the waveguide between each pair of source-receiver transducers. Invoking the reciprocity principle, a time-domain double-beamforming algorithm is simultaneously performed on the source and receiver arrays. This array processing projects the multireverberated acoustic echoes into an equivalent set of eigenrays, which are defined by their launch and arrival angles. Comparison is made between the intensity of each eigenray without and with a target for detection in the waveguide. Localization is performed through tomography inversion of the acoustic impedance of the target, using all of the eigenrays extracted from double beamforming. The use of the diffraction-based sensitivity kernel for each eigenray provides both the localization and the signature of the target. Experimental results are shown in the presence of surface waves, and methodological issues are discussed for detection and localization.

  20. Opto-mechanical system design of test system for near-infrared and visible target

    NASA Astrophysics Data System (ADS)

    Wang, Chunyan; Zhu, Guodong; Wang, Yuchao

    2014-12-01

    Guidance precision is the key indexes of the guided weapon shooting. The factors of guidance precision including: information processing precision, control system accuracy, laser irradiation accuracy and so on. The laser irradiation precision is an important factor. This paper aimed at the demand of the precision test of laser irradiator,and developed the laser precision test system. The system consists of modified cassegrain system, the wide range CCD camera, tracking turntable and industrial PC, and makes visible light and near infrared target imaging at the same time with a Near IR camera. Through the analysis of the design results, when it exposures the target of 1000 meters that the system measurement precision is43mm, fully meet the needs of the laser precision test.

  1. Limited Efficiency of Drug Delivery to Specific Intracellular Organelles Using Subcellularly "Targeted" Drug Delivery Systems.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2016-01-04

    Many drugs have been designed to act on intracellular targets and to affect intracellular processes inside target cells. For the desired effects to be exerted, these drugs should permeate target cells and reach specific intracellular organelles. This subcellular drug targeting approach has been proposed for enhancement of accumulation of these drugs in target organelles and improved efficiency. This approach is based on drug encapsulation in drug delivery systems (DDSs) and/or their decoration with specific targeting moieties that are intended to enhance the drug/DDS accumulation in the intracellular organelle of interest. During recent years, there has been a constant increase in interest in DDSs targeted to specific intracellular organelles, and many different approaches have been proposed for attaining efficient drug delivery to specific organelles of interest. However, it appears that in many studies insufficient efforts have been devoted to quantitative analysis of the major formulation parameters of the DDSs disposition (efficiency of DDS endocytosis and endosomal escape, intracellular trafficking, and efficiency of DDS delivery to the target organelle) and of the resulting pharmacological effects. Thus, in many cases, claims regarding efficient delivery of drug/DDS to a specific organelle and efficient subcellular targeting appear to be exaggerated. On the basis of the available experimental data, it appears that drugs/DDS decoration with specific targeting residues can affect their intracellular fate and result in preferential drug accumulation within an organelle of interest. However, it is not clear whether these approaches will be efficient in in vivo settings and be translated into preclinical and clinical applications. Studies that quantitatively assess the mechanisms, barriers, and efficiencies of subcellular drug delivery and of the associated toxic effects are required to determine the therapeutic potential of subcellular DDS targeting.

  2. An intelligent re-shieldable targeting system for enhanced tumor accumulation.

    PubMed

    Hu, Zhenpeng; Ma, Jinlong; Fu, Fei; Cui, Chen; Li, Xiaomin; Wang, Xinyu; Wang, Wei; Wan, Yeda; Yuan, Zhi

    2017-12-28

    Programmed ligand targeting strategy promotes the blood circulation stability of nanoparticles by shielding the ligand. However, the irreversible shielding causes the deshielded nanoparticles to be easily recognized and cleared by the reticuloendothelial system (RES), impeding their further retention in the tumor. Here, we for the first time prove the superiority of the intelligent re-shieldable targeting system that is based on the pH-responsive self-assembly/disassembly of gold nanoparticles. The system can enhance the stability of gold nanoparticles in the blood circulation (2.6-fold at 24h), reduce uptake by the RES (35% lower) and improve tumor accumulation (41% higher by analysis of gold content in tumor) effectively compared with the conventional irreversible system. Furthermore, preliminary study indicates that the system could be applied as computed tomography contrast agent in tumor imaging. The in vivo validity of the intelligent re-shieldable targeting system provides inspiration for the design of nanomaterials for cancer diagnosis and treatment. Copyright © 2017. Published by Elsevier B.V.

  3. Conformal piezoelectric systems for clinical and experimental characterization of soft tissue biomechanics

    NASA Astrophysics Data System (ADS)

    Dagdeviren, Canan; Shi, Yan; Joe, Pauline; Ghaffari, Roozbeh; Balooch, Guive; Usgaonkar, Karan; Gur, Onur; Tran, Phat L.; Crosby, Jessi R.; Meyer, Marcin; Su, Yewang; Chad Webb, R.; Tedesco, Andrew S.; Slepian, Marvin J.; Huang, Yonggang; Rogers, John A.

    2015-07-01

    Mechanical assessment of soft biological tissues and organs has broad relevance in clinical diagnosis and treatment of disease. Existing characterization methods are invasive, lack microscale spatial resolution, and are tailored only for specific regions of the body under quasi-static conditions. Here, we develop conformal and piezoelectric devices that enable in vivo measurements of soft tissue viscoelasticity in the near-surface regions of the epidermis. These systems achieve conformal contact with the underlying complex topography and texture of the targeted skin, as well as other organ surfaces, under both quasi-static and dynamic conditions. Experimental and theoretical characterization of the responses of piezoelectric actuator-sensor pairs laminated on a variety of soft biological tissues and organ systems in animal models provide information on the operation of the devices. Studies on human subjects establish the clinical significance of these devices for rapid and non-invasive characterization of skin mechanical properties.

  4. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems

    PubMed Central

    Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Atik Badshah, Shaikh; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2015-01-01

    Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems. PMID:26473828

  5. Progress and Challenges in Developing Aptamer-Functionalized Targeted Drug Delivery Systems.

    PubMed

    Jiang, Feng; Liu, Biao; Lu, Jun; Li, Fangfei; Li, Defang; Liang, Chao; Dang, Lei; Liu, Jin; He, Bing; Badshah, Shaikh Atik; Lu, Cheng; He, Xiaojuan; Guo, Baosheng; Zhang, Xiao-Bing; Tan, Weihong; Lu, Aiping; Zhang, Ge

    2015-10-09

    Aptamers, which can be screened via systematic evolution of ligands by exponential enrichment (SELEX), are superior ligands for molecular recognition due to their high selectivity and affinity. The interest in the use of aptamers as ligands for targeted drug delivery has been increasing due to their unique advantages. Based on their different compositions and preparation methods, aptamer-functionalized targeted drug delivery systems can be divided into two main categories: aptamer-small molecule conjugated systems and aptamer-nanomaterial conjugated systems. In this review, we not only summarize recent progress in aptamer selection and the application of aptamers in these targeted drug delivery systems but also discuss the advantages, challenges and new perspectives associated with these delivery systems.

  6. Achromatic illumination system for small targets

    DOEpatents

    Sigler, Robert D.

    1979-01-01

    A pair of light beams is directed to provide illumination that is substantially uniform from all directions on a small target by a system comprising a pair of corrector windows, a pair of planar reflecting surfaces, a pair of paraboloidal mirrors and a reflecting mirror cavity. The components are arranged so that each of the beams passes through a corrector and is reflected from the planar surface to the paraboloidal mirror, from which it is focused through a hole in the planar surface to the interior of the cavity. The surface of the interior portion of the cavity is shaped to reflect the focused beam three times before the focused reflected beam strikes the target.

  7. Which experimental systems should we use for human microbiome science?

    PubMed

    Douglas, Angela E

    2018-03-01

    Microbiome science is revealing that the phenotype and health of animals, including humans, depend on the sustained function of their resident microorganisms. In this essay, I argue for thoughtful choice of model systems for human microbiome science. A greater variety of experimental systems, including wider use of invertebrate models, would benefit biomedical research, while systems ill-suited to experimental and genetic manipulation can be used to address very limited sets of scientific questions. Microbiome science benefits from the coordinated use of multiple systems, which is facilitated by networks of researchers with expertise in different experimental systems.

  8. Influence of target reflection on three-dimensional range gated reconstruction.

    PubMed

    Chua, Sing Yee; Wang, Xin; Guo, Ningqun; Tan, Ching Seong

    2016-08-20

    The range gated technique is a promising laser ranging method that is widely used in different fields such as surveillance, industry, and military. In a range gated system, a reflected laser pulse returned from the target scene contains key information for range reconstruction, which directly affects the system performance. Therefore, it is necessary to study the characteristics and effects of the target reflection factor. In this paper, theoretical and experimental analyses are performed to investigate the influence of target reflection on three-dimensional (3D) range gated reconstruction. Based on laser detection and ranging (LADAR) and bidirectional reflection distribution function (BRDF) theory, a 3D range gated reconstruction model is derived and the effect on range accuracy is analyzed from the perspectives of target surface reflectivity and angle of laser incidence. Our theoretical and experimental study shows that the range accuracy is proportional to the target surface reflectivity, but it decreases when the angle of incidence increases to adhere to the BRDF model. The presented findings establish a comprehensive understanding of target reflection in 3D range gated reconstruction, which is of interest to various applications such as target recognition and object modeling. This paper provides a reference for future improvement to perform accurate range compensation or correction.

  9. Future System Science Mission Targets for Heliophysics

    NASA Technical Reports Server (NTRS)

    Spann, James; Christensen, Andrew B.; SaintCyr, O. C.; Giles, Barbara I.; Posner, Arik

    2009-01-01

    Heliophysics is a discipline that investigates the science at work from the interface of Earth and space, to the core of the Sun, and to the outer edge of our solar system. This solar-interplanetary-planetary system is vast and inherently coupled on many spatial, temporal and energy scales. The Sun's explosive energy output creates complicated field and plasma structures that when coupled without terrestrial magnetized space, generates an extraordinary complex environment that has practical implications for humanity as we are becoming increasingly dependent on space-based assets. The immense volume of our cosmic neighborhood is the domain of heliophysics. Understanding this domain and the dominant mechanisms that control the transfer of mass and energy requires a system approach that addresses all aspects and regions of the system. The 2009 NASA Heliophysics Roadmap presents a science-focused strategic approach to advance the goal of heliophysics: why does the Sun vary; how do the Earth and heliosphere respond; and what are the impacts on humanity? This talk will present the top 6 prioritized science targets to understand the coupled heliophysics system as presented in the 2009 NASA Heliophysics Roadmap. An exposition of each science target and how it addresses outstanding questions in heliophysics will be discussed.

  10. Engineering of the Magnetized Target Fusion Propulsion System

    NASA Technical Reports Server (NTRS)

    Statham, G.; White, S.; Adams, R. B.; Thio, Y. C. F.; Santarius, J.; Alexander, R.; Chapman, J.; Fincher, S.; Philips, A.; Polsgrove, T.

    2003-01-01

    Engineering details are presented for a magnetized target fusion (MTF) propulsion system designed to support crewed missions to the outer solar system. Basic operation of an MTF propulsion system is introduced. Structural, thermal, radiation-management and electrical design details are presented. The propellant storage and supply system design is also presented. A propulsion system mass estimate and associated performance figures are given. The advantages of helium-3 as a fusion fuel for an advanced MTF system are discussed.

  11. Infrared small target tracking based on SOPC

    NASA Astrophysics Data System (ADS)

    Hu, Taotao; Fan, Xiang; Zhang, Yu-Jin; Cheng, Zheng-dong; Zhu, Bin

    2011-01-01

    The paper presents a low cost FPGA based solution for a real-time infrared small target tracking system. A specialized architecture is presented based on a soft RISC processor capable of running kernel based mean shift tracking algorithm. Mean shift tracking algorithm is realized in NIOS II soft-core with SOPC (System on a Programmable Chip) technology. Though mean shift algorithm is widely used for target tracking, the original mean shift algorithm can not be directly used for infrared small target tracking. As infrared small target only has intensity information, so an improved mean shift algorithm is presented in this paper. How to describe target will determine whether target can be tracked by mean shift algorithm. Because color target can be tracked well by mean shift algorithm, imitating color image expression, spatial component and temporal component are advanced to describe target, which forms pseudo-color image. In order to improve the processing speed parallel technology and pipeline technology are taken. Two RAM are taken to stored images separately by ping-pong technology. A FLASH is used to store mass temp data. The experimental results show that infrared small target is tracked stably in complicated background.

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

    NASA Astrophysics Data System (ADS)

    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.

  13. Targeted systemic gene therapy and molecular imaging of cancer contribution of the vascular-targeted AAVP vector.

    PubMed

    Hajitou, Amin

    2010-01-01

    Gene therapy and molecular-genetic imaging have faced a major problem: the lack of an efficient systemic gene delivery vector. Unquestionably, eukaryotic viruses have been the vectors of choice for gene delivery to mammalian cells; however, they have had limited success in systemic gene therapy. This is mainly due to undesired uptake by the liver and reticuloendothelial system, broad tropism for mammalian cells causing toxicity, and their immunogenicity. On the other hand, prokaryotic viruses such as bacteriophage (phage) have no tropism for mammalian cells, but can be engineered to deliver genes to these cells. However, phage-based vectors have inherently been considered poor vectors for mammalian cells. We have reported a new generation of vascular-targeted systemic hybrid prokaryotic-eukaryotic vectors as chimeras between an adeno-associated virus (AAV) and targeted bacteriophage (termed AAV/phage; AAVP). In this hybrid vector, the targeted bacteriophage serves as a shuttle to deliver the AAV transgene cassette inserted in an intergenomic region of the phage DNA genome. As a proof of concept, we assessed the in vivo efficacy of vector in animal models of cancer by displaying on the phage capsid the cyclic Arg-Gly-Asp (RGD-4C) ligand that binds to alphav integrin receptors specifically expressed on the angiogenic blood vessels of tumors. The ligand-directed vector was able to specifically deliver imaging and therapeutic transgenes to tumors in mice, rats, and dogs while sparing the normal organs. This chapter reviews some gene transfer strategies and the potential of the vascular-targeted AAVP vector for enhancing the effectiveness of existing systemic gene delivery and genetic-imaging technologies. Copyright (c) 2010 Elsevier Inc. All rights reserved.

  14. Endocannabinoid system: potential novel targets for treatment of schizophrenia.

    PubMed

    Saito, Atsushi; Ballinger, Michael D L; Pletnikov, Mikhail V; Wong, Dean F; Kamiya, Atsushi

    2013-05-01

    Accumulating epidemiological evidences suggest that cannabis use during adolescence is a potential environmental risk for the development of psychosis, including schizophrenia. Consistently, clinical and preclinical studies, using pharmacological approaches and genetically engineered animals to target endocannabinoid signaling, reveal the multiple varieties of endocannabinoid system-mediated human and animal behaviors, including cognition and emotion. Recently, there has been substantial progress in understanding the molecular mechanisms of the endocannabinoid system for synaptic communications in the central nervous system. Furthermore, the impact of endocannabinoid signaling on diverse cellular processes during brain development has emerged. Thus, although schizophrenia has etiological complexities, including genetic heterogeneities and multiple environmental factors, it now becomes crucial to explore molecular pathways of convergence of genetic risk factors and endocannabinoid signaling, which may provide us with clues to find novel targets for therapeutic intervention. In this review, epidemiological, clinical, and pathological evidences on the role of the endocannabinoid system in the pathophysiologies of schizophrenia will be presented. We will also make a brief overview of the recent progress in understanding molecular mechanisms of the endocannabinoid system for brain development and function, with particular focus on cannabinoid receptor type 1 (CB1R)-mediated cascade, the most well-characterized cannabinoid receptor. Lastly, we will discuss the potential of the endocannabinoid system in finding novel therapeutic targets for prevention and treatment of schizophrenia. Copyright © 2012 Elsevier Inc. All rights reserved.

  15. Emerging drugs which target the renin-angiotensin-aldosterone system.

    PubMed

    Steckelings, Ulrike Muscha; Paulis, Ludovit; Unger, Thomas; Bader, Michael

    2011-12-01

    The renin-angiotensin-aldosterone system (RAAS) is already the most important target for drugs in the cardiovascular system. However, still new developments are underway to interfere with the system on different levels. The novel strategies to interfere with RAAS aim to reduce the synthesis of the two major RAAS effector hormones, angiotensin (Ang) II and aldosterone, or interfere with their receptors, AT1 and mineralocorticoid receptor, respectively. Moreover, novel targets have been identified in RAAS, such as the (pro)renin receptor, and molecules, which counteract the classical actions of Ang II and are therefore beneficial in cardiovascular diseases. These include the AT2 receptor and the ACE2/Ang-(1-7)/Mas axis. The search for drugs activating these tissue-protective arms of RAAS is therefore the most innovative field in RAAS pharmacology. Most of the novel pharmacological strategies to inhibit the classical RAAS need to prove their superiority above the existing treatment in clinical trials and then have to compete against these now quite cheap drugs in a competitive market. The newly discovered targets have functions beyond the cardiovascular system opening up novel therapeutic areas for drugs interfering with RAAS components.

  16. An Experimental Study of the Correlates and Consequences of Perceiving Oneself to Be the Target of Gender Discrimination

    ERIC Educational Resources Information Center

    Brown, Christia Spears; Bigler, Rebecca S.; Chu, Hui

    2010-01-01

    An experimental methodology was used to test hypotheses concerning the effects of contextual, cognitive-developmental, and individual difference factors on children's views of whether they have been the target of gender discrimination and the possible consequent effect of such views on two forms of state self-esteem: performance and social…

  17. Multiple operating system rotation environment moving target defense

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

    Evans, Nathaniel; Thompson, Michael

    Systems and methods for providing a multiple operating system rotation environment ("MORE") moving target defense ("MTD") computing system are described. The MORE-MTD system provides enhanced computer system security through a rotation of multiple operating systems. The MORE-MTD system increases attacker uncertainty, increases the cost of attacking the system, reduces the likelihood of an attacker locating a vulnerability, and reduces the exposure time of any located vulnerability. The MORE-MTD environment is effectuated by rotation of the operating systems at a given interval. The rotating operating systems create a consistently changing attack surface for remote attackers.

  18. System transfer modelling for automatic target recognizer evaluations

    NASA Astrophysics Data System (ADS)

    Clark, Lloyd G.

    1991-11-01

    Image processing to accomplish automatic recognition of military vehicles has promised increased weapons systems effectiveness and reduced timelines for a number of Department of Defense missions. Automatic Target Recognizers (ATR) are often claimed to be able to recognize many different ground vehicles as possible targets in military air-to- surface targeting applications. The targeting scenario conditions include different vehicle poses and histories as well as a variety of imaging geometries, intervening atmospheres, and background environments. Testing these ATR subsystems in most cases has been limited to a handful of the scenario conditions of interest, as is represented by imagery collected with the desired imaging sensor. The question naturally arises as to how robust the performance of the ATR is for all scenario conditions of interest, not just for the set of imagery upon which an algorithm was trained.

  19. Experiments and synthesis of bone-targeting epirubicin with the water-soluble macromolecular drug delivery systems of oxidized-dextran.

    PubMed

    Yu, Li; Cai, Lin; Hu, Hao; Zhang, Yi

    2014-05-01

    Epirubicin (EPI) is a broad spectrum antineoplastic drug, commonly used as a chemotherapy method to treat osteosarcoma. However, its application has been limited by many side-effects. Therefore, targeted drug delivery to bone has been the aim of current anti-bone-tumor drug studies. Due to the exceptional affinity of Bisphosphonates (BP) to bone, 1-amino-ethylene-1, 1-dephosphate acid (AEDP) was chosen as the bone targeting moiety for water-soluble macromolecular drug delivery systems of oxidized-dextran (OXD) to transport EPI to bone in this article. The bone targeting drug of AEDP-OXD-EPI was designed for the treatment of malignant bone tumors. The successful conjugation of AEDP-OXD-EPI was confirmed by analysis of FTIR and (1)H-NMR spectra. To study the bone-seeking potential of AEDP-OXD-EPI, an in vitro hydroxyapatite (HAp) binding assay and an in vivo experiment of bone-targeting capacity were established. The effectiveness of AEDP-OXD-EPI was demonstrated by inducing apoptosis and necrosis of MG-63 tumor cell line. The obtained experimental data indicated that AEDP-OXD-EPI is an ideal bone-targeting anti-tumor drug.

  20. A Secure and Privacy-Preserving Targeted Ad-System

    NASA Astrophysics Data System (ADS)

    Androulaki, Elli; Bellovin, Steven M.

    Thanks to its low product-promotion cost and its efficiency, targeted online advertising has become very popular. Unfortunately, being profile-based, online advertising methods violate consumers' privacy, which has engendered resistance to the ads. However, protecting privacy through anonymity seems to encourage click-fraud. In this paper, we define consumer's privacy and present a privacy-preserving, targeted ad system (PPOAd) which is resistant towards click fraud. Our scheme is structured to provide financial incentives to all entities involved.

  1. Shilling Attacks Detection in Recommender Systems Based on Target Item Analysis

    PubMed Central

    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

  2. Remote liquid target loading system for LANL two-stage gas gun

    NASA Astrophysics Data System (ADS)

    Gibson, L. L.; Bartram, B.; Dattelbaum, D. M.; Sheffield, S. A.; Stahl, D. B.

    2009-06-01

    A Remote Liquid Loading System (RLLS) was designed to load high hazard liquid materials into targets for gas-gun driven impact experiments. These high hazard liquids tend to react with confining materials in a short period of time, degrading target assemblies and potentially building up pressure through the evolution of gas in the reactions. Therefore, the ability to load a gas gun target in place immediately prior to firing the gun, provides the most stable and reliable target fielding approach. We present the design and evaluation of a RLLS built for the LANL two-stage gas gun. Targets for the gun are made of PMMA and assembled to form a liquid containment cell with a volume of approximately 25 cc. The compatibility of materials was a major consideration in the design of the system, particularly for its use with highly concentrated hydrogen peroxide. Teflon and 304-stainless steel were the two most compatible materials with the materials to be tested. Teflon valves and tubing, as well as stainless steel tubing, were used to handle the liquid, along with a stainless steel reservoir. Preliminary testing was done to ensure proper flow rate and safety. The system has been used to successfully load 97.5 percent hydrogen peroxide into a target cell just prior to a successful multiple magnetic gauge experiment. TV cameras on the target verified the bubble-free filling operation.

  3. Fe3O4 Nanoparticles in Targeted Drug/Gene Delivery Systems

    PubMed Central

    Shen, Lazhen; Li, Bei; Qiao, Yongsheng

    2018-01-01

    Fe3O4 nanoparticles (NPs), the most traditional magnetic nanoparticles, have received a great deal of attention in the biomedical field, especially for targeted drug/gene delivery systems, due to their outstanding magnetism, biocompatibility, lower toxicity, biodegradability, and other features. Naked Fe3O4 NPs are easy to aggregate and oxidize, and thus are often made with various coatings to realize superior properties for targeted drug/gene delivery. In this review, we first list the three commonly utilized synthesis methods of Fe3O4 NPs, and their advantages and disadvantages. In the second part, we describe coating materials that exhibit noticeable features that allow functionalization of Fe3O4 NPs and summarize their methods of drug targeting/gene delivery. Then our efforts will be devoted to the research status and progress of several different functionalized Fe3O4 NP delivery systems loaded with chemotherapeutic agents, and we present targeted gene transitive carriers in detail. In the following section, we illuminate the most effective treatment systems of the combined drug and gene therapy. Finally, we propose opportunities and challenges of the clinical transformation of Fe3O4 NPs targeting drug/gene delivery systems. PMID:29473914

  4. Targeting BRCAness in Gastric Cancer

    DTIC Science & Technology

    2017-10-01

    generated a modified CRISPR system using dCas9-KRAB expressing variants of these cells, and validated them for CRISPRi screening. These reagents will...adenocarcinoma - - - Figure 2. Validation of CRISPR activity following transduction with sgRNAs targeting CD55 and FACS staining with the anti...execution, and interpretation of CRISPR experiments Morgan Diolaiti Specialist UCSF PH.D. Experimental planning and reporting Jefferson Woods SRA

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

    PubMed

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

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

  6. Polarization effects on hard target calibration of lidar systems

    NASA Technical Reports Server (NTRS)

    Kavaya, Michael J.

    1987-01-01

    The theory of hard target calibration of lidar backscatter data, including laboratory measurements of the pertinent target reflectance parameters, is extended to include the effects of polarization of the transmitted and received laser radiation. The bidirectional reflectance-distribution function model of reflectance is expanded to a 4 x 4 matrix allowing Mueller matrix and Stokes vector calculus to be employed. Target reflectance parameters for calibration of lidar backscatter data are derived for various lidar system polarization configurations from integrating sphere and monostatic reflectometer measurements. It is found that correct modeling of polarization effects is mandatory for accurate calibration of hard target reflectance parameters and, therefore, for accurate calibration of lidar backscatter data.

  7. Resolution verification targets for airborne and spaceborne imaging systems at the Stennis Space Center

    NASA Astrophysics Data System (ADS)

    McKellip, Rodney; Yuan, Ding; Graham, William; Holland, Donald E.; Stone, David; Walser, William E.; Mao, Chengye

    1997-06-01

    The number of available spaceborne and airborne systems will dramatically increase over the next few years. A common systematic approach toward verification of these systems will become important for comparing the systems' operational performance. The Commercial Remote Sensing Program at the John C. Stennis Space Center (SSC) in Mississippi has developed design requirements for a remote sensing verification target range to provide a means to evaluate spatial, spectral, and radiometric performance of optical digital remote sensing systems. The verification target range consists of spatial, spectral, and radiometric targets painted on a 150- by 150-meter concrete pad located at SSC. The design criteria for this target range are based upon work over a smaller, prototypical target range at SSC during 1996. This paper outlines the purpose and design of the verification target range based upon an understanding of the systems to be evaluated as well as data analysis results from the prototypical target range.

  8. Ion implantation system and process for ultrasensitive determination of target isotopes

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

    Farmer, III, Orville T.; Liezers, Martin

    2016-09-13

    A system and process are disclosed for ultrasensitive determination of target isotopes of analytical interest in a sample. Target isotopes may be implanted in an implant area on a high-purity substrate to pre-concentrate the target isotopes free of contaminants. A known quantity of a tracer isotope may also be implanted. Target isotopes and tracer isotopes may be determined in a mass spectrometer. The present invention provides ultrasensitive determination of target isotopes in the sample.

  9. Target-Tracking Camera for a Metrology System

    NASA Technical Reports Server (NTRS)

    Liebe, Carl; Bartman, Randall; Chapsky, Jacob; Abramovici, Alexander; Brown, David

    2009-01-01

    An analog electronic camera that is part of a metrology system measures the varying direction to a light-emitting diode that serves as a bright point target. In the original application for which the camera was developed, the metrological system is used to determine the varying relative positions of radiating elements of an airborne synthetic aperture-radar (SAR) antenna as the airplane flexes during flight; precise knowledge of the relative positions as a function of time is needed for processing SAR readings. It has been common metrology system practice to measure the varying direction to a bright target by use of an electronic camera of the charge-coupled-device or active-pixel-sensor type. A major disadvantage of this practice arises from the necessity of reading out and digitizing the outputs from a large number of pixels and processing the resulting digital values in a computer to determine the centroid of a target: Because of the time taken by the readout, digitization, and computation, the update rate is limited to tens of hertz. In contrast, the analog nature of the present camera makes it possible to achieve an update rate of hundreds of hertz, and no computer is needed to determine the centroid. The camera is based on a position-sensitive detector (PSD), which is a rectangular photodiode with output contacts at opposite ends. PSDs are usually used in triangulation for measuring small distances. PSDs are manufactured in both one- and two-dimensional versions. Because it is very difficult to calibrate two-dimensional PSDs accurately, the focal-plane sensors used in this camera are two orthogonally mounted one-dimensional PSDs.

  10. Activity of Nanobins Targeted to the Urokinase Plasminogen Activator System

    NASA Astrophysics Data System (ADS)

    Hankins, Patrick Leon

    While innovations in nanotechnology have resulted in numerous medical advancements for the treatment of cancer, there remains an urgent unmet need for safe and efficient molecular platforms that facilitate the delivery of potent therapeutics to solid tumors. Nanoscale formulations help to overcome the poor bioavailability and systemic organ toxicity associated with many small molecule drugs. Of these nanoparticle drug delivery systems, the greatest clinical successes to date have employed simple nanoscale lipid bilayer assemblies which encase large payloads of chemotherapeutic. While the nanobin platform we have developed has seen initial success through the passive accumulation into tumors, actively targeting nanobins to tumor specific antigens has the potential to increase the therapeutic index of these nanoparticle drugs. We have identified the urokinase plasminogen activator (uPA) and its cell surface bound receptor (uPAR) as ideal targets for drug delivery due to their selective overexpression in metastatic cancers and their important role in tumor progression. From a panel of monoclonal antibodies targeted to uPA and uPAR, we have selected ATN291 and ATN658 as lead candidates for nanobin targeting based on their tumor cell binding and ability to be internalized by cells. A novel method of conjugating antibodies to liposomes was developed for our nanobin platform that preserves the high binding affinity and specificity of these antibodies. We evaluated these uPA- and uPAR-targeted nanobins in several xenograft tumor models and found that they were well-tolerated over a wide range of doses and demonstrated significantly increased antitumor efficacy over untargeted nanobins in multiple tumor types. Preliminary studies suggest that uPA-targeted nanobins are readily internalized by tumor cells, and we believe this is the mechanism for their increased antitumor effect. A method for radiolabeling nanobins with gallium-67 was developed, and preliminary SPECT

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

    PubMed

    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.

  12. Targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system.

    PubMed

    Liang, Zhen; Zhang, Kang; Chen, Kunling; Gao, Caixia

    2014-02-20

    Transcription activator-like effector nucleases (TALENs) and clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated (Cas) systems have emerged as powerful tools for genome editing in a variety of species. Here, we report, for the first time, targeted mutagenesis in Zea mays using TALENs and the CRISPR/Cas system. We designed five TALENs targeting 4 genes, namely ZmPDS, ZmIPK1A, ZmIPK, ZmMRP4, and obtained targeting efficiencies of up to 23.1% in protoplasts, and about 13.3% to 39.1% of the transgenic plants were somatic mutations. Also, we constructed two gRNAs targeting the ZmIPK gene in maize protoplasts, at frequencies of 16.4% and 19.1%, respectively. In addition, the CRISPR/Cas system induced targeted mutations in Z. mays protoplasts with efficiencies (13.1%) similar to those obtained with TALENs (9.1%). Our results show that both TALENs and the CRISPR/Cas system can be used for genome modification in maize. Copyright © 2013. Published by Elsevier Ltd.

  13. Mitochondrion: A Promising Target for Nanoparticle-Based Vaccine Delivery Systems

    PubMed Central

    Wen, Ru; Umeano, Afoma C.; Francis, Lily; Sharma, Nivita; Tundup, Smanla; Dhar, Shanta

    2016-01-01

    Vaccination is one of the most popular technologies in disease prevention and eradication. It is promising to improve immunization efficiency by using vectors and/or adjuvant delivery systems. Nanoparticle (NP)-based delivery systems have attracted increasing interest due to enhancement of antigen uptake via prevention of vaccine degradation in the biological environment and the intrinsic immune-stimulatory properties of the materials. Mitochondria play paramount roles in cell life and death and are promising targets for vaccine delivery systems to effectively induce immune responses. In this review, we focus on NPs-based delivery systems with surfaces that can be manipulated by using mitochondria targeting moieties for intervention in health and disease. PMID:27258316

  14. Literature-based condition-specific miRNA-mRNA target prediction.

    PubMed

    Oh, Minsik; Rhee, Sungmin; Moon, Ji Hwan; Chae, Heejoon; Lee, Sunwon; Kang, Jaewoo; Kim, Sun

    2017-01-01

    miRNAs are small non-coding RNAs that regulate gene expression by binding to the 3'-UTR of genes. Many recent studies have reported that miRNAs play important biological roles by regulating specific mRNAs or genes. Many sequence-based target prediction algorithms have been developed to predict miRNA targets. However, these methods are not designed for condition-specific target predictions and produce many false positives; thus, expression-based target prediction algorithms have been developed for condition-specific target predictions. A typical strategy to utilize expression data is to leverage the negative control roles of miRNAs on genes. To control false positives, a stringent cutoff value is typically set, but in this case, these methods tend to reject many true target relationships, i.e., false negatives. To overcome these limitations, additional information should be utilized. The literature is probably the best resource that we can utilize. Recent literature mining systems compile millions of articles with experiments designed for specific biological questions, and the systems provide a function to search for specific information. To utilize the literature information, we used a literature mining system, BEST, that automatically extracts information from the literature in PubMed and that allows the user to perform searches of the literature with any English words. By integrating omics data analysis methods and BEST, we developed Context-MMIA, a miRNA-mRNA target prediction method that combines expression data analysis results and the literature information extracted based on the user-specified context. In the pathway enrichment analysis using genes included in the top 200 miRNA-targets, Context-MMIA outperformed the four existing target prediction methods that we tested. In another test on whether prediction methods can re-produce experimentally validated target relationships, Context-MMIA outperformed the four existing target prediction methods. In summary

  15. Development of experimental systems for material sciences under microgravity

    NASA Technical Reports Server (NTRS)

    Tanii, Jun; Obi, Shinzo; Kamimiyata, Yotsuo; Ajimine, Akio

    1988-01-01

    As part of the Space Experiment Program of the Society of Japanese Aerospace Companies, three experimental systems (G452, G453, G454) have been developed for materials science studies under microgravity by the NEC Corporation. These systems are to be flown as Get Away Special payloads for studying the feasibility of producing new materials. Together with the experimental modules carrying the hardware specific to the experiment, the three systems all comprise standard subsystems consisting of a power supply, sequence controller, temperature controller, data recorder, and video recorder.

  16. Differences in cytokinin control on cellular dynamics of zucchini cotyledons cultivated in two experimental systems.

    PubMed

    Stoynova-Bakalova, E; Petrov, P; Gigova, L; Ivanova, N

    2011-01-01

    The effect of endogenous cytokinins on the pattern of palisade cell division post-germination does not depend on the conditions of cotyledon development -in planta (attached to seedlings) or in vitro (isolated from dry zucchini seeds and cultured on water). In cotyledons originating from 4-day-old seedlings (experimental system 1), exogenous cytokinin temporarily (in the first 2 day of cultivation) enhanced post-mitotic cell enlargement of palisade cells, mainly due to enhanced water uptake and use of cell storage compounds, all of which lead to cotyledon senescence. Cytokinin is not able to resume the completed palisade cell division on day 5. As a result, the number of cells and the final areas of treated and control cotyledons are quite similar. By contrast, the effects of cytokinin on cotyledons isolated from dry seeds (experimental system 2) are better expressed, promoting an increase in number of palisade cells accompanied by additional cotyledon area enlargement. However, the prolonged post-mitotic cell expansion in control cotyledons compensates for the reduced speed of cell growth and division activity and decreases differences in final cotyledon area between treatments. The results define cell division as the primary target of cytokinin stimulation in cotyledon tissues competent for division, and determine the temporal patterns of palisade cell cycling related to cotyledon age. This knowledge permits a better choice of experimental system to study effects on cell proliferation and cell growth, as well as cell enlargement and senescence-related events using physiologically homogeneous material. © 2010 German Botanical Society and The Royal Botanical Society of the Netherlands.

  17. Functional Requirements of a Target Description System for Vulnerability Analysis

    DTIC Science & Technology

    1979-11-01

    called GIFT .1,2 Together the COMGEOM description model and GIFT codes make up the BRL’s target description system. The significance of a target...and modifying target descriptions are described. 1 Lawrence W. Bain, Jr. and Mathew J. Reisinger, "The GIFT Code User Manual; Volume 1...34The GIFT Code User Manual; Volume II, The Output Options," unpublished draft of BRL report. II. UNDERLYING PHILOSOPHY The BRL has a computer

  18. Multiple targets detection method in detection of UWB through-wall radar

    NASA Astrophysics Data System (ADS)

    Yang, Xiuwei; Yang, Chuanfa; Zhao, Xingwen; Tian, Xianzhong

    2017-11-01

    In this paper, the problems and difficulties encountered in the detection of multiple moving targets by UWB radar are analyzed. The experimental environment and the penetrating radar system are established. An adaptive threshold method based on local area is proposed to effectively filter out clutter interference The objective of the moving target is analyzed, and the false target is further filtered out by extracting the target feature. Based on the correlation between the targets, the target matching algorithm is proposed to improve the detection accuracy. Finally, the effectiveness of the above method is verified by practical experiment.

  19. System considerations for detection and tracking of small targets using passive sensors

    NASA Astrophysics Data System (ADS)

    DeBell, David A.

    1991-08-01

    Passive sensors provide only a few discriminants to assist in threat assessment of small targets. Tracking of the small targets provides additional discriminants. This paper discusses the system considerations for tracking small targets using passive sensors, in particular EO sensors. Tracking helps establish good versus bad detections. Discussed are the requirements to be placed on the sensor system's accuracy, with respect to knowledge of the sightline direction. The detection of weak targets sets a requirement for two levels of tracking in order to reduce processor throughput. A system characteristic is the need to track all detections. For low thresholds, this can mean a heavy track burden. Therefore, thresholds must be adaptive in order not to saturate the processors. Second-level tracks must develop a range estimate in order to assess threat. Sensor platform maneuvers are required if the targets are moving. The need for accurate pointing, good stability, and a good update rate will be shown quantitatively, relating to track accuracy and track association.

  20. Targeting BRCAness in Gastric Cancer

    DTIC Science & Technology

    2017-10-01

    inhibitors. We also generated a modified CRISPR system using dCas9-KRAB expressing variants of these cells, and validated them for CRISPRi screening...Figure 2. Validation of CRISPR activity following transduction with sgRNAs targeting CD55 and FACS staining with the anti-CD55 antibody. Data shown...interpretation of CRISPR experiments Morgan Diolaiti Specialist UCSF PH.D. Experimental planning and reporting Jefferson Woods SRA UCSF B.S. Perform drug

  1. Appraisal of comparative single-case experimental designs for instructional interventions with non-reversible target behaviors: Introducing the CSCEDARS ("Cedars").

    PubMed

    Schlosser, Ralf W; Belfiore, Phillip J; Sigafoos, Jeff; Briesch, Amy M; Wendt, Oliver

    2018-05-28

    Evidence-based practice as a process requires the appraisal of research as a critical step. In the field of developmental disabilities, single-case experimental designs (SCEDs) figure prominently as a means for evaluating the effectiveness of non-reversible instructional interventions. Comparative SCEDs contrast two or more instructional interventions to document their relative effectiveness and efficiency. As such, these designs have great potential to inform evidence-based decision-making. To harness this potential, however, interventionists and authors of systematic reviews need tools to appraise the evidence generated by these designs. Our literature review revealed that existing tools do not adequately address the specific methodological considerations of comparative SCEDs that aim to compare instructional interventions of non-reversible target behaviors. The purpose of this paper is to introduce the Comparative Single-Case Experimental Design Rating System (CSCEDARS, "cedars") as a tool for appraising the internal validity of comparative SCEDs of two or more non-reversible instructional interventions. Pertinent literature will be reviewed to establish the need for this tool and to underpin the rationales for individual rating items. Initial reliability information will be provided as well. Finally, directions for instrument validation will be proposed. Copyright © 2018 Elsevier Ltd. All rights reserved.

  2. Experimental system design for the integration of trapped-ion and superconducting qubit systems

    NASA Astrophysics Data System (ADS)

    De Motte, D.; Grounds, A. R.; Rehák, M.; Rodriguez Blanco, A.; Lekitsch, B.; Giri, G. S.; Neilinger, P.; Oelsner, G.; Il'ichev, E.; Grajcar, M.; Hensinger, W. K.

    2016-12-01

    We present a design for the experimental integration of ion trapping and superconducting qubit systems as a step towards the realization of a quantum hybrid system. The scheme addresses two key difficulties in realizing such a system: a combined microfabricated ion trap and superconducting qubit architecture, and the experimental infrastructure to facilitate both technologies. Developing upon work by Kielpinski et al. (Phys Rev Lett 108(13):130504, 2012. doi: 10.1103/PhysRevLett.108.130504), we describe the design, simulation and fabrication process for a microfabricated ion trap capable of coupling an ion to a superconducting microwave LC circuit with a coupling strength in the tens of kHz. We also describe existing difficulties in combining the experimental infrastructure of an ion trapping set-up into a dilution refrigerator with superconducting qubits and present solutions that can be immediately implemented using current technology.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27690051

  4. A system dynamics optimization framework to achieve population desired of average weight target

    NASA Astrophysics Data System (ADS)

    Abidin, Norhaslinda Zainal; Zulkepli, Jafri Haji; Zaibidi, Nerda Zura

    2017-11-01

    Obesity is becoming a serious problem in Malaysia as it has been rated as the highest among Asian countries. The aim of the paper is to propose a system dynamics (SD) optimization framework to achieve population desired weight target based on the changes in physical activity behavior and its association to weight and obesity. The system dynamics approach of stocks and flows diagram was used to quantitatively model the impact of both behavior on the population's weight and obesity trends. This work seems to bring this idea together and highlighting the interdependence of the various aspects of eating and physical activity behavior on the complex of human weight regulation system. The model was used as an experimentation vehicle to investigate the impacts of changes in physical activity on weight and prevalence of obesity implications. This framework paper provides evidence on the usefulness of SD optimization as a strategic decision making approach to assist in decision making related to obesity prevention. SD applied in this research is relatively new in Malaysia and has a high potential to apply to any feedback models that address the behavior cause to obesity.

  5. Receptor-Mediated Drug Delivery Systems Targeting to Glioma

    PubMed Central

    Wang, Shanshan; Meng, Ying; Li, Chengyi; Qian, Min; Huang, Rongqin

    2015-01-01

    Glioma has been considered to be the most frequent primary tumor within the central nervous system (CNS). The complexity of glioma, especially the existence of the blood-brain barrier (BBB), makes the survival and prognosis of glioma remain poor even after a standard treatment based on surgery, radiotherapy, and chemotherapy. This provides a rationale for the development of some novel therapeutic strategies. Among them, receptor-mediated drug delivery is a specific pattern taking advantage of differential expression of receptors between tumors and normal tissues. The strategy can actively transport drugs, such as small molecular drugs, gene medicines, and therapeutic proteins to glioma while minimizing adverse reactions. This review will summarize recent progress on receptor-mediated drug delivery systems targeting to glioma, and conclude the challenges and prospects of receptor-mediated glioma-targeted therapy for future applications. PMID:28344260

  6. Experimental gingivitis, bacteremia and systemic biomarkers: a randomized clinical trial.

    PubMed

    Kinane, D F; Zhang, P; Benakanakere, M; Singleton, J; Biesbrock, A; Nonnenmacher, C; He, T

    2015-12-01

    Bacteremia and systemic inflammatory markers are associated with periodontal and systemic diseases and may be linking mechanisms between these conditions. We hypothesized that in the development of gingival inflammation, systemic markers of inflammation and bacteremia would increase. To study the effect of bacteremia on systemic inflammatory markers, we recruited 80 subjects to participate in an experimental gingivitis study. Subjects were stratified based on gender, smoking and the number of bleeding sites and then randomized to one of two groups: control group (n = 40) or experimental gingivitis group (n = 40). Subjects in the control group conducted an oral hygiene regimen: brushing twice daily with a regular sodium fluoride cavity protection dentifrice and a standard manual toothbrush, flossing twice daily, and mouth rinsing with an anti-cavity fluoride rinse once daily. The experimental group stopped brushing and flossing, and used only the fluoride anti-cavity mouth rinse for 21 d. Seventy-nine of 80 subjects were evaluable. One subject in the control group was excluded from the results due to antibiotic use during the study. Our data showed the experimental gingivitis group exhibited a significant (p < 0.05) increase in dental plaque level and gingival inflammatory indices relative to baseline and the control group but a decrease in bacteremia and soluble intercellular adhesion molecule-1 levels vs. baseline. Bacteremia was negatively correlated with gingival inflammatory indices and soluble intercellular adhesion molecule-1 levels in the experimental gingivitis group, thus negating our hypothesis. We conclude that there are marked differences in systemic cytokine levels over the course of short-term experimentally induced gingivitis and further conclude that a long-term periodontitis study must be considered to address mechanisms whereby oral diseases may affect systemic diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  7. Laser-driven proton acceleration with nanostructured targets

    NASA Astrophysics Data System (ADS)

    Vallières, Simon; Morabito, Antonia; Veltri, Simona; Scisciò, Massimiliano; Barberio, Marianna; Antici, Patrizio

    2017-05-01

    Laser-driven particle acceleration has become a growing field of research, in particular for its numerous interesting applications. One of the most common proton acceleration mechanism that is obtained on typically available multi-hundred TW laser systems is based on the irradiation of thin solid metal foils by the intense laser, generating the proton acceleration on its rear target surface. The efficiency of this acceleration scheme strongly depends on the type of target used. Improving the acceleration mechanism, i.e. enhancing parameters such as maximum proton energy, laminarity, efficiency, monocromaticy, and number of accelerated particles, is heavily depending on the laser-to-target absorption, where obviously cheap and easy to implement targets are best candidates. In this work, we present nanostructured targets that are able to increase the absorption of light compared to what can be achieved with a classical solid (non-nanostructured) target and are produced with a method that is much simpler and cheaper than conventional lithographic processes. Several layers of gold nanoparticles were deposited on solid targets (aluminum, Mylar and multiwalled carbon nanotube buckypaper) and allow for an increased photon absorption. This ultimately permits to increase the laser-to-particle energy transfer, and thus to enhance the yield in proton production. Experimental characterization results on the nanostructured films are presented (UV-Vis spectroscopy and AFM), along with preliminary experimental proton spectra obtained at the JLF-TITAN laser facility at LLNL.

  8. An experimental study of the reflection from spherical and flat ended cylindrical targets suitable for fetal Doppler performance assessment.

    PubMed

    Preston, R C; Bond, A D

    1997-01-01

    The performance of small-diameter targets suitable for use as oscillating targets for testing the sensitivity of Doppler fetal heartbeat detectors has been systematically studied. Experimental results are presented in the 1.6-3.0 MHz frequency range for the plane-wave reflection loss for a total of 16 targets: spherical balls made of stainless steel; hemispherical-ended rods made of PTFE; and flat-ended rods made of stainless steel, PTFE, polycarbonate, and tungsten carbide. Results show that the fine-structure variation of reflection loss with frequency is greatest in the case of spherical ball targets and least for flat-ended targets. It has been shown that, providing care is taken during manufacture, the reflection loss from a flat-ended target can be predicted using a simple theory based on a plane disc reflector. Tungsten carbide targets consisting of a long rod with a diameter of 1.6 mm tapered down to a cylindrical flat end with a diameter of 0.4, 0.5, and 0.6 mm have been shown to provide reflection losses of between 60 and 40 dB, and to have a smooth variation of reflection loss with frequency. They can also be manufactured in a form that allows no significant interference from the supporting structure and, therefore, are ideal targets to meet the requirements of International Electrotechnical Commission 1266:1995.

  9. Beacon Collision Avoidance System (BCAS) Alternative Concepts for Determining Target Positions

    DOT National Transportation Integrated Search

    1978-09-01

    The (Litchford) Beacon-based Collision Avoidance System concept requires the computation of target range and bearing relative to the BCAS aircraft. Techniques for determining target range and bearing under four different assumptions about the ground ...

  10. Colon-targeted oral drug delivery systems: design trends and approaches.

    PubMed

    Amidon, Seth; Brown, Jack E; Dave, Vivek S

    2015-08-01

    Colon-specific drug delivery systems (CDDS) are desirable for the treatment of a range of local diseases such as ulcerative colitis, Crohn's disease, irritable bowel syndrome, chronic pancreatitis, and colonic cancer. In addition, the colon can be a potential site for the systemic absorption of several drugs to treat non-colonic conditions. Drugs such as proteins and peptides that are known to degrade in the extreme gastric pH, if delivered to the colon intact, can be systemically absorbed by colonic mucosa. In order to achieve effective therapeutic outcomes, it is imperative that the designed delivery system specifically targets the drugs into the colon. Several formulation approaches have been explored in the development colon-targeted drug delivery systems. These approaches involve the use of formulation components that interact with one or more aspects of gastrointestinal (GI) physiology, such as the difference in the pH along the GI tract, the presence of colonic microflora, and enzymes, to achieve colon targeting. This article highlights the factors influencing colon-specific drug delivery and colonic bioavailability, and the limitations associated with CDDS. Further, the review provides a systematic discussion of various conventional, as well as relatively newer formulation approaches/technologies currently being utilized for the development of CDDS.

  11. Systems level mapping of metabolic complexity in Mycobacterium tuberculosis to identify high-value drug targets.

    PubMed

    Vashisht, Rohit; Bhat, Ashwini G; Kushwaha, Shreeram; Bhardwaj, Anshu; Brahmachari, Samir K

    2014-10-11

    The effectiveness of current therapeutic regimens for Mycobacterium tuberculosis (Mtb) is diminished by the need for prolonged therapy and the rise of drug resistant/tolerant strains. This global health threat, despite decades of basic research and a wealth of legacy knowledge, is due to a lack of systems level understanding that can innovate the process of fast acting and high efficacy drug discovery. The enhanced functional annotations of the Mtb genome, which were previously obtained through a crowd sourcing approach was used to reconstruct the metabolic network of Mtb in a bottom up manner. We represent this information by developing a novel Systems Biology Spindle Map of Metabolism (SBSM) and comprehend its static and dynamic structure using various computational approaches based on simulation and design. The reconstructed metabolism of Mtb encompasses 961 metabolites, involved in 1152 reactions catalyzed by 890 protein coding genes, organized into 50 pathways. By accounting for static and dynamic analysis of SBSM in Mtb we identified various critical proteins required for the growth and survival of bacteria. Further, we assessed the potential of these proteins as putative drug targets that are fast acting and less toxic. Further, we formulate a novel concept of metabolic persister genes (MPGs) and compared our predictions with published in vitro and in vivo experimental evidence. Through such analyses, we report for the first time that de novo biosynthesis of NAD may give rise to bacterial persistence in Mtb under conditions of metabolic stress induced by conventional anti-tuberculosis therapy. We propose such MPG's as potential combination of drug targets for existing antibiotics that can improve their efficacy and efficiency for drug tolerant bacteria. The systems level framework formulated by us to identify potential non-toxic drug targets and strategies to circumvent the issue of bacterial persistence can substantially aid in the process of TB drug

  12. Polymeric nanoparticles for targeted drug delivery system for cancer therapy.

    PubMed

    Masood, Farha

    2016-03-01

    A targeted delivery system based on the polymeric nanoparticles as a drug carrier represents a marvelous avenue for cancer therapy. The pivotal characteristics of this system include biodegradability, biocompatibility, non-toxicity, prolonged circulation and a wide payload spectrum of a therapeutic agent. Other outstanding features are their distinctive size and shape properties for tissue penetration via an active and passive targeting, specific cellular/subcellular trafficking pathways and facile control of cargo release by sophisticated material engineering. In this review, the current implications of encapsulation of anticancer agents within polyhydroxyalkanoates, poly-(lactic-co-glycolic acid) and cyclodextrin based nanoparticles to precisely target the tumor site, i.e., cell, tissue and organ are highlighted. Furthermore, the promising perspectives in this emerging field are discussed. Copyright © 2015 Elsevier B.V. All rights reserved.

  13. Systems biology-embedded target validation: improving efficacy in drug discovery.

    PubMed

    Vandamme, Drieke; Minke, Benedikt A; Fitzmaurice, William; Kholodenko, Boris N; Kolch, Walter

    2014-01-01

    The pharmaceutical industry is faced with a range of challenges with the ever-escalating costs of drug development and a drying out of drug pipelines. By harnessing advances in -omics technologies and moving away from the standard, reductionist model of drug discovery, there is significant potential to reduce costs and improve efficacy. Embedding systems biology approaches in drug discovery, which seek to investigate underlying molecular mechanisms of potential drug targets in a network context, will reduce attrition rates by earlier target validation and the introduction of novel targets into the currently stagnant market. Systems biology approaches also have the potential to assist in the design of multidrug treatments and repositioning of existing drugs, while stratifying patients to give a greater personalization of medical treatment. © 2013 Wiley Periodicals, Inc.

  14. Point target detection utilizing super-resolution strategy for infrared scanning oversampling system

    NASA Astrophysics Data System (ADS)

    Wang, Longguang; Lin, Zaiping; Deng, Xinpu; An, Wei

    2017-11-01

    To improve the resolution of remote sensing infrared images, infrared scanning oversampling system is employed with information amount quadrupled, which contributes to the target detection. Generally the image data from double-line detector of infrared scanning oversampling system is shuffled to a whole oversampled image to be post-processed, whereas the aliasing between neighboring pixels leads to image degradation with a great impact on target detection. This paper formulates a point target detection method utilizing super-resolution (SR) strategy concerning infrared scanning oversampling system, with an accelerated SR strategy proposed to realize fast de-aliasing of the oversampled image and an adaptive MRF-based regularization designed to achieve the preserving and aggregation of target energy. Extensive experiments demonstrate the superior detection performance, robustness and efficiency of the proposed method compared with other state-of-the-art approaches.

  15. A far-field radio-frequency experimental exposure system with unrestrained mice.

    PubMed

    Hansen, Jared W; Asif, Sajid; Singelmann, Lauren; Khan, Muhammad Saeed; Ghosh, Sumit; Gustad, Tom; Doetkott, Curt; Braaten, Benjamin D; Ewert, Daniel L

    2015-01-01

    Many studies have been performed on exploring the effects of radio-frequency (RF) energy on biological function in vivo. In particular, gene expression results have been inconclusive due, in part, to a lack of a standardized experimental procedure. This research describes a new far field RF exposure system for unrestrained murine models that reduces experimental error. The experimental procedure includes the materials used, the creation of a patch antenna, the uncertainty analysis of the equipment, characterization of the test room, experimental equipment used and setup, power density and specific absorption rate experiment, and discussion. The result of this research is an experimental exposure system to be applied to future biological studies.

  16. Image-guided ex-vivo targeting accuracy using a laparoscopic tissue localization system

    NASA Astrophysics Data System (ADS)

    Bieszczad, Jerry; Friets, Eric; Knaus, Darin; Rauth, Thomas; Herline, Alan; Miga, Michael; Galloway, Robert; Kynor, David

    2007-03-01

    In image-guided surgery, discrete fiducials are used to determine a spatial registration between the location of surgical tools in the operating theater and the location of targeted subsurface lesions and critical anatomic features depicted in preoperative tomographic image data. However, the lack of readily localized anatomic landmarks has greatly hindered the use of image-guided surgery in minimally invasive abdominal procedures. To address these needs, we have previously described a laser-based system for localization of internal surface anatomy using conventional laparoscopes. During a procedure, this system generates a digitized, three-dimensional representation of visible anatomic surfaces in the abdominal cavity. This paper presents the results of an experiment utilizing an ex-vivo bovine liver to assess subsurface targeting accuracy achieved using our system. During the experiment, several radiopaque targets were inserted into the liver parenchyma. The location of each target was recorded using an optically-tracked insertion probe. The liver surface was digitized using our system, and registered with the liver surface extracted from post-procedure CT images. This surface-based registration was then used to transform the position of the inserted targets into the CT image volume. The target registration error (TRE) achieved using our surface-based registration (given a suitable registration algorithm initialization) was 2.4 mm +/- 1.0 mm. A comparable TRE (2.6 mm +/- 1.7 mm) was obtained using a registration based on traditional fiducial markers placed on the surface of the same liver. These results indicate the potential of fiducial-free, surface-to-surface registration for image-guided lesion targeting in minimally invasive abdominal surgery.

  17. LHRH-Targeted Drug Delivery Systems for Cancer Therapy.

    PubMed

    Li, Xiaoning; Taratula, Oleh; Taratula, Olena; Schumann, Canan; Minko, Tamara

    2017-01-01

    Targeted delivery of therapeutic and diagnostic agents to cancer sites has significant potential to improve the therapeutic outcome of treatment while minimizing severe side effects. It is widely accepted that decoration of the drug delivery systems with targeting ligands that bind specifically to the receptors on the cancer cells is a promising strategy that may substantially enhance accumulation of anticancer agents in the tumors. Due to the transformed cellular nature, cancer cells exhibit a variety of overexpressed cell surface receptors for peptides, hormones, and essential nutrients, providing a significant number of target candidates for selective drug delivery. Among others, luteinizing hormonereleasing hormone (LHRH) receptors are overexpressed in the majority of cancers, while their expression in healthy tissues, apart from pituitary cells, is limited. The recent studies indicate that LHRH peptides can be employed to efficiently guide anticancer and imaging agents directly to cancerous cells, thereby increasing the amount of these substances in tumor tissue and preventing normal cells from unnecessary exposure. This manuscript provides an overview of the targeted drug delivery platforms that take advantage of the LHRH receptors overexpression by cancer cells.

  18. Comparison of LIDAR system performance for alternative single-mode receiver architectures: modeling and experimental validation

    NASA Astrophysics Data System (ADS)

    Toliver, Paul; Ozdur, Ibrahim; Agarwal, Anjali; Woodward, T. K.

    2013-05-01

    In this paper, we describe a detailed performance comparison of alternative single-pixel, single-mode LIDAR architectures including (i) linear-mode APD-based direct-detection, (ii) optically-preamplified PIN receiver, (iii) PINbased coherent-detection, and (iv) Geiger-mode single-photon-APD counting. Such a comparison is useful when considering next-generation LIDAR on a chip, which would allow one to leverage extensive waveguide-based structures and processing elements developed for telecom and apply them to small form-factor sensing applications. Models of four LIDAR transmit and receive systems are described in detail, which include not only the dominant sources of receiver noise commonly assumed in each of the four detection limits, but also additional noise terms present in realistic implementations. These receiver models are validated through the analysis of detection statistics collected from an experimental LIDAR testbed. The receiver is reconfigurable into four modes of operation, while transmit waveforms and channel characteristics are held constant. The use of a diffuse hard target highlights the importance of including speckle noise terms in the overall system analysis. All measurements are done at 1550 nm, which offers multiple system advantages including less stringent eye safety requirements and compatibility with available telecom components, optical amplification, and photonic integration. Ultimately, the experimentally-validated detection statistics can be used as part of an end-to-end system model for projecting rate, range, and resolution performance limits and tradeoffs of alternative integrated LIDAR architectures.

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

    NASA Astrophysics Data System (ADS)

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

    2012-06-01

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

  20. Automated multiple target detection and tracking in UAV videos

    NASA Astrophysics Data System (ADS)

    Mao, Hongwei; Yang, Chenhui; Abousleman, Glen P.; Si, Jennie

    2010-04-01

    In this paper, a novel system is presented to detect and track multiple targets in Unmanned Air Vehicles (UAV) video sequences. Since the output of the system is based on target motion, we first segment foreground moving areas from the background in each video frame using background subtraction. To stabilize the video, a multi-point-descriptor-based image registration method is performed where a projective model is employed to describe the global transformation between frames. For each detected foreground blob, an object model is used to describe its appearance and motion information. Rather than immediately classifying the detected objects as targets, we track them for a certain period of time and only those with qualified motion patterns are labeled as targets. In the subsequent tracking process, a Kalman filter is assigned to each tracked target to dynamically estimate its position in each frame. Blobs detected at a later time are used as observations to update the state of the tracked targets to which they are associated. The proposed overlap-rate-based data association method considers the splitting and merging of the observations, and therefore is able to maintain tracks more consistently. Experimental results demonstrate that the system performs well on real-world UAV video sequences. Moreover, careful consideration given to each component in the system has made the proposed system feasible for real-time applications.

  1. A Retrieval System for Radioactive Target Materials at the NIF

    NASA Astrophysics Data System (ADS)

    Krieger, M.; Shibata, K.; Fallica, J.; Henchen, R.; Pogozelski, E.; Padalino, S.; Sangster, T. C.; Suny Collaboration; Laboratory Collaboration

    2011-10-01

    Currently, solid radioactive material collection from the NIF target chamber is performed via the DIM. The retrieval process takes several hours to complete. To decrease this time for short lived radioisotopes, the Target Materials Retrieval System (TMRS) is being designed to move a radioactive sample from the target chamber to the counting station in less than 50 seconds, using a closed-loop helium filled RaPToRS system. The TMRS consists of three components: the retrieval apparatus, RaPToRS and the counting station. Starting at 0.5 meters from TCC, the sample will move from the vacuum chamber, travel through 60 meters of 10 centimeter diameter RaPToRS tubes, reaching speeds of 10 m/s. The sample will then arrive at the counting station, where it be robotically placed in front of a gamma ray detector. The use of helium will decrease background gamma radiation produced by activated N2 normally found in a pressurized air system. This work was supported in part by the US Department of Energy through the LLE.

  2. Optical cell monitoring system for underwater targets

    NASA Astrophysics Data System (ADS)

    Moon, SangJun; Manzur, Fahim; Manzur, Tariq; Demirci, Utkan

    2008-10-01

    We demonstrate a cell based detection system that could be used for monitoring an underwater target volume and environment using a microfluidic chip and charge-coupled-device (CCD). This technique allows us to capture specific cells and enumerate these cells on a large area on a microchip. The microfluidic chip and a lens-less imaging platform were then merged to monitor cell populations and morphologies as a system that may find use in distributed sensor networks. The chip, featuring surface chemistry and automatic cell imaging, was fabricated from a cover glass slide, double sided adhesive film and a transparent Polymethlymetacrylate (PMMA) slab. The optically clear chip allows detecting cells with a CCD sensor. These chips were fabricated with a laser cutter without the use of photolithography. We utilized CD4+ cells that are captured on the floor of a microfluidic chip due to the ability to address specific target cells using antibody-antigen binding. Captured CD4+ cells were imaged with a fluorescence microscope to verify the chip specificity and efficiency. We achieved 70.2 +/- 6.5% capturing efficiency and 88.8 +/- 5.4% specificity for CD4+ T lymphocytes (n = 9 devices). Bright field images of the captured cells in the 24 mm × 4 mm × 50 μm microfluidic chip were obtained with the CCD sensor in one second. We achieved an inexpensive system that rapidly captures cells and images them using a lens-less CCD system. This microfluidic device can be modified for use in single cell detection utilizing a cheap light-emitting diode (LED) chip instead of a wide range CCD system.

  3. Online compensation for target motion with scanned particle beams: simulation environment.

    PubMed

    Li, Qiang; Groezinger, Sven Oliver; Haberer, Thomas; Rietzel, Eike; Kraft, Gerhard

    2004-07-21

    Target motion is one of the major limitations of each high precision radiation therapy. Using advanced active beam delivery techniques, such as the magnetic raster scanning system for particle irradiation, the interplay between time-dependent beam and target position heavily distorts the applied dose distribution. This paper presents a simulation environment in which the time-dependent effect of target motion on heavy-ion irradiation can be calculated with dynamically scanned ion beams. In an extension of the existing treatment planning software for ion irradiation of static targets (TRiP) at GSI, the expected dose distribution is calculated as the sum of several sub-distributions for single target motion states. To investigate active compensation for target motion by adapting the position of the therapeutic beam during irradiation, the planned beam positions can be altered during the calculation. Applying realistic parameters to the planned motion-compensation methods at GSI, the effect of target motion on the expected dose uniformity can be simulated for different target configurations and motion conditions. For the dynamic dose calculation, experimentally measured profiles of the beam extraction in time were used. Initial simulations show the feasibility and consistency of an active motion compensation with the magnetic scanning system and reveal some strategies to improve the dose homogeneity inside the moving target. The simulation environment presented here provides an effective means for evaluating the dose distribution for a moving target volume with and without motion compensation. It contributes a substantial basis for the experimental research on the irradiation of moving target volumes with scanned ion beams at GSI which will be presented in upcoming papers.

  4. Experimental evaluation of fog warning system.

    PubMed

    Al-Ghamdi, Ali S

    2007-11-01

    Highway safety is a major concern to the public and to transportation professionals, so the number of crashes caused by poor visibility due to fog form an alarming statistic. Drivers respond to poor visibility conditions in different ways: some slow down; others do not. Many drivers simply follow the taillights of the vehicle ahead. Accordingly, hazardous conditions are created in which speeds are both too high for the prevailing conditions and highly variable. Findings are presented from a study of traffic crashes due to fog in the southern region of Saudi Arabia. The primary objective was to assess the effectiveness of fog detection and warning system on driver behavior regarding speed and headway. This warning system includes visibility sensors that automatically activate a variable message sign that posts an advisory speed when hazardous conditions due to fog occur. The system was installed on a 2 km section of a two-lane, rural highway. A data set of 36,013 observations from both experimental and control sections at two study sites was collected and analyzed. The data included vehicle speed, volume, and classification; time headway, time of day, and visibility distance. Although the warning system was ineffective in reducing speed variability, mean speed throughout the experimental sections was reduced by about 6.5 kph. This reduction indicates that the warning system appeared to have a positive effect on driver behavior in fog even though the observed mean speeds were still higher than the posted advisory speed. From relationships found in the literature between mean driving speed and number of crashes, a speed reduction of only 5 kph would yield a 15% decrease in the number of crashes.

  5. Program for Experimentation With Expert Systems

    NASA Technical Reports Server (NTRS)

    Engle, S. W.

    1986-01-01

    CERBERUS is forward-chaining, knowledge-based system program useful for experimentation with expert systems. Inference-engine mechanism performs deductions according to user-supplied rule set. Information stored in intermediate area, and user interrogated only when no applicable data found in storage. Each assertion posed by CERBERUS answered with certainty ranging from 0 to 100 percent. Rule processor stops investigating applicable rules when goal reaches certainty of 95 percent or higher. Capable of operating for wide variety of domains. Sample rule files included for animal identification, pixel classification in image processing, and rudimentary car repair for novice mechanic. User supplies set of end goals or actions. System complexity decided by user's rule file. CERBERUS written in FORTRAN 77.

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

    NASA Technical Reports Server (NTRS)

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

    2010-01-01

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

  7. The application of carbon nanotubes in target drug delivery systems for cancer therapies

    NASA Astrophysics Data System (ADS)

    Zhang, Wuxu; Zhang, Zhenzhong; Zhang, Yingge

    2011-10-01

    Among all cancer treatment options, chemotherapy continues to play a major role in killing free cancer cells and removing undetectable tumor micro-focuses. Although chemotherapies are successful in some cases, systemic toxicity may develop at the same time due to lack of selectivity of the drugs for cancer tissues and cells, which often leads to the failure of chemotherapies. Obviously, the therapeutic effects will be revolutionarily improved if human can deliver the anticancer drugs with high selectivity to cancer cells or cancer tissues. This selective delivery of the drugs has been called target treatment. To realize target treatment, the first step of the strategies is to build up effective target drug delivery systems. Generally speaking, such a system is often made up of the carriers and drugs, of which the carriers play the roles of target delivery. An ideal carrier for target drug delivery systems should have three pre-requisites for their functions: (1) they themselves have target effects; (2) they have sufficiently strong adsorptive effects for anticancer drugs to ensure they can transport the drugs to the effect-relevant sites; and (3) they can release the drugs from them in the effect-relevant sites, and only in this way can the treatment effects develop. The transporting capabilities of carbon nanotubes combined with appropriate surface modifications and their unique physicochemical properties show great promise to meet the three pre-requisites. Here, we review the progress in the study on the application of carbon nanotubes as target carriers in drug delivery systems for cancer therapies.

  8. Experimental system for the control of surgically induced infections

    NASA Technical Reports Server (NTRS)

    1972-01-01

    The experimental system is described, and the procedures for surgery usage and maintenance are outlined. Basically the system consists of the following: (1) a portable clean room comprised of a horizontal laminar flow filter system and a transparent walled enclosure, (2) a helmet-shoulder pad assembly, (3) a communications system, (4) a helmet ventilation system, and (5) surgical gowns.

  9. An automatic target recognition system based on SAR image

    NASA Astrophysics Data System (ADS)

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

    2009-10-01

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

  10. Polymeric micelles with stimuli-triggering systems for advanced cancer drug targeting.

    PubMed

    Nakayama, Masamichi; Akimoto, Jun; Okano, Teruo

    2014-08-01

    Since the 1990s, nanoscale drug carriers have played a pivotal role in cancer chemotherapy, acting through passive drug delivery mechanisms and subsequent pharmaceutical action at tumor tissues with reduction of adverse effects. Polymeric micelles, as supramolecular assemblies of amphiphilic polymers, have been considerably developed as promising drug carrier candidates, and a number of clinical studies of anticancer drug-loaded polymeric micelle carriers for cancer chemotherapy applications are now in progress. However, these systems still face several issues; at present, the simultaneous control of target-selective delivery and release of incorporated drugs remains difficult. To resolve these points, the introduction of stimuli-responsive mechanisms to drug carrier systems is believed to be a promising approach to provide better solutions for future tumor drug targeting strategies. As possible trigger signals, biological acidic pH, light, heating/cooling and ultrasound actively play significant roles in signal-triggering drug release and carrier interaction with target cells. This review article summarizes several molecular designs for stimuli-responsive polymeric micelles in response to variation of pH, light and temperature and discusses their potentials as next-generation tumor drug targeting systems.

  11. Cnidarian Neurotoxic Peptides Affecting Central Nervous System Targets.

    PubMed

    Lazcano-Pérez, Fernando; Hernández-Guzmán, Ulises; Sánchez-Rodríguez, Judith; Arreguín-Espinosa, Roberto

    2016-01-01

    Natural products from animal venoms have been used widely in the discovery of novel molecules with particular biological activities that enable their use as potential drug candidates. The phylum Cnidaria (jellyfish, sea anemones, corals zoanthids, hydrozoans, etc.) is the most ancient venomous phylum on earth. Its venoms are composed of a complex mixture of peptidic compounds with neurotoxic and cytolitic properties that have shown activity on mammalian systems despite the fact that they are naturally targeted against fish and invertebrate preys, mainly crustaceans. For this reason, cnidarian venoms are an interesting and vast source of molecules with a remarkable activity on central nervous system, targeting mainly voltage-gated ion channels, ASIC channels, and TRPV1 receptors. In this brief review, we list the amino acid sequences of most cnidarian neurotoxic peptides reported to date. Additionally, we propose the inclusion of a new type of voltage-gated sea anemone sodium channel toxins based on the most recent reports.

  12. A real-time optical tracking and measurement processing system for flying targets.

    PubMed

    Guo, Pengyu; Ding, Shaowen; Zhang, Hongliang; Zhang, Xiaohu

    2014-01-01

    Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control.

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

    PubMed

    Jha, Ashwani; Shankar, Ravi

    2011-12-29

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

  14. Set membership experimental design for biological systems.

    PubMed

    Marvel, Skylar W; Williams, Cranos M

    2012-03-21

    Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. The practicability of our approach is illustrated with a case study. This study shows that our approach is able to 1) identify

  15. Set membership experimental design for biological systems

    PubMed Central

    2012-01-01

    Background Experimental design approaches for biological systems are needed to help conserve the limited resources that are allocated for performing experiments. The assumptions used when assigning probability density functions to characterize uncertainty in biological systems are unwarranted when only a small number of measurements can be obtained. In these situations, the uncertainty in biological systems is more appropriately characterized in a bounded-error context. Additionally, effort must be made to improve the connection between modelers and experimentalists by relating design metrics to biologically relevant information. Bounded-error experimental design approaches that can assess the impact of additional measurements on model uncertainty are needed to identify the most appropriate balance between the collection of data and the availability of resources. Results In this work we develop a bounded-error experimental design framework for nonlinear continuous-time systems when few data measurements are available. This approach leverages many of the recent advances in bounded-error parameter and state estimation methods that use interval analysis to generate parameter sets and state bounds consistent with uncertain data measurements. We devise a novel approach using set-based uncertainty propagation to estimate measurement ranges at candidate time points. We then use these estimated measurements at the candidate time points to evaluate which candidate measurements furthest reduce model uncertainty. A method for quickly combining multiple candidate time points is presented and allows for determining the effect of adding multiple measurements. Biologically relevant metrics are developed and used to predict when new data measurements should be acquired, which system components should be measured and how many additional measurements should be obtained. Conclusions The practicability of our approach is illustrated with a case study. This study shows that our

  16. Ice detection systems : experimental feature : final report.

    DOT National Transportation Integrated Search

    1986-01-01

    In the fall of 1980, an experimental ice detection system was installed on the Fremont Bridge in Portland, Oregon. this bridge, which caries I-405 over the Willamette River, has a history of icing problem when the deck is wet and the temperature hove...

  17. New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves.

    PubMed

    Tudorancea, Ionuț; Porumb, Vlad; Trandabăţ, Alexandru; Neaga, Decebal; Tamba, Bogdan; Iliescu, Radu; Dimofte, Gabriel M

    2017-01-01

    Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250-270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected. In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40-42°C and 42-44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments. We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia.

  18. A physics-based solver to optimize the illumination of cylindrical targets in spherically distributed high power laser systems.

    PubMed

    Gourdain, P-A

    2017-05-01

    In recent years, our understanding of high energy density plasmas has played an important role in improving inertial fusion confinement and in emerging new fields of physics, such as laboratory astrophysics. Every new idea required developing innovative experimental platforms at high power laser facilities, such as OMEGA or NIF. These facilities, designed to focus all their beams onto spherical targets or hohlraum windows, are now required to shine them on more complex targets. While the pointing on planar geometries is relatively straightforward, it becomes problematic for cylindrical targets or target with more complex geometries. This publication describes how the distribution of laser beams on a cylindrical target can be done simply by using a set of physical laws as a pointing procedure. The advantage of the method is threefold. First, it is straightforward, requiring no mathematical enterprise besides solving ordinary differential equations. Second, it will converge if a local optimum exists. Finally, it is computationally inexpensive. Experimental results show that this approach produces a geometrical beam distribution that yields cylindrically symmetric implosions.

  19. A physics-based solver to optimize the illumination of cylindrical targets in spherically distributed high power laser systems

    NASA Astrophysics Data System (ADS)

    Gourdain, P.-A.

    2017-05-01

    In recent years, our understanding of high energy density plasmas has played an important role in improving inertial fusion confinement and in emerging new fields of physics, such as laboratory astrophysics. Every new idea required developing innovative experimental platforms at high power laser facilities, such as OMEGA or NIF. These facilities, designed to focus all their beams onto spherical targets or hohlraum windows, are now required to shine them on more complex targets. While the pointing on planar geometries is relatively straightforward, it becomes problematic for cylindrical targets or target with more complex geometries. This publication describes how the distribution of laser beams on a cylindrical target can be done simply by using a set of physical laws as a pointing procedure. The advantage of the method is threefold. First, it is straightforward, requiring no mathematical enterprise besides solving ordinary differential equations. Second, it will converge if a local optimum exists. Finally, it is computationally inexpensive. Experimental results show that this approach produces a geometrical beam distribution that yields cylindrically symmetric implosions.

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

    NASA Astrophysics Data System (ADS)

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

    2013-09-01

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

  1. Radioactive by-products of a self-shielded cyclotron and the liquid target system for F-18 routine production.

    PubMed

    Kambali, I; Suryanto, H; Parwanto

    2016-06-01

    Routine production of F-18 radionuclide using proton beams accelerated in a cyclotron could potentially generate residual radioisotopes in the cyclotron vicinity which eventually become major safety concerns over radiation exposure to the workers. In this investigation, a typical 11-MeV proton, self-shielded cyclotron has been assessed for its residual radiation sources in the cyclotron's shielding, tank/chamber, cave wall as well as target system. Using a portable gamma ray spectroscopy system, the radiation measurement in the cyclotron environment has been carried out. Experimental results indicate that relatively long-lived radioisotopes such as Mn-54, Zn-65 and Eu-152 are detected in the inner and outer surface of the cyclotron shielding respectively while Mn-54 spectrum is observed around the cyclotron chamber. Weak intensity of Eu-152 radioisotope is again spotted in the inner and outer surface of the cyclotron cave wall. Angular distribution measurement of the Eu-152 shows that the intensity slightly drops with increasing observation angle relative to the proton beam incoming angle. In the target system, gamma rays from Co-56, Mn-52, Co-60, Mn-54, Ag-110 m are identified. TALYS-calculated nuclear cross-section data are used to study the origins of the radioactive by-products.

  2. Review article: the endocannabinoid system in liver disease, a potential therapeutic target.

    PubMed

    Basu, P P; Aloysius, M M; Shah, N J; Brown, R S

    2014-04-01

    Endocannabinoids are a family of potent lipid-soluble molecules, acting on the cannabinoid (CB) receptors that mediate the effects of marijuana. The CB receptors, endocannabinoids and the enzymes involved in their synthesis and degradation are located in the brain and peripheral tissues, including the liver. To review the current understanding of the role of the endocannabinoid system in liver disease-associated pathophysiological conditions, and drugs targeting the endocannabinoid system as therapy for liver disease. Original articles and reviews were used to summarise the relevant pre-clinical and clinical research findings relating to this topic. The endocannabinoid system as a whole plays an important role in liver diseases (i.e. non-alcoholic liver disease, alcoholic liver disease, hepatic encephalopathy and autoimmune hepatitis) and related pathophysiological conditions (i.e. altered hepatic haemodynamics, cirrhotic cardiomyopathy, metabolic syndrome and ischaemia/reperfusion disease). Pharmacological targeting of the endocannabinoid system has had success as treatment for patients with liver disease, but adverse events led to withdrawal of marketing approval. However, there is optimism over novel therapeutics targeting the endocannabinoid system currently in the pre-clinical stage of development. The endocannabinoid system plays an important role in the pathophysiology of liver disease and its associated conditions. While some drugs targeting the endocannabinoid system have deleterious neurological adverse events, there is promise for a newer generation of therapies that do not cross the blood-brain barrier. © 2014 John Wiley & Sons Ltd.

  3. The application of antitumor drug-targeting models on liver cancer.

    PubMed

    Yan, Yan; Chen, Ningbo; Wang, Yunbing; Wang, Ke

    2016-06-01

    Hepatocarcinoma animal models, such as the induced tumor model, transplanted tumor model, gene animal model, are significant experimental tools for the evaluation of targeting drug delivery system as well as the pre-clinical studies of liver cancer. The application of antitumor drug-targeting models not only furnishes similar biological characteristics to human liver cancer but also offers guarantee of pharmacokinetic indicators of the liver-targeting preparations. In this article, we have reviewed some kinds of antitumor drug-targeting models of hepatoma and speculated that the research on this field would be capable of attaining a deeper level and expecting a superior achievement in the future.

  4. Experimental and statistical post-validation of positive example EST sequences carrying peroxisome targeting signals type 1 (PTS1).

    PubMed

    Lingner, Thomas; Kataya, Amr R A; Reumann, Sigrun

    2012-02-01

    We recently developed the first algorithms specifically for plants to predict proteins carrying peroxisome targeting signals type 1 (PTS1) from genome sequences. As validated experimentally, the prediction methods are able to correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel PTS1 tripeptides. The high prediction performance is primarily determined by the large number and sequence diversity of the underlying positive example sequences, which mainly derived from EST databases. However, a few constructs remained cytosolic in experimental validation studies, indicating sequencing errors in some ESTs. To identify erroneous sequences, we validated subcellular targeting of additional positive example sequences in the present study. Moreover, we analyzed the distribution of prediction scores separately for each orthologous group of PTS1 proteins, which generally resembled normal distributions with group-specific mean values. The cytosolic sequences commonly represented outliers of low prediction scores and were located at the very tail of a fitted normal distribution. Three statistical methods for identifying outliers were compared in terms of sensitivity and specificity." Their combined application allows elimination of erroneous ESTs from positive example data sets. This new post-validation method will further improve the prediction accuracy of both PTS1 and PTS2 protein prediction models for plants, fungi, and mammals.

  5. Experimental and statistical post-validation of positive example EST sequences carrying peroxisome targeting signals type 1 (PTS1)

    PubMed Central

    Lingner, Thomas; Kataya, Amr R. A.; Reumann, Sigrun

    2012-01-01

    We recently developed the first algorithms specifically for plants to predict proteins carrying peroxisome targeting signals type 1 (PTS1) from genome sequences.1 As validated experimentally, the prediction methods are able to correctly predict unknown peroxisomal Arabidopsis proteins and to infer novel PTS1 tripeptides. The high prediction performance is primarily determined by the large number and sequence diversity of the underlying positive example sequences, which mainly derived from EST databases. However, a few constructs remained cytosolic in experimental validation studies, indicating sequencing errors in some ESTs. To identify erroneous sequences, we validated subcellular targeting of additional positive example sequences in the present study. Moreover, we analyzed the distribution of prediction scores separately for each orthologous group of PTS1 proteins, which generally resembled normal distributions with group-specific mean values. The cytosolic sequences commonly represented outliers of low prediction scores and were located at the very tail of a fitted normal distribution. Three statistical methods for identifying outliers were compared in terms of sensitivity and specificity.” Their combined application allows elimination of erroneous ESTs from positive example data sets. This new post-validation method will further improve the prediction accuracy of both PTS1 and PTS2 protein prediction models for plants, fungi, and mammals. PMID:22415050

  6. Toward Optimal Target Placement for Neural Prosthetic Devices

    PubMed Central

    Cunningham, John P.; Yu, Byron M.; Gilja, Vikash; Ryu, Stephen I.; Shenoy, Krishna V.

    2008-01-01

    Neural prosthetic systems have been designed to estimate continuous reach trajectories (motor prostheses) and to predict discrete reach targets (communication prostheses). In the latter case, reach targets are typically decoded from neural spiking activity during an instructed delay period before the reach begins. Such systems use targets placed in radially symmetric geometries independent of the tuning properties of the neurons available. Here we seek to automate the target placement process and increase decode accuracy in communication prostheses by selecting target locations based on the neural population at hand. Motor prostheses that incorporate intended target information could also benefit from this consideration. We present an optimal target placement algorithm that approximately maximizes decode accuracy with respect to target locations. In simulated neural spiking data fit from two monkeys, the optimal target placement algorithm yielded statistically significant improvements up to 8 and 9% for two and sixteen targets, respectively. For four and eight targets, gains were more modest, as the target layouts found by the algorithm closely resembled the canonical layouts. We trained a monkey in this paradigm and tested the algorithm with experimental neural data to confirm some of the results found in simulation. In all, the algorithm can serve not only to create new target layouts that outperform canonical layouts, but it can also confirm or help select among multiple canonical layouts. The optimal target placement algorithm developed here is the first algorithm of its kind, and it should both improve decode accuracy and help automate target placement for neural prostheses. PMID:18829845

  7. An Archaeal Immune System Can Detect Multiple Protospacer Adjacent Motifs (PAMs) to Target Invader DNA*

    PubMed Central

    Fischer, Susan; Maier, Lisa-Katharina; Stoll, Britta; Brendel, Jutta; Fischer, Eike; Pfeiffer, Friedhelm; Dyall-Smith, Mike; Marchfelder, Anita

    2012-01-01

    The clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated (Cas) system provides adaptive and heritable immunity against foreign genetic elements in most archaea and many bacteria. Although this system is widespread and diverse with many subtypes, only a few species have been investigated to elucidate the precise mechanisms for the defense of viruses or plasmids. Approximately 90% of all sequenced archaea encode CRISPR/Cas systems, but their molecular details have so far only been examined in three archaeal species: Sulfolobus solfataricus, Sulfolobus islandicus, and Pyrococcus furiosus. Here, we analyzed the CRISPR/Cas system of Haloferax volcanii using a plasmid-based invader assay. Haloferax encodes a type I-B CRISPR/Cas system with eight Cas proteins and three CRISPR loci for which the identity of protospacer adjacent motifs (PAMs) was unknown until now. We identified six different PAM sequences that are required upstream of the protospacer to permit target DNA recognition. This is only the second archaeon for which PAM sequences have been determined, and the first CRISPR group with such a high number of PAM sequences. Cells could survive the plasmid challenge if their CRISPR/Cas system was altered or defective, e.g. by deletion of the cas gene cassette. Experimental PAM data were supplemented with bioinformatics data on Haloferax and Haloquadratum. PMID:22767603

  8. A Tupaia paramyxovirus vector system for targeting and transgene expression.

    PubMed

    Engeland, Christine E; Bossow, Sascha; Hudacek, Andrew W; Hoyler, Birgit; Förster, Judith; Veinalde, Rūta; Jäger, Dirk; Cattaneo, Roberto; Ungerechts, Guy; Springfeld, Christoph

    2017-09-01

    Viruses from the diverse family of Paramyxoviridae include important pathogens and are applied in gene therapy and for cancer treatment. The Tupaia paramyxovirus (TPMV), isolated from the kidney of a tree shrew, does not infect human cells and neutralizing antibodies against other Paramyxoviridae do not cross-react with TPMV. Here, we present a vector system for de novo generation of infectious TPMV that allows for insertion of additional genes as well as targeting using antibody single-chain variable fragments. We show that the recombinant TPMV specifically infect cells expressing the targeted receptor and replicate in human cells. This vector system provides a valuable tool for both basic research and therapeutic applications.

  9. Whole-ecosystem experimental manipulations of tropical forests.

    PubMed

    Fayle, Tom M; Turner, Edgar C; Basset, Yves; Ewers, Robert M; Reynolds, Glen; Novotny, Vojtech

    2015-06-01

    Tropical forests are highly diverse systems involving extraordinary numbers of interactions between species, with each species responding in a different way to the abiotic environment. Understanding how these systems function and predicting how they respond to anthropogenic global change is extremely challenging. We argue for the necessity of 'whole-ecosystem' experimental manipulations, in which the entire ecosystem is targeted, either to reveal the functioning of the system in its natural state or to understand responses to anthropogenic impacts. We survey the current range of whole-ecosystem manipulations, which include those targeting weather and climate, nutrients, biotic interactions, human impacts, and habitat restoration. Finally we describe the unique challenges and opportunities presented by such projects and suggest directions for future experiments. Copyright © 2015 The Authors. Published by Elsevier Ltd.. All rights reserved.

  10. Photoacoustic Experimental System to Confirm Infrared Absorption Due to Greenhouse Gases

    ERIC Educational Resources Information Center

    Kaneko, Fumitoshi; Monjushiro, Hideaki; Nishiyama, Masayoshi; Kasai, Toshio; Harris, Harold H.

    2010-01-01

    An experimental system for detecting infrared absorption using the photoacoustic (PA) effect is described. It is aimed for use at high-school level to illustrate the difference in infrared (IR) absorption among the gases contained in the atmosphere in connection with the greenhouse effect. The experimental system can be built with readily…

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

    PubMed

    Bandyopadhyay, Sanghamitra; Mitra, Ramkrishna

    2009-10-15

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

  12. Effects of pre-experimental knowledge on recognition memory.

    PubMed

    Bird, Chris M; Davies, Rachel A; Ward, Jamie; Burgess, Neil

    2011-01-01

    The influence of pre-experimental autobiographical knowledge on recognition memory was investigated using as memoranda faces that were either personally known or unknown to the participant. Under a dual process theory, such knowledge boosted both recollection- and familiarity-based recognition judgements. Under an unequal variance signal detection model, pre-experimental knowledge increased both the variance and the separation of the target and foil memory strength distributions, boosting hits and correct rejections. Thus, pre-experimental knowledge has profound effects on the multiple, interacting processes that subserve recognition memory, and likely in the neural systems that underpin them.

  13. A Real-Time Optical Tracking and Measurement Processing System for Flying Targets

    PubMed Central

    Guo, Pengyu; Ding, Shaowen; Zhang, Hongliang; Zhang, Xiaohu

    2014-01-01

    Optical tracking and measurement for flying targets is unlike the close range photography under a controllable observation environment, which brings extreme conditions like diverse target changes as a result of high maneuver ability and long cruising range. This paper first designed and realized a distributed image interpretation and measurement processing system to achieve resource centralized management, multisite simultaneous interpretation and adaptive estimation algorithm selection; then proposed a real-time interpretation method which contains automatic foreground detection, online target tracking, multiple features location, and human guidance. An experiment is carried out at performance and efficiency evaluation of the method by semisynthetic video. The system can be used in the field of aerospace tests like target analysis including dynamic parameter, transient states, and optical physics characteristics, with security control. PMID:24987748

  14. An experimental study of ammonia borane based hydrogen storage systems

    NASA Astrophysics Data System (ADS)

    Deshpande, Kedaresh A.

    2011-12-01

    Hydrogen is a promising fuel for the future, capable of meeting the demands of energy storage and low pollutant emission. Chemical hydrides are potential candidates for chemical hydrogen storage, especially for automobile applications. Ammonia borane (AB) is a chemical hydride being investigated widely for its potential to realize the hydrogen economy. In this work, the yield of hydrogen obtained during neat AB thermolysis was quantified using two reactor systems. First, an oil bath heated glass reactor system was used with AB batches of 0.13 gram (+/- 0.001 gram). The rates of hydrogen generation were measured. Based on these experimental data, an electrically heated steel reactor system was designed and constructed to handle up to 2 grams of AB per batch. A majority of components were made of stainless-steel. The system consisted of an AB reservoir and feeder, a heated reactor, a gas processing unit and a system control and monitoring unit. An electronic data acquisition system was used to record experimental data. The performance of the steel reactor system was evaluated experimentally through batch reactions of 30 minutes each, for reaction temperatures in the range from 373 K to 430 K. The experimental data showed exothermic decomposition of AB accompanied by rapid generation of hydrogen during the initial period of the reaction. 90% of the hydrogen was generated during the initial 120 seconds after addition of AB to the reactor. At 430 K, the reaction produced 12 wt.% of hydrogen. The heat diffusion in the reactor system and the process of exothermic decomposition of AB were coupled in a two-dimensional model. Neat AB thermolysis was modeled as a global first order reactions based on Arrhenius theory. The values of equation constants were derived from curve fit of experimental data. The pre-exponential constant and the activation energy were estimated to be 4 s-1 (+/- 0.4 s-1) and 13000 J mol -1 s-1 (+/- 1050 J mol-1 s -1) respectively. The model was solved

  15. Novel Therapeutic Targets for Phosphodiesterase 5 Inhibitors: current state-of-the-art on systemic arterial hypertension and atherosclerosis.

    PubMed

    Vasquez, Elisardo C; Gava, Agata L; Graceli, Jones B; Balarini, Camille M; Campagnaro, Bianca P; Pereira, Thiago Melo C; Meyrelles, Silvana S

    2016-01-01

    The usefulness of selective inhibitors of phosphodiesterase 5 (PDE5) is well known, first for the treatment of male erectile dysfunction and more recently for pulmonary hypertension. The discovery that PDE5 is present in the systemic artery endothelium and smooth muscle cells led investigators to test the extra sexual effects of sildenafil, the first and most investigated PDE5 inhibitor, in diseases affecting the systemic arteries. Cumulative data from experimental and clinical studies have revealed beneficial effects of sildenafil on systemic arterial hypertension and its target organs, such as the heart, kidneys and vasculature. An important effect of sildenafil is reduction of hypertension and improvement of endothelial function in experimental models of hypertension and hypertensive subjects. Interestingly, in angiotensin-dependent hypertension, its beneficial effects on endothelial and kidney dysfunctions seem to at least in part be caused by its ability to decrease the levels of angiotensin II and increase angiotensin 1-7, in addition to improving nitric oxide bioavailability and diminishing reactive oxygen species. Another remarkable finding on the effects of sildenafil comes from studies in apolipoprotein E knockout mice, a model of atherosclerosis that closely resembles human atherosclerotic disease. In this review, we focus on the promising beneficial effects of sildenafil for treating systemic high blood pressure, especially resistant hypertension, and the endothelial dysfunction that is present in hypertension and atherosclerosis.

  16. Drug-targeting methodologies with applications: A review

    PubMed Central

    Kleinstreuer, Clement; Feng, Yu; Childress, Emily

    2014-01-01

    Targeted drug delivery to solid tumors is a very active research area, focusing mainly on improved drug formulation and associated best delivery methods/devices. Drug-targeting has the potential to greatly improve drug-delivery efficacy, reduce side effects, and lower the treatment costs. However, the vast majority of drug-targeting studies assume that the drug-particles are already at the target site or at least in its direct vicinity. In this review, drug-delivery methodologies, drug types and drug-delivery devices are discussed with examples in two major application areas: (1) inhaled drug-aerosol delivery into human lung-airways; and (2) intravascular drug-delivery for solid tumor targeting. The major problem addressed is how to deliver efficiently the drug-particles from the entry/infusion point to the target site. So far, most experimental results are based on animal studies. Concerning pulmonary drug delivery, the focus is on the pros and cons of three inhaler types, i.e., pressurized metered dose inhaler, dry powder inhaler and nebulizer, in addition to drug-aerosol formulations. Computational fluid-particle dynamics techniques and the underlying methodology for a smart inhaler system are discussed as well. Concerning intravascular drug-delivery for solid tumor targeting, passive and active targeting are reviewed as well as direct drug-targeting, using optimal delivery of radioactive microspheres to liver tumors as an example. The review concludes with suggestions for future work, considereing both pulmonary drug targeting and direct drug delivery to solid tumors in the vascular system. PMID:25516850

  17. Experimental violation of Bell inequalities for multi-dimensional systems

    PubMed Central

    Lo, Hsin-Pin; Li, Che-Ming; Yabushita, Atsushi; Chen, Yueh-Nan; Luo, Chih-Wei; Kobayashi, Takayoshi

    2016-01-01

    Quantum correlations between spatially separated parts of a d-dimensional bipartite system (d ≥ 2) have no classical analog. Such correlations, also called entanglements, are not only conceptually important, but also have a profound impact on information science. In theory the violation of Bell inequalities based on local realistic theories for d-dimensional systems provides evidence of quantum nonlocality. Experimental verification is required to confirm whether a quantum system of extremely large dimension can possess this feature, however it has never been performed for large dimension. Here, we report that Bell inequalities are experimentally violated for bipartite quantum systems of dimensionality d = 16 with the usual ensembles of polarization-entangled photon pairs. We also estimate that our entanglement source violates Bell inequalities for extremely high dimensionality of d > 4000. The designed scenario offers a possible new method to investigate the entanglement of multipartite systems of large dimensionality and their application in quantum information processing. PMID:26917246

  18. Interactive display system having a scaled virtual target zone

    DOEpatents

    Veligdan, James T.; DeSanto, Leonard

    2006-06-13

    A display system includes a waveguide optical panel having an inlet face and an opposite outlet face. A projector and imaging device cooperate with the panel for projecting a video image thereon. An optical detector bridges at least a portion of the waveguides for detecting a location on the outlet face within a target zone of an inbound light spot. A controller is operatively coupled to the imaging device and detector for displaying a cursor on the outlet face corresponding with the detected location of the spot within the target zone.

  19. Experimental evaluation of the performance of pulsed two-color laser-ranging systems

    NASA Technical Reports Server (NTRS)

    Im, Kwaifong E.; Gardner, Chester S.; Abshire, James B.; Mcgarry, Jan F.

    1987-01-01

    Two-color laser-ranging systems can be used to estimate the atmospheric delay by measuring the difference in propagation times between two optical pulses transmitted at different wavelengths. This paper describes horizontal-path ranging experiments that were conducted using flat diffuse targets and cube-corner reflector arrays. Measurements of the timing accuracy of the cross-correlation estimator, atmospheric delay, received pulse shapes, and signal power spectra are presented. The results are in general agreement with theory and indicate that target speckle can be the dominant noise source when the target is small and is located far from the ranging system or when the target consists of a small number of cube-corner reflectors.

  20. Endocannabinoid System: A Multi-Facet Therapeutic Target.

    PubMed

    Kaur, Rimplejeet; Ambwani, Sneha R; Singh, Surjit

    2016-01-01

    the therapeutic targets for both cannabinoid receptor agonists and antagonists. One challenge is to develop drugs that target only cannabinoid receptors in a particular tissue and another is to invent drugs that act selectively on cannabinoid receptors located outside the blood brain barrier. Besides this, development of the suitable dosage forms with maximum efficacy and minimum adverse effects is also warranted. Another angle to be introspected for therapeutic abilities of this group of drugs is non-CB1 and non-CB2 receptor targets for cannabinoids. In order to successfully exploit the therapeutic potential of endocannabinoid system, it is imperative to further characterize the endocannabinoid system in terms of identification of the exact cellular location of cannabinoid receptors and their role as "protective" and "disease inducing substance", time-dependent changes in the expression of cannabinoid receptors.

  1. HIV-1 Proteins, Tat and gp120, Target the Developing Dopamine System

    PubMed Central

    Fitting, Sylvia; Booze, Rosemarie M.; Mactutus, Charles F.

    2015-01-01

    In 2014, 3.2 million children (< 15 years of age) were estimated to be living with HIV and AIDS worldwide, with the 240,000 newly infected children in the past year, i.e., another child infected approximately every two minutes [1]. The primary mode of HIV infection is through mother-to-child transmission (MTCT), occurring either in utero, intrapartum, or during breastfeeding. The effects of HIV-1 on the central nervous system (CNS) are putatively accepted to be mediated, in part, via viral proteins, such as Tat and gp120. The current review focuses on the targets of HIV-1 proteins during the development of the dopamine (DA) system, which appears to be specifically susceptible in HIV-1-infected children. Collectively, the data suggest that the DA system is a clinically relevant target in chronic HIV-1 infection, is one of the major targets in pediatric HIV-1 CNS infection, and may be specifically susceptible during development. The present review discusses the development of the DA system, follows the possible targets of the HIV-1 proteins during the development of the DA system, and suggests potential therapeutic approaches. By coupling our growing understanding of the development of the CNS with the pronounced age-related differences in disease progression, new light may be shed on the neurological and neurocognitive deficits that follow HIV-1 infection. PMID:25613135

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

    PubMed

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

    2016-01-01

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

  3. The role of the vestibular system in manual target localization

    NASA Technical Reports Server (NTRS)

    Barry, Susan R.; Mueller, S. Alyssa

    1995-01-01

    Astronauts experience perceptual and sensory-motor disturbances during spaceflight and immediately after return to the 1-g environment of Earth. During spaceflight, sensory information from the eyes, limbs and vestibular organs is reinterpreted by the central nervous system so that astronauts can produce appropriate body movements in microgravity. Alterations in sensory-motor function may affect eye-head-hand coordination and, thus, the crewmember's ability to manually locate objects in extrapersonal space. Previous reports have demonstrated that crewmembers have difficulty in estimating joint and limb position and in pointing to memorized target positions on orbit and immediately postflight. One set of internal cues that may assist in the manual localization of objects is information from the vestibular system. This system contributes to our sense of the body's position in space by providing information on head position and movement and the orientation of the body with respect to gravity. Research on the vestibular system has concentrated on its role in oculo-motor control. Little is known about the role that vestibular information plays in manual motor control, such as reaching and pointing movements. Since central interpretation of vestibular information is altered in microgravity, it is important to determine its role in this process. This summer, we determined the importance of vestibular information in a subject's ability to point accurately toward a target in extrapersonal space. Subjects were passively rotated across the earth-vertical axis and then asked to point back to a previously-seen target. In the first paradigm, the subjects used both visual and vestibular cues for the pointing response, while, in the second paradigm, subjects used only vestibular information. Subjects were able to point with 85 percent accuracy to a target using vestibular information alone. We infer from this result that vestibular input plays a role in the spatial programming of

  4. Improvements of the target lifetime in the RHIC polarimeter

    NASA Astrophysics Data System (ADS)

    Steski, D. B.; Huang, H.; Kewisch, J.; Sukhanova, L.; Zelenski, A.

    2018-05-01

    The Relativistic Heavy Ion Collider (RHIC) at Brookhaven National Laboratory (BNL) is the only collider in the world to collide polarized protons. It is critical to the RHIC experimental program that the polarization of the proton beam is measured. This is accomplished with the Coulomb Nuclear Interference (CNI) polarimeter. The targets used in the RHIC CNI polarimeter are 50 nm thick, 25 mm long and <10 µm wide. As the beam intensity in RHIC has increased and the beam size has decreased, the lifetime of these targets has decreased dramatically. During the 2013 polarized proton experimental run, the targets needed to be replaced twice. This resulted in additional work and lost beam time. Before the 2015 experimental run, metal shields were installed around the ends of the targets which greatly improved the target lifetime. The results from the 2015 experimental run and plans for the 2017 experimental run will be discussed.

  5. Drug repurposing to target Ebola virus replication and virulence using structural systems pharmacology.

    PubMed

    Zhao, Zheng; Martin, Che; Fan, Raymond; Bourne, Philip E; Xie, Lei

    2016-02-18

    The recent outbreak of Ebola has been cited as the largest in history. Despite this global health crisis, few drugs are available to efficiently treat Ebola infections. Drug repurposing provides a potentially efficient solution to accelerating the development of therapeutic approaches in response to Ebola outbreak. To identify such candidates, we use an integrated structural systems pharmacology pipeline which combines proteome-scale ligand binding site comparison, protein-ligand docking, and Molecular Dynamics (MD) simulation. One thousand seven hundred and sixty-six FDA-approved drugs and 259 experimental drugs were screened to identify those with the potential to inhibit the replication and virulence of Ebola, and to determine the binding modes with their respective targets. Initial screening has identified a number of promising hits. Notably, Indinavir; an HIV protease inhibitor, may be effective in reducing the virulence of Ebola. Additionally, an antifungal (Sinefungin) and several anti-viral drugs (e.g. Maraviroc, Abacavir, Telbivudine, and Cidofovir) may inhibit Ebola RNA-directed RNA polymerase through targeting the MTase domain. Identification of safe drug candidates is a crucial first step toward the determination of timely and effective therapeutic approaches to address and mitigate the impact of the Ebola global crisis and future outbreaks of pathogenic diseases. Further in vitro and in vivo testing to evaluate the anti-Ebola activity of these drugs is warranted.

  6. A computational framework for modeling targets as complex adaptive systems

    NASA Astrophysics Data System (ADS)

    Santos, Eugene; Santos, Eunice E.; Korah, John; Murugappan, Vairavan; Subramanian, Suresh

    2017-05-01

    Modeling large military targets is a challenge as they can be complex systems encompassing myriad combinations of human, technological, and social elements that interact, leading to complex behaviors. Moreover, such targets have multiple components and structures, extending across multiple spatial and temporal scales, and are in a state of change, either in response to events in the environment or changes within the system. Complex adaptive system (CAS) theory can help in capturing the dynamism, interactions, and more importantly various emergent behaviors, displayed by the targets. However, a key stumbling block is incorporating information from various intelligence, surveillance and reconnaissance (ISR) sources, while dealing with the inherent uncertainty, incompleteness and time criticality of real world information. To overcome these challenges, we present a probabilistic reasoning network based framework called complex adaptive Bayesian Knowledge Base (caBKB). caBKB is a rigorous, overarching and axiomatic framework that models two key processes, namely information aggregation and information composition. While information aggregation deals with the union, merger and concatenation of information and takes into account issues such as source reliability and information inconsistencies, information composition focuses on combining information components where such components may have well defined operations. Since caBKBs can explicitly model the relationships between information pieces at various scales, it provides unique capabilities such as the ability to de-aggregate and de-compose information for detailed analysis. Using a scenario from the Network Centric Operations (NCO) domain, we will describe how our framework can be used for modeling targets with a focus on methodologies for quantifying NCO performance metrics.

  7. Analytical and experimental vibration analysis of a faulty gear system

    NASA Astrophysics Data System (ADS)

    Choy, F. K.; Braun, M. J.; Polyshchuk, V.; Zakrajsek, J. J.; Townsend, D. P.; Handschuh, R. F.

    1994-10-01

    A comprehensive analytical procedure was developed for predicting faults in gear transmission systems under normal operating conditions. A gear tooth fault model is developed to simulate the effects of pitting and wear on the vibration signal under normal operating conditions. The model uses changes in the gear mesh stiffness to simulate the effects of gear tooth faults. The overall dynamics of the gear transmission system is evaluated by coupling the dynamics of each individual gear-rotor system through gear mesh forces generated between each gear-rotor system and the bearing forces generated between the rotor and the gearbox structures. The predicted results were compared with experimental results obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. The Wigner-Ville Distribution (WVD) was used to give a comprehensive comparison of the predicted and experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD's ability to detect the pitting damage, and to determine its relative performance. Overall results show good correlation between the experimental vibration data of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

  8. Analytical and experimental vibration analysis of a faulty gear system

    NASA Astrophysics Data System (ADS)

    Choy, F. K.; Braun, M. J.; Polyshchuk, V.; Zakrajsek, J. J.; Townsend, D. P.; Handschuh, R. F.

    1994-10-01

    A comprehensive analytical procedure was developed for predicting faults in gear transmission systems under normal operating conditions. A gear tooth fault model is developed to simulate the effects of pitting and wear on the vibration signal under normal operating conditions. The model uses changes in the gear mesh stiffness to simulate the effects of gear tooth faults. The overall dynamics of the gear transmission system is evaluated by coupling the dynamics of each individual gear-rotor system through gear mesh forces generated between each gear-rotor system and the bearing forces generated between the rotor and the gearbox structure. The predicted results were compared with experimental results obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. The Wigner-Ville distribution (WVD) was used to give a comprehensive comparison of the predicted and experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD's ability to detect the pitting damage, and to determine its relative performance. Overall results show good correlation between the experimental vibration data of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

  9. Analytical and Experimental Vibration Analysis of a Faulty Gear System

    NASA Technical Reports Server (NTRS)

    Choy, F. K.; Braun, M. J.; Polyshchuk, V.; Zakrajsek, J. J.; Townsend, D. P.; Handschuh, R. F.

    1994-01-01

    A comprehensive analytical procedure was developed for predicting faults in gear transmission systems under normal operating conditions. A gear tooth fault model is developed to simulate the effects of pitting and wear on the vibration signal under normal operating conditions. The model uses changes in the gear mesh stiffness to simulate the effects of gear tooth faults. The overall dynamics of the gear transmission system is evaluated by coupling the dynamics of each individual gear-rotor system through gear mesh forces generated between each gear-rotor system and the bearing forces generated between the rotor and the gearbox structure. The predicted results were compared with experimental results obtained from a spiral bevel gear fatigue test rig at NASA Lewis Research Center. The Wigner-Ville distribution (WVD) was used to give a comprehensive comparison of the predicted and experimental results. The WVD method applied to the experimental results were also compared to other fault detection techniques to verify the WVD's ability to detect the pitting damage, and to determine its relative performance. Overall results show good correlation between the experimental vibration data of the damaged test gear and the predicted vibration from the model with simulated gear tooth pitting damage. Results also verified that the WVD method can successfully detect and locate gear tooth wear and pitting damage.

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

    NASA Astrophysics Data System (ADS)

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

    2017-04-01

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

  11. The influence of the earth radiation on space target detection system

    NASA Astrophysics Data System (ADS)

    Su, Xiaofeng; Chen, FanSheng; Cuikun, .; Liuyan, .

    2017-05-01

    In the view of space remote sensing such as satellite detection space debris detection etc. visible band is usually used in order to have the all-weather detection capability, long wavelength infrared (LWIR) detection is also an important supplement. However, in the tow wave band, the earth can be a very strong interference source, especially in the dim target detecting. When the target is close to the earth, especially the LEO target, the background radiation of the earth will also enter into the baffle, and became the stray light through reflection, the stray light can reduce the signal to clutter ratio (SCR) of the target and make it difficult to be detected. In the visible band, the solar albedo by the earth is the main clutter source while in the LWIR band the radiation of the earth is the main clutter source. So, in this paper, we establish the energy transformation from the earth background radiation to the detection system to assess the effects of the stray light. Firstly, we discretize the surface of the earth to different unit, and using MODTRAN to calculate the radiation of the discrete point in different light and climate conditions, then, we integral all the radiation which can reach the baffle in the same observation angles to get the energy distribution, finally, according the target energy and the non-uniformity of the detector, we can calculate the design requirement of the system stray light suppression, which provides the design basis for the optical system.

  12. Drug Targeting and Biomarkers in Head and Neck Cancers: Insights from Systems Biology Analyses.

    PubMed

    Islam, Tania; Rahman, Rezanur; Gov, Esra; Turanli, Beste; Gulfidan, Gizem; Haque, Anwarul; Arga, Kazım Yalçın; Haque Mollah, Nurul

    2018-06-01

    The head and neck squamous cell carcinoma (HNSCC) is one of the most common cancers in the world, but robust biomarkers and diagnostics are still not available. This study provides in-depth insights from systems biology analyses to identify molecular biomarker signatures to inform systematic drug targeting in HNSCC. Gene expression profiles from tumors and normal tissues of 22 patients with histological confirmation of nonmetastatic HNSCC were subjected to integrative analyses with genome-scale biomolecular networks (i.e., protein-protein interaction and transcriptional and post-transcriptional regulatory networks). We aimed to discover molecular signatures at RNA and protein levels, which could serve as potential drug targets for therapeutic innovation in the future. Eleven proteins, 5 transcription factors, and 20 microRNAs (miRNAs) came into prominence as potential drug targets. The differential expression profiles of these reporter biomolecules were cross-validated by independent RNA-Seq and miRNA-Seq datasets, and risk discrimination performance of the reporter biomolecules, BLNK, CCL2, E4F1, FOSL1, ISG15, MMP9, MYCN, MYH11, miR-1252, miR-29b, miR-29c, miR-3610, miR-431, and miR-523, was also evaluated. Using the transcriptome guided drug repositioning tool, geneXpharma, several candidate drugs were repurposed, including antineoplastic agents (e.g., gemcitabine and irinotecan), antidiabetics (e.g., rosiglitazone), dermatological agents (e.g., clocortolone and acitretin), and antipsychotics (e.g., risperidone), and binding affinities of the drugs to their potential targets were assessed using molecular docking analyses. The molecular signatures and repurposed drugs presented in this study warrant further attention for experimental studies since they offer significant potential as biomarkers and candidate therapeutics for precision medicine approaches to clinical management of HNSCC.

  13. Comprehensive target populations for current active safety systems using national crash databases.

    PubMed

    Kusano, Kristofer D; Gabler, Hampton C

    2014-01-01

    The objective of active safety systems is to prevent or mitigate collisions. A critical component in the design of active safety systems is the identification of the target population for a proposed system. The target population for an active safety system is that set of crashes that a proposed system could prevent or mitigate. Target crashes have scenarios in which the sensors and algorithms would likely activate. For example, the rear-end crash scenario, where the front of one vehicle contacts another vehicle traveling in the same direction and in the same lane as the striking vehicle, is one scenario for which forward collision warning (FCW) would be most effective in mitigating or preventing. This article presents a novel set of precrash scenarios based on coded variables from NHTSA's nationally representative crash databases in the United States. Using 4 databases (National Automotive Sampling System-General Estimates System [NASS-GES], NASS Crashworthiness Data System [NASS-CDS], Fatality Analysis Reporting System [FARS], and National Motor Vehicle Crash Causation Survey [NMVCCS]) the scenarios developed in this study can be used to quantify the number of police-reported crashes, seriously injured occupants, and fatalities that are applicable to proposed active safety systems. In this article, we use the precrash scenarios to identify the target populations for FCW, pedestrian crash avoidance systems (PCAS), lane departure warning (LDW), and vehicle-to-vehicle (V2V) or vehicle-to-infrastructure (V2I) systems. Crash scenarios were derived using precrash variables (critical event, accident type, precrash movement) present in all 4 data sources. This study found that these active safety systems could potentially mitigate approximately 1 in 5 of all severity and serious injury crashes in the United States and 26 percent of fatal crashes. Annually, this corresponds to 1.2 million all severity, 14,353 serious injury (MAIS 3+), and 7412 fatal crashes. In addition

  14. Fuzzy Neural Network-Based Interacting Multiple Model for Multi-Node Target Tracking Algorithm

    PubMed Central

    Sun, Baoliang; Jiang, Chunlan; Li, Ming

    2016-01-01

    An interacting multiple model for multi-node target tracking algorithm was proposed based on a fuzzy neural network (FNN) to solve the multi-node target tracking problem of wireless sensor networks (WSNs). Measured error variance was adaptively adjusted during the multiple model interacting output stage using the difference between the theoretical and estimated values of the measured error covariance matrix. The FNN fusion system was established during multi-node fusion to integrate with the target state estimated data from different nodes and consequently obtain network target state estimation. The feasibility of the algorithm was verified based on a network of nine detection nodes. Experimental results indicated that the proposed algorithm could trace the maneuvering target effectively under sensor failure and unknown system measurement errors. The proposed algorithm exhibited great practicability in the multi-node target tracking of WSNs. PMID:27809271

  15. Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system.

    PubMed

    Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

    2017-03-13

    The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H + -pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6-81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome.

  16. Polish Experimental Light-Conducting Teletransmission System,

    DTIC Science & Technology

    1982-07-26

    7 AD-AuGB 959 FOREIGN TECHNOLOGY DIV WRIGHT-PATTERSON AFB OH F/G 17/2 PLS EPERIMENTAL LIHT-CONDUCTIN , TELETRANSMTSSION SYSTEM,(U) JUL 82 Z SZPIGLER...amplifier; 1) transmitter; 2) transit amplifier; 3) receiver Transmitting facilities E7] When designing the tract, it was decided that the terminal _- ups...connections between exchanges. The described line has an experimental character. It enables one to collect many valuable data concerning both the design

  17. An Experimental Testbed for Evaluation of Trust and Reputation Systems

    NASA Astrophysics Data System (ADS)

    Kerr, Reid; Cohen, Robin

    To date, trust and reputation systems have often been evaluated using methods of their designers’ own devising. Recently, we demonstrated that a number of noteworthy trust and reputation systems could be readily defeated, revealing limitations in their original evaluations. Efforts in the trust and reputation community to develop a testbed have yielded a successful competition platform, ART. This testbed, however, is less suited to general experimentation and evaluation of individual trust and reputation technologies. In this paper, we propose an experimentation and evaluation testbed based directly on that used in our investigations into security vulnerabilities in trust and reputation systems for marketplaces. We demonstrate the advantages of this design, towards the development of more thorough, objective evaluations of trust and reputation systems.

  18. Design of experimental system for supercritical CO2 fracturing under confining pressure conditions

    NASA Astrophysics Data System (ADS)

    Wang, H.; Lu, Q.; Li, X.; Yang, B.; Zheng, Y.; Shi, L.; Shi, X.

    2018-03-01

    Supercritical CO2 has the characteristics of low viscosity, high diffusion and zero surface tension, and it is considered as a new fluid for non-polluting and non-aqueous fracturing which can be used for shale gas development. Fracturing refers to a method of utilizing the high-pressure fluid to generate fractures in the rock formation so as to improve the oil and gas flow conditions and increase the oil and gas production. In this article, a new type of experimental system for supercritical CO2 fracturing under confining pressure conditions is designed, which is based on characteristics of supercritical CO2, shale reservoir and down-hole environment. The experimental system consists of three sub-systems, including supercritical CO2 generation system, supercritical CO2 fracturing system and data analysis system. It can be used to simulate supercritical CO2 fracturing under geo-stress conditions, thus to study the rock initiation pressure, the formation of the rock fractures, fractured surface morphology and so on. The experimental system has successfully carried out a series of supercritical CO2 fracturing experiments. The experimental results confirm the feasibility of the experimental system and the high efficiency of supercritical CO2 in fracturing tight rocks.

  19. A new EMI system for detection and classification of challenging targets

    NASA Astrophysics Data System (ADS)

    Shubitidze, F.; Fernández, J. P.; Barrowes, B. E.; O'Neill, K.

    2013-06-01

    Advanced electromagnetic induction (EMI) sensors currently feature multi-axis illumination of targets and tri-axial vector sensing (e.g., MetalMapper), or exploit multi-static array data acquisition (e.g., TEMTADS). They produce data of high density, quality, and diversity, and have been combined with advanced EMI models to provide superb classification performance relative to the previous generation of single-axis, monostatic sensors. However, these advances yet have to improve significantly our ability to classify small, deep, and otherwise challenging targets. Particularly, recent live-site discrimination studies at Camp Butner, NC and Camp Beale, CA have revealed that it is more challenging to detect and discriminate small munitions (with calibers ranging from 20 mm to 60 mm) than larger ones. In addition, a live-site test at the Massachusetts Military Reservation, MA highlighted the difficulties for current sensors to classify large, deep, and overlapping targets with high confidence. There are two main approaches to overcome these problems: 1) adapt advanced EMI models to the existing systems and 2) improve the detection limits of current sensors by modifying their hardware. In this paper we demonstrate a combined software/hardware approach that will provide extended detection range and spatial resolution to next-generation EMI systems; we analyze and invert EMI data to extract classification features for small and deep targets; and we propose a new system that features a large transmitter coil.

  20. [Research and application of microcontroller system for target controlled infusion].

    PubMed

    Cheng, Yuke; Dou, Jianhong; Zhang, Xingan; Wang, Ruosong

    2005-08-01

    This paper presents a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extending power and easy manipulation. It has been used in the clinical anesthesia.

  1. Targeting Strategies for the Combination Treatment of Cancer Using Drug Delivery Systems

    PubMed Central

    Kydd, Janel; Jadia, Rahul; Velpurisiva, Praveena; Gad, Aniket; Paliwal, Shailee; Rai, Prakash

    2017-01-01

    Cancer cells have characteristics of acquired and intrinsic resistances to chemotherapy treatment—due to the hostile tumor microenvironment—that create a significant challenge for effective therapeutic regimens. Multidrug resistance, collateral toxicity to normal cells, and detrimental systemic side effects present significant obstacles, necessitating alternative and safer treatment strategies. Traditional administration of chemotherapeutics has demonstrated minimal success due to the non-specificity of action, uptake and rapid clearance by the immune system, and subsequent metabolic alteration and poor tumor penetration. Nanomedicine can provide a more effective approach to targeting cancer by focusing on the vascular, tissue, and cellular characteristics that are unique to solid tumors. Targeted methods of treatment using nanoparticles can decrease the likelihood of resistant clonal populations of cancerous cells. Dual encapsulation of chemotherapeutic drug allows simultaneous targeting of more than one characteristic of the tumor. Several first-generation, non-targeted nanomedicines have received clinical approval starting with Doxil® in 1995. However, more than two decades later, second-generation or targeted nanomedicines have yet to be approved for treatment despite promising results in pre-clinical studies. This review highlights recent studies using targeted nanoparticles for cancer treatment focusing on approaches that target either the tumor vasculature (referred to as ‘vascular targeting’), the tumor microenvironment (‘tissue targeting’) or the individual cancer cells (‘cellular targeting’). Recent studies combining these different targeting methods are also discussed in this review. Finally, this review summarizes some of the reasons for the lack of clinical success in the field of targeted nanomedicines. PMID:29036899

  2. Multiple target laser ablation system

    DOEpatents

    Mashburn, D.N.

    1996-01-09

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film. 3 figs.

  3. Multiple target laser ablation system

    DOEpatents

    Mashburn, Douglas N.

    1996-01-01

    A laser ablation apparatus and method are provided in which multiple targets consisting of material to be ablated are mounted on a movable support. The material transfer rate is determined for each target material, and these rates are stored in a controller. A position detector determines which target material is in a position to be ablated, and then the controller controls the beam trigger timing and energy level to achieve a desired proportion of each constituent material in the resulting film.

  4. Update on B-cell targeted therapies for systemic lupus erythematosus.

    PubMed

    Mok, Chi Chiu

    2014-06-01

    Systemic lupus erythematosus (SLE) is a systemic autoimmune disease characterized by flares and remission, leading to accrual of organ damage over time as a result of persistent tissue inflammation and treatment-related complications. Novel therapies aiming at better treatment response and fewer adverse effects are being tested in the pipeline. This review summarizes the B-cell abnormalities observed in patients with SLE, and updates recent data on the efficacy and safety of B-cell targeted therapies in the treatment of SLE. The pitfalls of clinical trial design and future directions of the development of SLE therapeutics are discussed. The variability of clinical response to treatment in SLE reflects the clinical and immunological heterogeneity of the disease. The treatment plan for patients with SLE should be individualized with the aim of eradicating disease activity, preventing flares and minimizing treatment-related complications. Despite the disappointment of recent clinical trials, B-cell remains the promising target of future SLE therapies. Results from ongoing clinical trials on B-cell targeted biological agents are eagerly awaited.

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

    NASA Astrophysics Data System (ADS)

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

    2008-04-01

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

  6. Targeting the endocannabinoid system to treat anxiety-related disorders.

    PubMed

    Korem, Nachshon; Zer-Aviv, Tomer Mizrachi; Ganon-Elazar, Eti; Abush, Hila; Akirav, Irit

    2016-05-01

    The endocannabinoid system plays an important role in the control of emotions, and its dysregulation has been implicated in several psychiatric disorders. The most common self-reported reason for using cannabis is rooted in its ability to reduce feelings of stress, tension, and anxiety. Nevertheless, there are only few studies in controlled clinical settings that confirm that administration of cannabinoids can benefit patients with a post-traumatic stress disorder (PTSD). There are considerable encouraging preclinical data to suggest that endocannabinoid-targeted therapeutics for anxiety disorders should continue. In this review, we will describe data supporting a role for the endocannabinoid system in preventing and treating anxiety-like behavior in animal models and PTSD patients. Cannabinoids have shown beneficial outcomes in rat and mouse models of anxiety and PTSD, but they also may have untoward effects that discourage their chronic usage, including anxiogenic effects. Hence, clinical and preclinical research on the endocannabinoid system should further study the effects of cannabinoids on anxiety and help determine whether the benefits of using exogenous cannabinoids outweigh the risks. In general, this review suggests that targeting the endocannabinoid system represents an attractive and novel approach to the treatment of anxiety-related disorders and, in particular, PTSD.

  7. Monte Carlo treatment planning for molecular targeted radiotherapy within the MINERVA system

    NASA Astrophysics Data System (ADS)

    Lehmann, Joerg; Hartmann Siantar, Christine; Wessol, Daniel E.; Wemple, Charles A.; Nigg, David; Cogliati, Josh; Daly, Tom; Descalle, Marie-Anne; Flickinger, Terry; Pletcher, David; DeNardo, Gerald

    2005-03-01

    The aim of this project is to extend accurate and patient-specific treatment planning to new treatment modalities, such as molecular targeted radiation therapy, incorporating previously crafted and proven Monte Carlo and deterministic computation methods. A flexible software environment is being created that allows planning radiation treatment for these new modalities and combining different forms of radiation treatment with consideration of biological effects. The system uses common input interfaces, medical image sets for definition of patient geometry and dose reporting protocols. Previously, the Idaho National Engineering and Environmental Laboratory (INEEL), Montana State University (MSU) and Lawrence Livermore National Laboratory (LLNL) had accrued experience in the development and application of Monte Carlo based, three-dimensional, computational dosimetry and treatment planning tools for radiotherapy in several specialized areas. In particular, INEEL and MSU have developed computational dosimetry systems for neutron radiotherapy and neutron capture therapy, while LLNL has developed the PEREGRINE computational system for external beam photon-electron therapy. Building on that experience, the INEEL and MSU are developing the MINERVA (modality inclusive environment for radiotherapeutic variable analysis) software system as a general framework for computational dosimetry and treatment planning for a variety of emerging forms of radiotherapy. In collaboration with this development, LLNL has extended its PEREGRINE code to accommodate internal sources for molecular targeted radiotherapy (MTR), and has interfaced it with the plugin architecture of MINERVA. Results from the extended PEREGRINE code have been compared to published data from other codes, and found to be in general agreement (EGS4—2%, MCNP—10%) (Descalle et al 2003 Cancer Biother. Radiopharm. 18 71-9). The code is currently being benchmarked against experimental data. The interpatient variability of

  8. Microchimeric cells in systemic lupus erythematosus: targets or innocent bystanders?

    PubMed

    Stevens, A M

    2006-01-01

    During pregnancy maternal and fetal cells commute back and forth leading to fetal microchimerism in the mother and maternal microchimerism in the child that can persist for years after the birth. Chimeric fetal and maternal cells can be hematopoietic or can differentiate into somatic cells in multiple organs, potentially acting as targets for 'autoimmunity' and so have been implicated in the pathogenesis of autoimmune diseases that resemble graft-versus-host disease after stem cell transplantation. Fetal cells have been found in women with systemic lupus erythematosus, both in the blood and a target organ, the kidney, suggesting that they may be involved in pathogenesis. Future studies will address how the host immune system normally tolerates maternal and fetal cells or how the balance may change during autoimmunity.

  9. An infrared small target detection method based on multiscale local homogeneity measure

    NASA Astrophysics Data System (ADS)

    Nie, Jinyan; Qu, Shaocheng; Wei, Yantao; Zhang, Liming; Deng, Lizhen

    2018-05-01

    Infrared (IR) small target detection plays an important role in the field of image detection area owing to its intrinsic characteristics. This paper presents a multiscale local homogeneity measure (MLHM) for infrared small target detection, which can enhance the performance of IR small target detection system. Firstly, intra-patch homogeneity of the target itself and the inter-patch heterogeneity between target and the local background regions are integrated to enhance the significant of small target. Secondly, a multiscale measure based on local regions is proposed to obtain the most appropriate response. Finally, an adaptive threshold method is applied to small target segmentation. Experimental results on three different scenarios indicate that the MLHM has good performance under the interference of strong noise.

  10. Effects-based strategy development through center of gravity and target system analysis

    NASA Astrophysics Data System (ADS)

    White, Christopher M.; Prendergast, Michael; Pioch, Nicholas; Jones, Eric K.; Graham, Stephen

    2003-09-01

    This paper describes an approach to effects-based planning in which a strategic-theater-level mission is refined into operational-level and ultimately tactical-level tasks and desired effects, informed by models of the expected enemy response at each level of abstraction. We describe a strategy development system that implements this approach and supports human-in-the-loop development of an effects-based plan. This system consists of plan authoring tools tightly integrated with a suite of center of gravity (COG) and target system analysis tools. A human planner employs the plan authoring tools to develop a hierarchy of tasks and desired effects. Upon invocation, the target system analysis tools use reduced-order models of enemy centers of gravity to select appropriate target set options for the achievement of desired effects, together with associated indicators for each option. The COG analysis tools also provide explicit models of the causal mechanisms linking tasks and desired effects to one another, and suggest appropriate observable indicators to guide ISR planning, execution monitoring, and campaign assessment. We are currently implementing the system described here as part of the AFRL-sponsored Effects Based Operations program.

  11. Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

    DOE PAGES

    Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.; ...

    2017-12-19

    Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

  12. Evolution of Magnetized Liner Inertial Fusion (MagLIF) Targets

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

    Fooks, J. A.; Carlson, L. C.; Fitzsimmons, P.

    Here, the magnetized liner inertial fusion (MagLIF) experimental campaign conducted at the University of Rochester’s Laboratory for Laser Energetics (LLE) has evolved significantly since its start in 2014. Scientific requirements and OMEGA EP system technology both have progressed, resulting in necessary and available updates to the target design. These include, but are not limited to: optimizing target dimensions and aspect ratios to maximize survival at desired pressures; coating target components to enhance physics diagnosis; precision-machining diagnostic windows along the axis of the target; improving fiducial placement reproducibility and reducing subsequent assembly time by 50%; and implementing gas-pressure transducers on themore » targets. In addition, target fabrication techniques have changed and improved, allowing for simpler target reproducibility and decreased assembly time. To date, eleven variations of targets have been fabricated, with successful target fielding ranging from 1 to 20atm internal pressure and a maximum survivability of 33atm.« less

  13. Contribution of self-motion perception to acoustic target localization.

    PubMed

    Pettorossi, V E; Brosch, M; Panichi, R; Botti, F; Grassi, S; Troiani, D

    2005-05-01

    The findings of this study suggest that acoustic spatial perception during head movement is achieved by the vestibular system, which is responsible for the correct dynamic of acoustic target pursuit. The ability to localize sounds in space during whole-body rotation relies on the auditory localization system, which recognizes the position of sound in a head-related frame, and on the sensory systems, namely the vestibular system, which perceive head and body movement. The aim of this study was to analyse the contribution of head motion cues to the spatial representation of acoustic targets in humans. Healthy subjects standing on a rotating platform in the dark were asked to pursue with a laser pointer an acoustic target which was horizontally rotated while the body was kept stationary or maintained stationary while the whole body was rotated. The contribution of head motion to the spatial acoustic representation could be inferred by comparing the gains and phases of the pursuit in the two experimental conditions when the frequency was varied. During acoustic target rotation there was a reduction in the gain and an increase in the phase lag, while during whole-body rotations the gain tended to increase and the phase remained constant. The different contributions of the vestibular and acoustic systems were confirmed by analysing the acoustic pursuit during asymmetric body rotation. In this particular condition, in which self-motion perception gradually diminished, an increasing delay in target pursuit was observed.

  14. Summary: Experimental validation of real-time fault-tolerant systems

    NASA Technical Reports Server (NTRS)

    Iyer, R. K.; Choi, G. S.

    1992-01-01

    Testing and validation of real-time systems is always difficult to perform since neither the error generation process nor the fault propagation problem is easy to comprehend. There is no better substitute to results based on actual measurements and experimentation. Such results are essential for developing a rational basis for evaluation and validation of real-time systems. However, with physical experimentation, controllability and observability are limited to external instrumentation that can be hooked-up to the system under test. And this process is quite a difficult, if not impossible, task for a complex system. Also, to set up such experiments for measurements, physical hardware must exist. On the other hand, a simulation approach allows flexibility that is unequaled by any other existing method for system evaluation. A simulation methodology for system evaluation was successfully developed and implemented and the environment was demonstrated using existing real-time avionic systems. The research was oriented toward evaluating the impact of permanent and transient faults in aircraft control computers. Results were obtained for the Bendix BDX 930 system and Hamilton Standard EEC131 jet engine controller. The studies showed that simulated fault injection is valuable, in the design stage, to evaluate the susceptibility of computing sytems to different types of failures.

  15. Overview of the Neutron experimental facilities at LANSCE

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

    Mocko, Michal

    2016-06-30

    This presentation gives an overview of the neutron experimental facilities at LANSCE. The layout is mentioned in detail, with a map of the south-side experimental facilities, information on Target-4 and the Lujan Center. Then it goes into detail about neutron sources, specifically continuous versus pulsed. Target 4 is then discussed. In conclusion, we have introduced the south-side experimental facilities in operation at LANSCE. 1L target and Target 4 provide complementary neutron energy spectra. Two spallation neutron sources taken together cover more than 11 orders of magnitude in neutron energy.

  16. A Phase l Study of a Tumor-targeted Systemic Nanodelivery System, SGT-94, in Genitourinary Cancers

    PubMed Central

    Siefker-Radtke, Arlene; Zhang, Xin-qiao; Guo, Charles C; Shen, Yu; Pirollo, Kathleen F; Sabir, Sharjeel; Leung, Chris; Leong-Wu, Cindy; Ling, Chi-Ming; Chang, Esther H; Millikan, Randall E; Benedict, William F

    2016-01-01

    Gene therapy development has been limited by our inability to target multifocal cancer with systemic delivery. We developed a systemically administered, tumor-targeted liposomal nanodelivery complex (SGT-94) carrying a plasmid encoding RB94, a truncated form of the RB gene. In preclinical studies, RB94 showed marked cytotoxicity against tumor but not normal cells. SGT-94 was administered intravenously in a first-in-man study in metastatic genitourinary cancer. Minimal side effects were observed; dose-limiting toxicity (DLT) has not been reached in 11 evaluable patients. There was evidence of clinical activity at the 2.4 mg dose with one complete remission (CR) and one partial remission (PR). The patient in CR was retreated upon progression and had a second PR. Furthermore, there was tumor-specific targeting of the SGT-94 complex. One patient had wedge resections of two lung metastases which demonstrated RB94 expression at the DNA level by polymerase chain reaction (PCR) and at the protein level by Western blotting, with no RB94 present in normal contiguous lung. In conclusion, systemically delivered SGT-94 showed evidence of selective tumor targeting and was well tolerated with evidence of clinical activity. Additional studies are warranted to explore the activity of this drug as a single agent and in combination therapy. PMID:27480598

  17. Penalty dynamic programming algorithm for dim targets detection in sensor systems.

    PubMed

    Huang, Dayu; Xue, Anke; Guo, Yunfei

    2012-01-01

    In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations.

  18. Penalty Dynamic Programming Algorithm for Dim Targets Detection in Sensor Systems

    PubMed Central

    Huang, Dayu; Xue, Anke; Guo, Yunfei

    2012-01-01

    In order to detect and track multiple maneuvering dim targets in sensor systems, an improved dynamic programming track-before-detect algorithm (DP-TBD) called penalty DP-TBD (PDP-TBD) is proposed. The performances of tracking techniques are used as a feedback to the detection part. The feedback is constructed by a penalty term in the merit function, and the penalty term is a function of the possible target state estimation, which can be obtained by the tracking methods. With this feedback, the algorithm combines traditional tracking techniques with DP-TBD and it can be applied to simultaneously detect and track maneuvering dim targets. Meanwhile, a reasonable constraint that a sensor measurement can originate from one target or clutter is proposed to minimize track separation. Thus, the algorithm can be used in the multi-target situation with unknown target numbers. The efficiency and advantages of PDP-TBD compared with two existing methods are demonstrated by several simulations. PMID:22666074

  19. Synergistic target combination prediction from curated signaling networks: Machine learning meets systems biology and pharmacology.

    PubMed

    Chua, Huey Eng; Bhowmick, Sourav S; Tucker-Kellogg, Lisa

    2017-10-01

    Given a signaling network, the target combination prediction problem aims to predict efficacious and safe target combinations for combination therapy. State-of-the-art in silico methods use Monte Carlo simulated annealing (mcsa) to modify a candidate solution stochastically, and use the Metropolis criterion to accept or reject the proposed modifications. However, such stochastic modifications ignore the impact of the choice of targets and their activities on the combination's therapeutic effect and off-target effects, which directly affect the solution quality. In this paper, we present mascot, a method that addresses this limitation by leveraging two additional heuristic criteria to minimize off-target effects and achieve synergy for candidate modification. Specifically, off-target effects measure the unintended response of a signaling network to the target combination and is often associated with toxicity. Synergy occurs when a pair of targets exerts effects that are greater than the sum of their individual effects, and is generally a beneficial strategy for maximizing effect while minimizing toxicity. mascot leverages on a machine learning-based target prioritization method which prioritizes potential targets in a given disease-associated network to select more effective targets (better therapeutic effect and/or lower off-target effects); and on Loewe additivity theory from pharmacology which assesses the non-additive effects in a combination drug treatment to select synergistic target activities. Our experimental study on two disease-related signaling networks demonstrates the superiority of mascot in comparison to existing approaches. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The MROI fast tip-tilt correction and target acquisition system

    NASA Astrophysics Data System (ADS)

    Young, John; Buscher, David; Fisher, Martin; Haniff, Christopher; Rea, Alexander; Seneta, Eugene B.; Sun, Xiaowei; Wilson, Donald; Farris, Allen; Olivares, Andres; Selina, Robert

    2012-07-01

    The fast tip-tilt correction system for the Magdalena Ridge Observatory Interferometer (MROI) is being designed and fabricated by the University of Cambridge. The design of the system is currently at an advanced stage and the performance of its critical subsystems has been verified in the laboratory. The system has been designed to meet a demanding set of specifications including satisfying all performance requirements in ambient temperatures down to -5 °C, maintaining the stability of the tip-tilt fiducial over a 5 °C temperature change without recourse to an optical reference, and a target acquisition mode with a 60” field-of-view. We describe the important technical features of the system, which uses an Andor electron-multiplying CCD camera protected by a thermal enclosure, a transmissive optical system with mounts incorporating passive thermal compensation, and custom control software running under Xenomai real-time Linux. We also report results from laboratory tests that demonstrate (a) the high stability of the custom optic mounts and (b) the low readout and compute latencies that will allow us to achieve a 40 Hz closed-loop bandwidth on bright targets.

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

    PubMed Central

    2011-01-01

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

  2. Design and Experimental Study of an Over-Under TBCC Exhaust System.

    PubMed

    Mo, Jianwei; Xu, Jinglei; Zhang, Liuhuan

    2014-01-01

    Turbine-based combined-cycle (TBCC) propulsion systems have been a topic of research as a means for more efficient flight at supersonic and hypersonic speeds. The present study focuses on the fundamental physics of the complex flow in the TBCC exhaust system during the transition mode as the turbine exhaust is shut off and the ramjet exhaust is increased. A TBCC exhaust system was designed using methods of characteristics (MOC) and subjected to experimental and computational study. The main objectives of the study were: (1) to identify the interactions between the two exhaust jet streams during the transition mode phase and their effects on the whole flow-field structure; (2) to determine and verify the aerodynamic performance of the over-under TBCC exhaust nozzle; and (3) to validate the simulation ability of the computational fluid dynamics (CFD) software according to the experimental conditions. Static pressure taps and Schlieren apparatus were employed to obtain the wall pressure distributions and flow-field structures. Steady-state tests were performed with the ramjet nozzle cowl at six different positions at which the turbine flow path were half closed and fully opened, respectively. Methods of CFD were used to simulate the exhaust flow and they complemented the experimental study by providing greater insight into the details of the flow field and a means of verifying the experimental results. Results indicated that the flow structure was complicated because the two exhaust jet streams interacted with each other during the exhaust system mode transition. The exhaust system thrust coefficient varied from 0.9288 to 0.9657 during the process. The CFD simulation results agree well with the experimental data, which demonstrated that the CFD methods were effective in evaluating the aerodynamic performance of the TBCC exhaust system during the mode transition.

  3. Application of the marine Ex-Bz transient system for delineating near shore resistive targets

    NASA Astrophysics Data System (ADS)

    Levi, Eldad; Goldman, Mark

    2017-09-01

    Under certain conditions, multidimensional coastal effect significantly enhances relative target response of the broadside transient marine Ex-Bz system. The effect is caused by a redistribution of the induced currents between the resistive target and the sea bottom compared to that existing in a 1-D geometry. As a result, the effect strongly depends on specific geoelectric conditions in the near-shore environment. The first study of the effect in the Mediterranean coast of central Israel was addressing shallow groundwater problem under specific geoelectric, hydrogeological and geomorphological conditions. Under different conditions (e.g. deep targets and sharp near-shore bathymetry), the influence of the effect on target response might be significantly different. More general analysis carried out in this study comprises various geoelectric scenarios that include both shallow and deep resistive targets at different distances from the shore line as well as various geometries of the target and the near-shore bathymetry. The study includes three major exploration aspects of the system, namely signal detectability, lateral and vertical resolution. Taking into account poor lateral resolution of the classical frequency domain CSEM and the limited application in shallow sea, the described broadside transient Ex-Bz system might represent a desired alternative for delineating shallow and deep resistive targets in transition zone.

  4. Targeted mutagenesis in cotton (Gossypium hirsutum L.) using the CRISPR/Cas9 system

    PubMed Central

    Chen, Xiugui; Lu, Xuke; Shu, Na; Wang, Shuai; Wang, Junjuan; Wang, Delong; Guo, Lixue; Ye, Wuwei

    2017-01-01

    The CRISPR (Clustered Regularly Interspaced Short Palindromic Repeats)/Cas9 system has been widely used for genome editing in various plants because of its simplicity, high efficiency and design flexibility. However, to our knowledge, there is no report on the application of CRISPR/Cas9-mediated targeted mutagenesis in cotton. Here, we report the genome editing and targeted mutagenesis in upland cotton (Gossypium hirsutum L., hereafter cotton) using the CRISPR/Cas9 system. We designed two guide RNAs to target distinct sites of the cotton Cloroplastos alterados 1 (GhCLA1) and vacuolar H+-pyrophosphatase (GhVP) genes. Mutations in these two genes were detected in cotton protoplasts. Most of the mutations were nucleotide substitutions, with one nucleotide insertion and one substitution found in GhCLA1 and one deletion found in GhVP in cotton protoplasts. Subsequently, the two vectors were transformed into cotton shoot apexes through Agrobacterium-mediated transformation, resulting in efficient target gene editing. Most of the mutations were nucleotide deletions, and the mutation efficiencies were 47.6–81.8% in transgenic cotton plants. Evaluation using restriction-enzyme-PCR assay and sequence analysis detected no off-target mutations. Our results indicated that the CRISPR/Cas9 system was an efficient and specific tool for targeted mutagenesis of the cotton genome. PMID:28287154

  5. Local and Systemic Inflammatory Responses to Experimentally Induced Gingivitis

    PubMed Central

    Leishman, Shaneen J.; Seymour, Gregory J.; Ford, Pauline J.

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual. PMID:24227893

  6. Local and systemic inflammatory responses to experimentally induced gingivitis.

    PubMed

    Leishman, Shaneen J; Seymour, Gregory J; Ford, Pauline J

    2013-01-01

    This study profiled the local and systemic inflammatory responses to experimentally induced gingivitis. Eight females participated in a 21-day experimental gingivitis model followed by a 14-day resolution phase. Bleeding on probing and plaque index scores were assessed before, during, and after resolution of gingival inflammation, and samples of saliva, GCF, and plasma were collected. Samples were assessed for biomarkers of inflammation using the BioPlex platform and ELISA. There were no significant changes in GCF levels of cytokines during the experimental phase; however, individual variability in cytokine profiles was noted. During resolution, mean GCF levels of IL-2, IL-6, and TNF-α decreased and were significantly lower than baseline levels (P = 0.003, P = 0.025, and P = 0.007, resp.). Furthermore, changes in GCF levels of IL-2, IL-6, and TNF-α during resolution correlated with changes in plaque index scores (r = 0.88, P = 0.004; r = 0.72, P = 0.042; r = 0.79, P = 0.019, resp.). Plasma levels of sICAM-1 increased significantly during the experimental phase (P = 0.002) and remained elevated and significantly higher than baseline levels during resolution (P < 0.001). These results support the concept that gingivitis adds to the systemic inflammatory burden of an individual.

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

    PubMed

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

    2017-01-01

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

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

    PubMed Central

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

    2017-01-01

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

  9. New experimental model for single liver lobe hyperthermia in small animals using non-directional microwaves

    PubMed Central

    Iliescu, Radu; Dimofte, Gabriel M.

    2017-01-01

    Purpose Our aim was to develop a new experimental model for in vivo hyperthermia using non-directional microwaves, applicable to small experimental animals. We present an affordable approach for targeted microwave heat delivery to an isolated liver lobe in rat, which allows rapid, precise and stable tissue temperature control. Materials and methods A new experimental model is proposed. We used a commercial available magnetron generating 2450 MHz, with 4.4V and 14A in the filament and 4500V anodic voltage. Modifications were required in order to adjust tissue heating such as to prevent overheating and to allow for fine adjustments according to real-time target temperature. The heating is controlled using a virtual instrument application implemented in LabView® and responds to 0.1° C variations in the target. Ten healthy adult male Wistar rats, weighing 250–270 g were used in this study. The middle liver lobe was the target for controlled heating, while the rest of the living animal was protected. Results In vivo microwave delivery using our experimental setting is safe for the animals. Target tissue temperature rises from 30°C to 40°C with 3.375°C / second (R2 = 0.9551), while the increment is lower it the next two intervals (40–42°C and 42–44°C) with 0.291°C/ s (R2 = 0.9337) and 0.136°C/ s (R2 = 0.7894) respectively, when testing in sequences. After reaching the desired temperature, controlled microwave delivery insures a very stable temperature during the experiments. Conclusions We have developed an inexpensive and easy to manufacture system for targeted hyperthermia using non-directional microwave radiation. This system allows for fine and stable temperature adjustments within the target tissue and is ideal for experimental models testing below or above threshold hyperthermia PMID:28934251

  10. A time-of-flight system for the external target facility

    NASA Astrophysics Data System (ADS)

    Zhang, Xue-Heng; Yu, Yu-Hong; Sun, Zhi-Yu; Mao, Rui-Shi; Wang, Shi-Tao; Zhou, Yong; Yan, Duo; Liu, Long-Xiang

    2013-05-01

    A time-of-flight system with a plastic scintillator coupled to photomultipliers is developed for the external target facility (ETF). This system can satisfy the requirement of an ultrahigh vacuum (~10-9 mbar), a high counting rate (~106 particles per second) and a magnetic field environment. In the beam test experiment, a total time resolution of 580 ps FWHM was obtained for the whole system, and nuclei with a mass of up to 80 could be identified using this system.

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

    NASA Technical Reports Server (NTRS)

    Sugumaran, Vijayan; Gomaa, Hassan; Kerschberg, Larry

    1991-01-01

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

  12. Interacting with target tracking algorithms in a gaze-enhanced motion video analysis system

    NASA Astrophysics Data System (ADS)

    Hild, Jutta; Krüger, Wolfgang; Heinze, Norbert; Peinsipp-Byma, Elisabeth; Beyerer, Jürgen

    2016-05-01

    Motion video analysis is a challenging task, particularly if real-time analysis is required. It is therefore an important issue how to provide suitable assistance for the human operator. Given that the use of customized video analysis systems is more and more established, one supporting measure is to provide system functions which perform subtasks of the analysis. Recent progress in the development of automated image exploitation algorithms allow, e.g., real-time moving target tracking. Another supporting measure is to provide a user interface which strives to reduce the perceptual, cognitive and motor load of the human operator for example by incorporating the operator's visual focus of attention. A gaze-enhanced user interface is able to help here. This work extends prior work on automated target recognition, segmentation, and tracking algorithms as well as about the benefits of a gaze-enhanced user interface for interaction with moving targets. We also propose a prototypical system design aiming to combine both the qualities of the human observer's perception and the automated algorithms in order to improve the overall performance of a real-time video analysis system. In this contribution, we address two novel issues analyzing gaze-based interaction with target tracking algorithms. The first issue extends the gaze-based triggering of a target tracking process, e.g., investigating how to best relaunch in the case of track loss. The second issue addresses the initialization of tracking algorithms without motion segmentation where the operator has to provide the system with the object's image region in order to start the tracking algorithm.

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

    PubMed

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

    2018-01-19

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

  14. Computer-based prediction of mitochondria-targeting peptides.

    PubMed

    Martelli, Pier Luigi; Savojardo, Castrense; Fariselli, Piero; Tasco, Gianluca; Casadio, Rita

    2015-01-01

    Computational methods are invaluable when protein sequences, directly derived from genomic data, need functional and structural annotation. Subcellular localization is a feature necessary for understanding the protein role and the compartment where the mature protein is active and very difficult to characterize experimentally. Mitochondrial proteins encoded on the cytosolic ribosomes carry specific patterns in the precursor sequence from where it is possible to recognize a peptide targeting the protein to its final destination. Here we discuss to which extent it is feasible to develop computational methods for detecting mitochondrial targeting peptides in the precursor sequences and benchmark our and other methods on the human mitochondrial proteins endowed with experimentally characterized targeting peptides. Furthermore, we illustrate our newly implemented web server and its usage on the whole human proteome in order to infer mitochondrial targeting peptides, their cleavage sites, and whether the targeting peptide regions contain or not arginine-rich recurrent motifs. By this, we add some other 2,800 human proteins to the 124 ones already experimentally annotated with a mitochondrial targeting peptide.

  15. Molecular Composition Analysis of Distant Targets

    NASA Technical Reports Server (NTRS)

    Hughes, Gary B.; Lubin, Philip

    2017-01-01

    This document is the Final Report for NASA Innovative Advanced Concepts (NIAC) Phase I Grant 15-NIAC16A-0145, titled Molecular Composition Analysis of Distant Targets. The research was focused on developing a system concept for probing the molecular composition of cold solar system targets, such as Asteroids, Comets, Planets and Moons from a distant vantage, for example from a spacecraft that is orbiting the target (Hughes et al., 2015). The orbiting spacecraft is equipped with a high-power laser, which is run by electricity from photovoltaic panels. The laser is directed at a spot on the target. Materials on the surface of the target are heated by the laser beam, and begin to melt and then evaporate, forming a plume of asteroid molecules in front of the heated spot. The heated spot glows, producing blackbody illumination that is visible from the spacecraft, via a path through the evaporated plume. As the blackbody radiation from the heated spot passes through the plume of evaporated material, molecules in the plume absorb radiation in a manner that is specific to the rotational and vibrational characteristics of the specific molecules. A spectrometer aboard the spacecraft is used to observe absorption lines in the blackbody signal. The pattern of absorption can be used to estimate the molecular composition of materials in the plume, which originated on the target. Focusing on a single spot produces a borehole, and shallow subsurface profiling of the targets bulk composition is possible. At the beginning of the Phase I research, the estimated Technology Readiness Level (TRL) of the system was TRL-1. During the Phase I research, an end-to-end theoretical model of the sensor system was developed from first principles. The model includes laser energy and optical propagation, target heating, melting and evaporation of target material, plume density, thermal radiation from the heated spot, molecular cross section of likely asteroid materials, and estimation of the

  16. Nonlinear System Identification for Aeroelastic Systems with Application to Experimental Data

    NASA Technical Reports Server (NTRS)

    Kukreja, Sunil L.

    2008-01-01

    Representation and identification of a nonlinear aeroelastic pitch-plunge system as a model of the Nonlinear AutoRegressive, Moving Average eXogenous (NARMAX) class is considered. A nonlinear difference equation describing this aircraft model is derived theoretically and shown to be of the NARMAX form. Identification methods for NARMAX models are applied to aeroelastic dynamics and its properties demonstrated via continuous-time simulations of experimental conditions. Simulation results show that (1) the outputs of the NARMAX model closely match those generated using continuous-time methods, and (2) NARMAX identification methods applied to aeroelastic dynamics provide accurate discrete-time parameter estimates. Application of NARMAX identification to experimental pitch-plunge dynamics data gives a high percent fit for cross-validated data.

  17. Distributed Peer-to-Peer Target Tracking in Wireless Sensor Networks

    PubMed Central

    Wang, Xue; Wang, Sheng; Bi, Dao-Wei; Ma, Jun-Jie

    2007-01-01

    Target tracking is usually a challenging application for wireless sensor networks (WSNs) because it is always computation-intensive and requires real-time processing. This paper proposes a practical target tracking system based on the auto regressive moving average (ARMA) model in a distributed peer-to-peer (P2P) signal processing framework. In the proposed framework, wireless sensor nodes act as peers that perform target detection, feature extraction, classification and tracking, whereas target localization requires the collaboration between wireless sensor nodes for improving the accuracy and robustness. For carrying out target tracking under the constraints imposed by the limited capabilities of the wireless sensor nodes, some practically feasible algorithms, such as the ARMA model and the 2-D integer lifting wavelet transform, are adopted in single wireless sensor nodes due to their outstanding performance and light computational burden. Furthermore, a progressive multi-view localization algorithm is proposed in distributed P2P signal processing framework considering the tradeoff between the accuracy and energy consumption. Finally, a real world target tracking experiment is illustrated. Results from experimental implementations have demonstrated that the proposed target tracking system based on a distributed P2P signal processing framework can make efficient use of scarce energy and communication resources and achieve target tracking successfully.

  18. SU-F-T-211: Evaluation of a Dual Focusing Magnet System for the Treatment of Small Proton Targets

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

    Nguyen, TT; McAuley, GA; Heczko, S

    Purpose: To investigate magnetic focusing for small volume proton targets using a doublet combination of quadrupole rare earth permanent magnet Halbach cylinder assemblies Methods: Monte Carlo computer simulations were performed using the Geant4 toolkit to compare dose depositions of proton beams transported through two focusing magnets or in their absence. Proton beams with energies of 127 MeV and initial diameters of 5, 8 and 10 mm were delivered through two identical focusing magnets similar to those currently in experimental use at Loma Linda University Medical Center. Analogous experiments used optimized configurations based on the simulation results. Dose was measured bymore » a diode detector and Gafchromic EBT3 film and compared to simulation data. Based on results from the experimental data, an additional set of simulations was performed with an initial beam diameter of 18 mm and a two differing length magnets (40mm & 68mm). Results: Experimental data matched well with Monte Carlo simulations. However, under conditions necessary to produce circular beam spots at target depth, magnetically focused beams using two identical 40 mm length magnets did not meet all of our performance criteria of circular beam spots, improved peak to entrance (P/E) dose ratios and dose delivery efficiencies. The simulations using the longer 68 mm 2nd magnet yielded better results with 34% better P/E dose ratio and 20–50% better dose delivery efficiencies when compared to unfocused 10 mm beams. Conclusion: While magnetic focusing using two magnets with identical focusing power did not yield desired results, ongoing Monte Carlo simulations suggest that increasing the length of the 2nd magnet to 68 mm could improve P/E dose ratios and dose efficiencies. Future work includes additional experimental validation of the longer 2nd magnet setup as well as experiments with triplet magnet systems. This project was sponsored with funding from the Department of Defense (DOD# W81XWH-BAA-10

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

    NASA Astrophysics Data System (ADS)

    Kansky, Jan E.; Murphy, Daniel V.

    2007-09-01

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

  20. Experimental verification of an interpolation algorithm for improved estimates of animal position

    NASA Astrophysics Data System (ADS)

    Schell, Chad; Jaffe, Jules S.

    2004-07-01

    This article presents experimental verification of an interpolation algorithm that was previously proposed in Jaffe [J. Acoust. Soc. Am. 105, 3168-3175 (1999)]. The goal of the algorithm is to improve estimates of both target position and target strength by minimizing a least-squares residual between noise-corrupted target measurement data and the output of a model of the sonar's amplitude response to a target at a set of known locations. Although this positional estimator was shown to be a maximum likelihood estimator, in principle, experimental verification was desired because of interest in understanding its true performance. Here, the accuracy of the algorithm is investigated by analyzing the correspondence between a target's true position and the algorithm's estimate. True target position was measured by precise translation of a small test target (bead) or from the analysis of images of fish from a coregistered optical imaging system. Results with the stationary spherical test bead in a high signal-to-noise environment indicate that a large increase in resolution is possible, while results with commercial aquarium fish indicate a smaller increase is obtainable. However, in both experiments the algorithm provides improved estimates of target position over those obtained by simply accepting the angular positions of the sonar beam with maximum output as target position. In addition, increased accuracy in target strength estimation is possible by considering the effects of the sonar beam patterns relative to the interpolated position. A benefit of the algorithm is that it can be applied ``ex post facto'' to existing data sets from commercial multibeam sonar systems when only the beam intensities have been stored after suitable calibration.

  1. Simple Monitoring of Gene Targeting Efficiency in Human Somatic Cell Lines Using the PIGA Gene

    PubMed Central

    Karnan, Sivasundaram; Konishi, Yuko; Ota, Akinobu; Takahashi, Miyuki; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

    2012-01-01

    Gene targeting in most of human somatic cell lines has been labor-intensive because of low homologous recombination efficiency. The development of an experimental system that permits a facile evaluation of gene targeting efficiency in human somatic cell lines is the first step towards the improvement of this technology and its application to a broad range of cell lines. In this study, we utilized phosphatidylinositol glycan anchor biosynthesis class A (PIGA), a gene essential for the synthesis of glycosylphosphatidyl inositol (GPI) anchors, as a reporter of gene targeting events in human somatic cell lines. Targeted disruption of PIGA was quantitatively detected with FLAER, a reagent that specifically binds to GPI anchors. Using this PIGA-based reporter system, we successfully detected adeno-associated virus (AAV)-mediated gene targeting events both with and without promoter-trap enrichment of gene-targeted cell population. The PIGA-based reporter system was also capable of reproducing previous findings that an AAV-mediated gene targeting achieves a remarkably higher ratio of homologous versus random integration (H/R ratio) of targeting vectors than a plasmid-mediated gene targeting. The PIGA-based system also detected an approximately 2-fold increase in the H/R ratio achieved by a small negative selection cassette introduced at the end of the AAV-based targeting vector with a promoter-trap system. Thus, our PIGA-based system is useful for monitoring AAV-mediated gene targeting and will assist in improving gene targeting technology in human somatic cell lines. PMID:23056640

  2. Chromosomal targeting by CRISPR-Cas systems can contribute to genome plasticity in bacteria

    PubMed Central

    Dy, Ron L; Pitman, Andrew R; Fineran, Peter C

    2013-01-01

    The clustered regularly interspaced short palindromic repeats (CRISPR) and their associated (Cas) proteins form adaptive immune systems in bacteria to combat phage and other foreign genetic elements. Typically, short spacer sequences are acquired from the invader DNA and incorporated into CRISPR arrays in the bacterial genome. Small RNAs are generated that contain these spacer sequences and enable sequence-specific destruction of the foreign nucleic acids. Occasionally, spacers are acquired from the chromosome, which instead leads to targeting of the host genome. Chromosomal targeting is highly toxic to the bacterium, providing a strong selective pressure for a variety of evolutionary routes that enable host cell survival. Mutations that inactivate the CRISPR-Cas functionality, such as within the cas genes, CRISPR repeat, protospacer adjacent motifs (PAM), and target sequence, mediate escape from toxicity. This self-targeting might provide some explanation for the incomplete distribution of CRISPR-Cas systems in less than half of sequenced bacterial genomes. More importantly, self-genome targeting can cause large-scale genomic alterations, including remodeling or deletion of pathogenicity islands and other non-mobile chromosomal regions. While control of horizontal gene transfer is perceived as their main function, our recent work illuminates an alternative role of CRISPR-Cas systems in causing host genomic changes and influencing bacterial evolution. PMID:24251073

  3. Experimental land observing data system feasibility study

    NASA Technical Reports Server (NTRS)

    Buckley, J. L.; Kraiman, H.

    1982-01-01

    An end-to-end data system to support a Shuttle-based Multispectral Linear Array (MLA) mission in the mid-1980's was defined. The experimental Land Observing System (ELOS) is discussed. A ground system that exploits extensive assets from the LANDSAT-D Program to effectively meet the objectives of the ELOS Mission was defined. The goal of 10 meter pixel precision, the variety of data acquisition capabilities, and the use of Shuttle are key to the mission requirements, Ground mission management functions are met through the use of GSFC's Multi-Satellite Operations Control Center (MSOCC). The MLA Image Generation Facility (MIGF) combines major hardware elements from the Applications Development Data System (ADDS) facility and LANDSAT Assessment System (LAS) with a special purpose MLA interface unit. LANDSAT-D image processing techniques, adapted to MLA characteristics, form the basis for the use of existing software and the definition of new software required.

  4. Personality trait inferences of Turkish immigrant and neutral targets: an experimental study.

    PubMed

    Sandal, Gro M; Bye, Hege H; Pallesen, Ståle

    2012-12-01

    The study investigated whether personality traits attributed to immigrant targets differ from personality inferences made for a neutral target, and whether trait attributions differ for assimilated and integrated immigrant targets. Participants (n = 340) were randomized to one of three conditions in which they read the same story about a person, but where the person was described as either: (a) an assimilated Turkish immigrant; (b) an integrated Turkish immigrant; or (c) neutral (no nationality or religious practice indicated). Subsequently, they rated the personality of the described person on the NEO-Five Factor Inventory (observer rating version) and completed the Balanced Inventory of Desirable Responding (Impression Management scale) with reference to themselves. Both immigrant targets were rated as significantly higher on extraversion and lower on neuroticism than the neutral target. The integrated target was rated as more open than the neutral target, and as higher than the assimilated target on neuroticism when controlling for impression management. © 2012 The Authors. Scandinavian Journal of Psychology © 2012 The Scandinavian Psychological Associations.

  5. The skeletal endocannabinoid system: clinical and experimental insights.

    PubMed

    Raphael, Bitya; Gabet, Yankel

    2016-05-01

    Recently, there has been a rapidly growing interest in the role of cannabinoids in the regulation of skeletal remodeling and bone mass, addressed in basic, translational and clinical research. Since the first publications in 2005, there are more than 1000 publications addressing the skeletal endocannabinoid system. This review focuses on the roles of the endocannabinoid system in skeletal biology via the cannabinoid receptors CB1, CB2 and others. Endocannabinoids play important roles in bone formation, bone resorption and skeletal growth, and are sometimes age, gender, species and strain dependent. Controversies in the literature and potential therapeutic approaches targeting the endocannabinoid system in skeletal disorders are also discussed.

  6. The Johnson Space Center Experimental Impact Lab: Contributions Toward Understanding the Evolution of the Solar System

    NASA Technical Reports Server (NTRS)

    See, T. H.; Montes, R.

    2012-01-01

    Impact is the most common and only weathering phenomenon affecting all the planetary bodies (e.g., planets, satellites, asteroids, comets, etc.) in the solar system. NASA Johnson Space Center s Experimental Impact Laboratory (EIL) includes three accelerators that are used in support of research into the effects of impact on the formation and evolution of the solar system. They permit researchers to study a wide variety of phenomena associated with high-velocity impacts into a wide range of geologic targets and materials relevant to astrobiological studies. By studying these processes, researchers can investigate the histories and evolution of planetary bodies and the solar system as a whole. While the majority of research conducted in the EIL addresses questions involving planetary impacts, work involving spacecraft components has been performed on occasion. An example of this is the aerogel collector material flown on the Stardust spacecraft that traveled to Comet Wild-2. This capture medium was tested and flight qualified using the 5 mm Light-Gas Gun located in the EIL.

  7. Systems Pharmacology-Based Discovery of Natural Products for Precision Oncology Through Targeting Cancer Mutated Genes.

    PubMed

    Fang, J; Cai, C; Wang, Q; Lin, P; Zhao, Z; Cheng, F

    2017-03-01

    Massive cancer genomics data have facilitated the rapid revolution of a novel oncology drug discovery paradigm through targeting clinically relevant driver genes or mutations for the development of precision oncology. Natural products with polypharmacological profiles have been demonstrated as promising agents for the development of novel cancer therapies. In this study, we developed an integrated systems pharmacology framework that facilitated identifying potential natural products that target mutated genes across 15 cancer types or subtypes in the realm of precision medicine. High performance was achieved for our systems pharmacology framework. In case studies, we computationally identified novel anticancer indications for several US Food and Drug Administration-approved or clinically investigational natural products (e.g., resveratrol, quercetin, genistein, and fisetin) through targeting significantly mutated genes in multiple cancer types. In summary, this study provides a powerful tool for the development of molecularly targeted cancer therapies through targeting the clinically actionable alterations by exploiting the systems pharmacology of natural products. © 2017 The Authors CPT: Pharmacometrics & Systems Pharmacology published by Wiley Periodicals, Inc. on behalf of American Society for Clinical Pharmacology and Therapeutics.

  8. Experimentally studied dynamic dose interplay does not meaningfully affect target dose in VMAT SBRT lung treatments.

    PubMed

    Stambaugh, Cassandra; Nelms, Benjamin E; Dilling, Thomas; Stevens, Craig; Latifi, Kujtim; Zhang, Geoffrey; Moros, Eduardo; Feygelman, Vladimir

    2013-09-01

    The effects of respiratory motion on the tumor dose can be divided into the gradient and interplay effects. While the interplay effect is likely to average out over a large number of fractions, it may play a role in hypofractionated [stereotactic body radiation therapy (SBRT)] treatments. This subject has been extensively studied for intensity modulated radiation therapy but less so for volumetric modulated arc therapy (VMAT), particularly in application to hypofractionated regimens. Also, no experimental study has provided full four-dimensional (4D) dose reconstruction in this scenario. The authors demonstrate how a recently described motion perturbation method, with full 4D dose reconstruction, is applied to describe the gradient and interplay effects during VMAT lung SBRT treatments. VMAT dose delivered to a moving target in a patient can be reconstructed by applying perturbations to the treatment planning system-calculated static 3D dose. Ten SBRT patients treated with 6 MV VMAT beams in five fractions were selected. The target motion (motion kernel) was approximated by 3D rigid body translation, with the tumor centroids defined on the ten phases of the 4DCT. The motion was assumed to be periodic, with the period T being an average from the empirical 4DCT respiratory trace. The real observed tumor motion (total displacement ≤ 8 mm) was evaluated first. Then, the motion range was artificially increased to 2 or 3 cm. Finally, T was increased to 60 s. While not realistic, making T comparable to the delivery time elucidates if the interplay effect can be observed. For a single fraction, the authors quantified the interplay effect as the maximum difference in the target dosimetric indices, most importantly the near-minimum dose (D99%), between all possible starting phases. For the three- and five-fractions, statistical simulations were performed when substantial interplay was found. For the motion amplitudes and periods obtained from the 4DCT, the interplay effect

  9. Targeting bacterial secretion systems: benefits of disarmament in the microcosm.

    PubMed

    Baron, Christian; Coombes, Brian

    2007-03-01

    Secretion systems are used by many bacterial pathogens for the delivery of virulence factors to the extracellular space or directly into host cells. They are attractive targets for the development of novel anti-virulence drugs as their inactivation would lead to pathogen attenuation or avirulence, followed by clearance of the bacteria by the immune system. This review will present the state of knowledge on the assembly and function of type II, type III and type IV secretion systems in Gram-negative bacteria focusing on insights provided by structural analyses of several key components. The suitability of transcription factors regulating the expression of secretion system components and of ATPases, lytic transglycosylases and protein assembly factors as drug targets will be discussed. Recent progress using innovative in vivo as well as in vitro screening strategies led to a first set of secretion system inhibitors with potential for further development as anti-infectives. The discovery of such inhibitors offers exciting and innovative opportunities to further develop these anti-virulence drugs into monotherapy or in combination with classical antibiotics. Bacterial growth per se would not be inhibited by such drugs so that the selection for mutations causing resistance could be reduced. Secretion system inhibitors may therefore avoid many of the problems associated with classical antibiotics and may constitute a valuable addition to our arsenal for the treatment of bacterial infections.

  10. Optical system design of solar-blind UV target simulator with long focal length

    NASA Astrophysics Data System (ADS)

    Chen, Yu; Huo, Furong; Zheng, Liqin

    2014-11-01

    Ultraviolet (UV) radiation of 200nm-300nm waveband from the sun is absorbed by atmosphere, which is often referred to the solar-blind region of the solar spectrum. Solar-blind characteristics of this waveband have important application value, especially in military fields. The application of solar-blind waveband has developed very rapidly, which is receiving more and more attention. Sometimes, to test the performance of a UV optical system, a standard solar-blind UV target simulator is needed as the UV light source. In this paper, an optical system of a solar-blind UV target simulator is designed with waveband 240nm-280nm. To simulate a far UV target, the focal length of this UV optical system needs to be long. Besides, different field of view (FOV) of the system should meet aplanatic condition. The optional materials are very few for UV optical systems, in which only CaF2 and JGS1 are commonly used. Various aberrations are difficult to be corrected. To save production cost and enhance the precision of fabrication and test, aspheric surfaces and binary elements are not adopted in the system. Moreover, doublet or triplet cannot be used in UV optical system considering possible cracking for different thermal expansion coefficients of different materials. After optimization, the system is composed of 4 lenses with focal length 500mm. MTF curves of different FOV coincide together. The maximum RMS radius of the optimized system has almost the same size as Airy disk, which proves the good image quality after system optimization. The aplanatic condition is met very well in this system. In the spot diagram, root mean square (RMS) radius changes from 3 microns to 3.6 microns, which has similar size with Airy disk and meets aplanatic condition very well. This optical system of solar-blind UV target simulator also has relatively loose tolerance data, which can prove the system is designed in an optimal state.

  11. Environmental Management System Objectives & Targets Results Summary - FY 2015.

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

    Vetter, Douglas W.

    2016-02-01

    Sandia National Laboratories (SNL) Environmental Management System is the integrated approach for members of the workforce to identify and manage environmental risks. Each Fiscal Year (FY) SNL performs an analysis to identify environmental aspects, and the environmental programs associated with them are charged with the task of routinely monitoring and measuring the objectives and targets that are established to mitigate potential impacts of SNL's operations on the environment. An annual summary of the results achieved towards meeting established Sandia Corporation and SNL Site-specific objectives and targets provides a connection to, and rational for, annually revised environmental aspects. The purpose ofmore » this document is to summarize the results achieved and documented in FY 2015.« less

  12. A novel infrared small moving target detection method based on tracking interest points under complicated background

    NASA Astrophysics Data System (ADS)

    Dong, Xiabin; Huang, Xinsheng; Zheng, Yongbin; Bai, Shengjian; Xu, Wanying

    2014-07-01

    Infrared moving target detection is an important part of infrared technology. We introduce a novel infrared small moving target detection method based on tracking interest points under complicated background. Firstly, Difference of Gaussians (DOG) filters are used to detect a group of interest points (including the moving targets). Secondly, a sort of small targets tracking method inspired by Human Visual System (HVS) is used to track these interest points for several frames, and then the correlations between interest points in the first frame and the last frame are obtained. Last, a new clustering method named as R-means is proposed to divide these interest points into two groups according to the correlations, one is target points and another is background points. In experimental results, the target-to-clutter ratio (TCR) and the receiver operating characteristics (ROC) curves are computed experimentally to compare the performances of the proposed method and other five sophisticated methods. From the results, the proposed method shows a better discrimination of targets and clutters and has a lower false alarm rate than the existing moving target detection methods.

  13. An experimental system for coiled tubing partial underbalanced drilling (CT-PUBD) technique

    NASA Astrophysics Data System (ADS)

    Shi, H. Z.; Ji, Z. S.; Zhao, H. Q.; Chen, Z. L.; Zhang, H. Z.

    2018-05-01

    To improve the rate of penetration (ROP) in hard formations, a new high-speed drilling technique called Coiled Tubing Partial Underbalanced Drilling (CT-PUBD) is proposed. This method uses a rotary packer to realize an underbalanced condition near the bit by creating a micro-annulus and an overbalanced condition at the main part of the annulus. A new full-scale laboratory experimental system is designed and set up to study the hydraulic characteristics and drilling performance of this method. The system is composed of a drilling system, circulation system, and monitor system, including three key devices, namely, cuttings discharge device, rotary packer, and backflow device. The experimental results showed that the pressure loss increased linearly with the flow rate of the drilling fluid. The high drilling speed of CT-PUBD proved it a better drilling method than the conventional drilling. The experimental system may provide a fundamental basis for the research of CT-PUBD, and the results proved that this new method is feasible in enhancing ROP and guaranteeing the drilling safety.

  14. Fuzzy System-Based Target Selection for a NIR Camera-Based Gaze Tracker

    PubMed Central

    Naqvi, Rizwan Ali; Arsalan, Muhammad; Park, Kang Ryoung

    2017-01-01

    Gaze-based interaction (GBI) techniques have been a popular subject of research in the last few decades. Among other applications, GBI can be used by persons with disabilities to perform everyday tasks, as a game interface, and can play a pivotal role in the human computer interface (HCI) field. While gaze tracking systems have shown high accuracy in GBI, detecting a user’s gaze for target selection is a challenging problem that needs to be considered while using a gaze detection system. Past research has used the blinking of the eyes for this purpose as well as dwell time-based methods, but these techniques are either inconvenient for the user or requires a long time for target selection. Therefore, in this paper, we propose a method for fuzzy system-based target selection for near-infrared (NIR) camera-based gaze trackers. The results of experiments performed in addition to tests of the usability and on-screen keyboard use of the proposed method show that it is better than previous methods. PMID:28420114

  15. Experimental non-classicality of an indivisible quantum system.

    PubMed

    Lapkiewicz, Radek; Li, Peizhe; Schaeff, Christoph; Langford, Nathan K; Ramelow, Sven; Wieśniak, Marcin; Zeilinger, Anton

    2011-06-22

    In contrast to classical physics, quantum theory demands that not all properties can be simultaneously well defined; the Heisenberg uncertainty principle is a manifestation of this fact. Alternatives have been explored--notably theories relying on joint probability distributions or non-contextual hidden-variable models, in which the properties of a system are defined independently of their own measurement and any other measurements that are made. Various deep theoretical results imply that such theories are in conflict with quantum mechanics. Simpler cases demonstrating this conflict have been found and tested experimentally with pairs of quantum bits (qubits). Recently, an inequality satisfied by non-contextual hidden-variable models and violated by quantum mechanics for all states of two qubits was introduced and tested experimentally. A single three-state system (a qutrit) is the simplest system in which such a contradiction is possible; moreover, the contradiction cannot result from entanglement between subsystems, because such a three-state system is indivisible. Here we report an experiment with single photonic qutrits which provides evidence that no joint probability distribution describing the outcomes of all possible measurements--and, therefore, no non-contextual theory--can exist. Specifically, we observe a violation of the Bell-type inequality found by Klyachko, Can, Binicioğlu and Shumovsky. Our results illustrate a deep incompatibility between quantum mechanics and classical physics that cannot in any way result from entanglement.

  16. A deceptive pollination system targeting drosophilids through olfactory mimicry of yeast.

    PubMed

    Stökl, Johannes; Strutz, Antonia; Dafni, Amots; Svatos, Ales; Doubsky, Jan; Knaden, Markus; Sachse, Silke; Hansson, Bill S; Stensmyr, Marcus C

    2010-10-26

    In deceptive pollination, insects are bamboozled into performing nonrewarded pollination. A prerequisite for the evolutionary stability in such systems is that the plants manage to generate a perfect sensory impression of a desirable object in the insect nervous system [1]. The study of these plants can provide important insights into sensory preference of their visiting insects. Here, we present the first description of a deceptive pollination system that specifically targets drosophilid flies. We show that the examined plant (Arum palaestinum) accomplishes its deception through olfactory mimicry of fermentation, a strategy that represents a novel pollination syndrome. The lily odor is composed of volatiles characteristic of yeast, and produces in Drosophila melanogaster an antennal detection pattern similar to that elicited by a range of fermentation products. By functional imaging, we show that the lily odors target a specific subset of odorant receptors (ORs), which include the most conserved OR genes in the drosophilid olfactome. Furthermore, seven of eight visiting drosophilid species show a congruent olfactory response pattern to the lily, in spite of comprising species pairs separated by ∼40 million years [2], showing that the lily targets a basal function of the fly nose, shared by species with similar ecological preference. Copyright © 2010 Elsevier Ltd. All rights reserved.

  17. Laser-induced disruption of systemically administered liposomes for targeted drug delivery

    NASA Astrophysics Data System (ADS)

    Mackanos, Mark A.; Larabi, Malika; Shinde, Rajesh; Simanovskii, Dmitrii M.; Guccione, Samira; Contag, Christopher H.

    2009-07-01

    Liposomal formulations of drugs have been shown to enhance drug efficacy by prolonging circulation time, increasing local concentration and reducing off-target effects. Controlled release from these formulations would increase their utility, and hyperthermia has been explored as a stimulus for targeted delivery of encapsulated drugs. Use of lasers as a thermal source could provide improved control over the release of the drug from the liposomes with minimal collateral tissue damage. Appropriate methods for assessing local release after systemic delivery would aid in testing and development of better formulations. We use in vivo bioluminescence imaging to investigate the spatiotemporal distribution of luciferin, used as a model small molecule, and demonstrate laser-induced release from liposomes in animal models after systemic delivery. These liposomes were tested for luciferin release between 37 and 45 °C in PBS and serum using bioluminescence measurements. In vivo studies were performed on transgenic reporter mice that express luciferase constitutively throughout the body, thus providing a noninvasive readout for controlled release following systemic delivery. An Nd:YLF laser was used (527 nm) to heat tissues and induce rupture of the intravenously delivered liposomes in target tissues. These data demonstrate laser-mediated control of small molecule delivery using thermally sensitive liposomal formulations.

  18. Active imaging system performance model for target acquisition

    NASA Astrophysics Data System (ADS)

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

    2007-04-01

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

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

    PubMed

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

    2016-01-01

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

  20. QCL-based nonlinear sensing of independent targets dynamics.

    PubMed

    Mezzapesa, F P; Columbo, L L; Dabbicco, M; Brambilla, M; Scamarcio, G

    2014-03-10

    We demonstrate a common-path interferometer to measure the independent displacement of multiple targets through nonlinear frequency mixing in a quantum-cascade laser (QCL). The sensing system exploits the unique stability of QCLs under strong optical feedback to access the intrinsic nonlinearity of the active medium. The experimental results using an external dual cavity are in excellent agreement with the numerical simulations based on the Lang-Kobayashi equations.

  1. Programmable Removal of Bacterial Strains by Use of Genome-Targeting CRISPR-Cas Systems

    PubMed Central

    Gomaa, Ahmed A.; Klumpe, Heidi E.; Luo, Michelle L.; Selle, Kurt; Barrangou, Rodolphe; Beisel, Chase L.

    2014-01-01

    ABSTRACT CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of “smart” antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. PMID:24473129

  2. Nanodelivery Systems as New Tools for Immunostimulant or Vaccine Administration: Targeting the Fish Immune System

    PubMed Central

    Ji, Jie; Torrealba, Debora; Ruyra, Àngels; Roher, Nerea

    2015-01-01

    Fish disease treatments have progressed significantly over the last few years and have moved from the massive use of antibiotics to the development of vaccines mainly based on inactivated bacteria. Today, the incorporation of immunostimulants and antigens into nanomaterials provide us with new tools to enhance the performance of immunostimulation. Nanoparticles are dispersions or solid particles designed with specific physical properties (size, surface charge, or loading capacity), which allow controlled delivery and therefore improved targeting and stimulation of the immune system. The use of these nanodelivery platforms in fish is in the initial steps of development. Here we review the advances in the application of nanoparticles to fish disease prevention including: the type of biomaterial, the type of immunostimulant or vaccine loaded into the nanoparticles, and how they target the fish immune system. PMID:26492276

  3. An experimental study of the correlates and consequences of perceiving oneself to be the target of gender discrimination.

    PubMed

    Brown, Christia Spears; Bigler, Rebecca S; Chu, Hui

    2010-10-01

    An experimental methodology was used to test hypotheses concerning the effects of contextual, cognitive-developmental, and individual difference factors on children's views of whether they have been the target of gender discrimination and the possible consequent effect of such views on two forms of state self-esteem: performance and social acceptance. Children (N=108, 5-11 years of age) completed theory of mind and gender attitude measures and a drawing task. Next, children received feedback that was designed to appear either gender biased (discrimination condition) or nonbiased (control condition). Children's attributions for the feedback and state self-esteem were assessed. As expected, children reported having been the target of gender discrimination more often in the discrimination condition than in the control condition. Older and more cognitively advanced children made fewer attributions to discrimination than their peers. Perceptions of discrimination were associated with higher performance state self-esteem and, among egalitarian children, lower social state self-esteem. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Targeted Drug and Gene Delivery Systems for Lung Cancer Therapy

    PubMed Central

    Sundaram, Sneha; Trivedi, Ruchit; Durairaj, Chandrasekar; Ramesh, Rajagopal; Ambati, Balamurali K.; Kompella, Uday B.

    2009-01-01

    Purpose To evaluate the efficacy of a novel docetaxel derivative of deslorelin, a luteinizing hormone releasing hormone (LHRH) agonist, and its combination in-vivo with RGD peptide conjugated nanoparticles encapsulating an anti-angiogenic, anti-VEGF intraceptor (Flt23k) (RGD-Flt23k-NP) in H1299 lung cancer cells and/or xenografts in athymic nude BALB/c mice. Experimental Design The in-vitro and in-vivo efficacy of the deslorelin-docetaxel conjugate (D-D) was evaluated in H1299 cells and xenografts in athymic nude mice. Co-administration of D-D and RGD-Flt23k-NP was tested in-vivo in mice. Tumor inhibition, apoptosis and VEGF inhibition were estimated in each of the treatment groups. Results The conjugate enhanced in-vitro docetaxel efficacy by 13-fold in H1299 cells compared to docetaxel at 24h, and this effect was inhibited following reduction of LHRH-receptor expression by an antisense oligonucleotide. Combination of the conjugate with the RGD-Flt23k-NP in-vivo resulted in an 82- and 15-fold tumor growth inhibition on day 39 following repeated weekly intravenous injections and a single intratumoral injection, respectively. These effects were significantly greater than individual targeted therapies or docetaxel alone. Similarly, apoptotic indices for the combination therapy were 14 and 10% in the intravenous and intratumoral groups, respectively, and higher than the individual therapies. Combination therapy groups exhibited greater VEGF inhibition in both the intravenous and intratumoral groups. Conclusions Docetaxel efficacy was enhanced by LHRH-receptor targeted deslorelin conjugate and further improved by combination with targeted anti-angiogenic nanoparticle gene therapy. Combination of novel targeted therapeutic approaches described here provides an attractive alternative to the current treatment options for lung cancer therapy. PMID:19920099

  5. Experimental system for the control of surgically induced infections

    NASA Technical Reports Server (NTRS)

    Tevebaugh, M. D.

    1971-01-01

    The development tests to be performed on the experimental system are described in detail. The test equipment, conditions, and procedures are given. The portable clean room tests include assembly, collapsability, portability, and storage; laminar flow rate; static pressure; air flow pattern; and electrostatic buildup. The other tests are on the ventilation system, human factors evaluation, electrical subsystem, and material compatibility.

  6. Recent Advances in Nanoparticle-Based Targeted Drug-Delivery Systems Against Cancer and Role of Tumor Microenvironment.

    PubMed

    Ashfaq, Usman Ali; Riaz, Muhammad; Yasmeen, Erum; Yousaf, Muhammad Zubair

    2017-01-01

    Cancer is one of the major causes of death worldwide. The silent activation of cellular factors responsible for deviation from normal regulatory pathways leads to the development of cancer. Nano-biotechnology is a novel drug-delivery system with high potential of efficacy and accuracy to target lethal cancers. Various biocompatible nanoparticle (NP)-based drug-delivery systems such as liposomes, dendrimers, micelles, silica, quantum dots, and magnetic, gold, and carbon nanotubes have already been reported for successful targeted cancer treatment. NPs are functionalized with different biological molecules, peptides, antibody, and protein ligands for targeted drug delivery. These systems include a hydrophilic central core, a target-oriented biocompatible outer layer, and a middle hydrophobic core where the drug destined to reach target site resides. Most of the NPs have the ability to maintain their structural shape and are constructed according to the cancer microenvironment. The self-assembling and colloidal properties of NPs have caused them to become the best vehicles for targeted drug delivery. The tumor microenvironment (TME) plays a major role in cancer progression, detection, and treatment. Due to its continuous complex behavior, the TME can hinder delivery systems, thus halting cancer treatment. Nonetheless, a successful biophysiological interaction between the NPs and the TME results in targeted release of drugs. Currently, a number of drugs and NP-based delivery systems against cancer are in clinical and preclinical trials and a few have been approved by Food and Drug Administration (FDA); for example: taxol, doxil, cerubidine, and adrucil. This review summarizes topical advances about the drugs being used for cancer treatment, their targeted delivery systems based on NPs, and the role of TME in this connection.

  7. Experimental research control software system

    NASA Astrophysics Data System (ADS)

    Cohn, I. A.; Kovalenko, A. G.; Vystavkin, A. N.

    2014-05-01

    A software system, intended for automation of a small scale research, has been developed. The software allows one to control equipment, acquire and process data by means of simple scripts. The main purpose of that development is to increase experiment automation easiness, thus significantly reducing experimental setup automation efforts. In particular, minimal programming skills are required and supervisors have no reviewing troubles. Interactions between scripts and equipment are managed automatically, thus allowing to run multiple scripts simultaneously. Unlike well-known data acquisition commercial software systems, the control is performed by an imperative scripting language. This approach eases complex control and data acquisition algorithms implementation. A modular interface library performs interaction with external interfaces. While most widely used interfaces are already implemented, a simple framework is developed for fast implementations of new software and hardware interfaces. While the software is in continuous development with new features being implemented, it is already used in our laboratory for automation of a helium-3 cryostat control and data acquisition. The software is open source and distributed under Gnu Public License.

  8. An experimental and theoretical model of children’s search behavior in relation to target conspicuity and spatial distribution

    NASA Astrophysics Data System (ADS)

    Rosetti, Marcos Francisco; Pacheco-Cobos, Luis; Larralde, Hernán; Hudson, Robyn

    2010-11-01

    This work explores search trajectories of children attempting to find targets distributed on a playing field. This task, of ludic nature, was developed to test the effect of conspicuity and spatial distribution of targets on the searcher’s performance. The searcher’s path was recorded by a Global Positioning System (GPS) device attached to the child’s waist. Participants were not rewarded nor their performance rated. Variation in the conspicuity of the targets influenced search performance as expected; cryptic targets resulted in slower searches and longer, more tortuous paths. Extracting the main features of the paths showed that the children: (1) paid little attention to the spatial distribution and at least in the conspicuous condition approximately followed a nearest neighbor pattern of target collection, (2) were strongly influenced by the conspicuity of the targets. We implemented a simple statistical model for the search rules mimicking the children’s behavior at the level of individual (coarsened) steps. The model reproduced the main features of the children’s paths without the participation of memory or planning.

  9. An Analytic Model for the Success Rate of a Robotic Actuator System in Hitting Random Targets.

    PubMed

    Bradley, Stuart

    2015-11-20

    Autonomous robotic systems are increasingly being used in a wide range of applications such as precision agriculture, medicine, and the military. These systems have common features which often includes an action by an "actuator" interacting with a target. While simulations and measurements exist for the success rate of hitting targets by some systems, there is a dearth of analytic models which can give insight into, and guidance on optimization, of new robotic systems. The present paper develops a simple model for estimation of the success rate for hitting random targets from a moving platform. The model has two main dimensionless parameters: the ratio of actuator spacing to target diameter; and the ratio of platform distance moved (between actuator "firings") to the target diameter. It is found that regions of parameter space having specified high success are described by simple equations, providing guidance on design. The role of a "cost function" is introduced which, when minimized, provides optimization of design, operating, and risk mitigation costs.

  10. All-reflective optical target illumination system with high numerical aperture

    DOEpatents

    Sigler, Robert D.

    1978-01-01

    An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of co-axially, confluent collimated light beams. A target cavity is defined by a pair of opposed inner ellipsoidal reflectors having respective first focal points within a target region and second focal points at a vertex opening in the opposing reflector. Outwardly of each inner reflector is the opposed combination of a spherical reflector, and an outer generally ellipsoidal reflector having an aberrated first focal point coincident with the focus of the opposing spherical reflector and a second focal point coincident with the second focal point of the opposing inner ellipsoidal reflector through a vertex opening in the spherical reflector. The confluent collimated beams are incident through vertex openings in the outer ellipsoidal reflectors onto respective opposing spherical reflectors. Each beam is reflected by the associated spherical reflector onto the opposing outer ellipsoidal reflector and focused thereby onto the opposing inner ellipsoidal reflector, and then onto the target region.

  11. [The research on a pocket microcontroller system for target controlled infusion].

    PubMed

    Cheng, Yu-Ke; Zhang, Xin-An; Zhang, Yan-Wu; Wu, Qun-Ling; Dou, Jian-Hong; Wang, Rou-Shong

    2005-05-01

    This paper present a microcontroller system for target controlled infusion according to pharmacodynamic parameters of intravenous anesthetics. It can control the depth of anesthesia by adjusting the level of plasma concentrations. The system has the advantages of high precision, extended function and easy operation. It has been now used in the clinical anesthesia.

  12. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

    PubMed

    Feng, Yifan; Wang, Jing; Yuan, Yuanzhi; Zhang, Xi; Shen, Minqian; Yuan, Fei

    2018-03-01

    Stromal cell-derived factor-1 (SDF-1) has been previously confirmed to participate in the formation of choroidal neovascularization (CNV) via its receptor, CXC chemokine receptor (CXCR) 4; CXCR7 is a recently identified receptor for SDF-1. The molecular mechanisms and therapeutic value of CXCR7 in CNV remain undefined. In this study, experimental CNV was induced by laser photocoagulation in Brown-Norway pigmented rats, and aberrant CXCR7 overexpression was detected in the retinal pigment epithelial/choroid/sclera tissues of laser-injured eyes. Blockade of CXCR7 activation via CXCR7 knockdown or neutralizing Ab administration inhibited SDF-1-induced cell survival and the tubular formation of human retinal microvascular endothelial cells (HRMECs) in vitro and reduced CNV leakage and lesion size in vivo. By using microRNA array screening and bioinformatic analyses, we identified miR-539-5p as a regulator of CXCR7. Transfection of HRMECs and choroid-retinal endothelial (RF/6A) cells with the miR-539-5p mimic inhibited their survival and tube formation, whereas CXCR7 overexpression rescued the suppressive effect of miR-539-5p. The antiangiogenic activities of the miR-539-5p mimic were additionally demonstrated in vivo by intravitreal injection. ERK1/2 and AKT signaling downstream of CXCR7 is involved in the miR-539-5p regulation of endothelial cell behaviors. These findings suggest that the manipulation of miR-539-5p/CXCR7 levels may have important therapeutic implications in CNV-associated diseases.-Feng, Y., Wang, J., Yuan, Y., Zhang, X., Shen, M., Yuan, F. miR-539-5p inhibits experimental choroidal neovascularization by targeting CXCR7.

  13. Pharmacotherapy in Generalized Anxiety Disorder: Novel Experimental Medicine Models and Emerging Drug Targets.

    PubMed

    Baldwin, David S; Hou, Ruihua; Gordon, Robert; Huneke, Nathan T M; Garner, Matthew

    2017-04-01

    Many pharmacological and psychological approaches have been found efficacious in patients with generalized anxiety disorder (GAD), but many treatment-seeking patients will not respond and others will relapse despite continuing with interventions that initially had beneficial effects. Other patients will respond but then stop treatment early because of untoward effects such as sexual dysfunction, drowsiness, and weight gain. There is much scope for the development of novel approaches that could have greater overall effectiveness or acceptability than currently available interventions or that have particular effectiveness in specific clinical subgroups. 'Experimental medicine' studies in healthy volunteers model disease states and represent a proof-of-concept approach for the development of novel therapeutic interventions: they determine whether to proceed to pivotal efficacy studies and so can reduce delays in translating innovations into clinical practice. Investigations in healthy volunteers challenged with the inhalation of air 'enriched' with 7.5% carbon dioxide (CO 2 ) indicate this technique provides a validated and robust experimental medicine model, mirroring the subjective, autonomic, and cognitive features of GAD. The anxiety response during CO 2 challenge probably involves both central noradrenergic neurotransmission and effects on acid-base sensitive receptors and so may stimulate development of novel agents targeted at central chemosensors. Increasing awareness of the potential role of altered cytokine balance in anxiety and the interplay of cytokines with monoaminergic mechanisms may also encourage the investigation of novel agents with modulating effects on immunological profiles. Although seemingly disparate, these two approaches to treatment development may pivot on a shared mechanism in exerting anxiolytic-like effects through pharmacological effects on acid-sensing ion channels.

  14. Multisensory System for Fruit Harvesting Robots. Experimental Testing in Natural Scenarios and with Different Kinds of Crops

    PubMed Central

    Fernández, Roemi; Salinas, Carlota; Montes, Héctor; Sarria, Javier

    2014-01-01

    The motivation of this research was to explore the feasibility of detecting and locating fruits from different kinds of crops in natural scenarios. To this end, a unique, modular and easily adaptable multisensory system and a set of associated pre-processing algorithms are proposed. The offered multisensory rig combines a high resolution colour camera and a multispectral system for the detection of fruits, as well as for the discrimination of the different elements of the plants, and a Time-Of-Flight (TOF) camera that provides fast acquisition of distances enabling the localisation of the targets in the coordinate space. A controlled lighting system completes the set-up, increasing its flexibility for being used in different working conditions. The pre-processing algorithms designed for the proposed multisensory system include a pixel-based classification algorithm that labels areas of interest that belong to fruits and a registration algorithm that combines the results of the aforementioned classification algorithm with the data provided by the TOF camera for the 3D reconstruction of the desired regions. Several experimental tests have been carried out in outdoors conditions in order to validate the capabilities of the proposed system. PMID:25615730

  15. Targeted gene deletion of miRNAs in mice by TALEN system.

    PubMed

    Takada, Shuji; Sato, Tempei; Ito, Yoshiaki; Yamashita, Satoshi; Kato, Tomoko; Kawasumi, Miyuri; Kanai-Azuma, Masami; Igarashi, Arisa; Kato, Tomomi; Tamano, Moe; Asahara, Hiroshi

    2013-01-01

    Mice are among the most valuable model animal species with an enormous amount of heritage in genetic modification studies. However, targeting genes in mice is sometimes difficult, especially for small genes, such as microRNAs (miRNAs) and targeting genes in repeat sequences. Here we optimized the application of TALEN system for mice and successfully obtained gene targeting technique in mice for intergenic region and series of microRNAs. Microinjection of synthesized RNA of TALEN targeting each gene in one cell stage of embryo was carried out and injected oocytes were transferred into pseudopregnant ICR female mice, producing a high success rate of the targeted deletion of miRNA genes. In our condition, TALEN RNA without poly(A) tail worked better than that of with poly(A) tail. This mutated allele in miRNA was transmitted to the next generation, suggesting the successful germ line transmission of this targeting method. Consistent with our notion of miRNAs maturation mechanism, in homozygous mutant mice of miR-10a, the non- mutated strand of miRNAs expression was completely diminished. This method will lead us to expand and accelerate our genetic research using mice in a high throughput way.

  16. Systemic combinatorial peptide selection yields a non-canonical iron-mimicry mechanism for targeting tumors in a mouse model of human glioblastoma

    PubMed Central

    Staquicini, Fernanda I.; Ozawa, Michael G.; Moya, Catherine A.; Driessen, Wouter H.P.; Barbu, E. Magda; Nishimori, Hiroyuki; Soghomonyan, Suren; Flores, Leo G.; Liang, Xiaowen; Paolillo, Vincenzo; Alauddin, Mian M.; Basilion, James P.; Furnari, Frank B.; Bogler, Oliver; Lang, Frederick F.; Aldape, Kenneth D.; Fuller, Gregory N.; Höök, Magnus; Gelovani, Juri G.; Sidman, Richard L.; Cavenee, Webster K.; Pasqualini, Renata; Arap, Wadih

    2010-01-01

    The management of CNS tumors is limited by the blood-brain barrier (BBB), a vascular interface that restricts the passage of most molecules from the blood into the brain. Here we show that phage particles targeted with certain ligand motifs selected in vivo from a combinatorial peptide library can cross the BBB under normal and pathological conditions. Specifically, we demonstrated that phage clones displaying an iron-mimic peptide were able to target a protein complex of transferrin and transferrin receptor (TfR) through a non-canonical allosteric binding mechanism and that this functional protein complex mediated transport of the corresponding viral particles into the normal mouse brain. We also showed that, in an orthotopic mouse model of human glioblastoma, a combination of TfR overexpression plus extended vascular permeability and ligand retention resulted in remarkable brain tumor targeting of chimeric adeno-associated virus/phage particles displaying the iron-mimic peptide and carrying a gene of interest. As a proof of concept, we delivered the HSV thymidine kinase gene for molecular-genetic imaging and targeted therapy of intracranial xenografted tumors. Finally, we established that these experimental findings might be clinically relevant by determining through human tissue microarrays that many primary astrocytic tumors strongly express TfR. Together, our combinatorial selection system and results may provide a translational avenue for the targeted detection and treatment of brain tumors. PMID:21183793

  17. Cetuximab-conjugated nanodiamonds drug delivery system for enhanced targeting therapy and 3D Raman imaging.

    PubMed

    Li, Dandan; Chen, Xin; Wang, Hong; Liu, Jie; Zheng, Meiling; Fu, Yang; Yu, Yuan; Zhi, Jinfang

    2017-12-01

    In this study, a multicomponent nanodiamonds (NDs)-based targeting drug delivery system, cetuximab-NDs-cisplatin bioconjugate, combining both specific targeting and enhanced therapeutic efficacy capabilities, is developed and characterized. The specific targeting ability of cetuximab-NDs-cisplatin system on human liver hepatocellular carcinoma (HepG2) cells is evaluated through epidermal growth factor receptor (EGFR) blocking experiments, since EGFR is over-expressed on HepG2 cell membrane. Besides, cytotoxic evaluation confirms that cetuximab-NDs-cisplatin system could significantly inhibit the growth of HepG2 cells, and the therapeutic activity of this system is proven to be better than that of both nonspecific NDs-cisplatin conjugate and specific EGF-NDs-cisplatin conjugate. Furthermore, a 3-dimensional (3D) Raman imaging technique is utilized to visualize the targeting efficacy and enhanced internalization of cetuximab-NDs-cisplatin system in HepG2 cells, using the NDs existing in the bioconjugate as Raman probes, based on the characteristic Raman signal of NDs at 1332 cm -1 . These advantageous properties of cetuximab-NDs-cisplatin system propose a prospective imaging and treatment tool for further diagnostic and therapeutic purposes. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

  18. CCTop: An Intuitive, Flexible and Reliable CRISPR/Cas9 Target Prediction Tool

    PubMed Central

    del Sol Keyer, Maria; Wittbrodt, Joachim; Mateo, Juan L.

    2015-01-01

    Engineering of the CRISPR/Cas9 system has opened a plethora of new opportunities for site-directed mutagenesis and targeted genome modification. Fundamental to this is a stretch of twenty nucleotides at the 5’ end of a guide RNA that provides specificity to the bound Cas9 endonuclease. Since a sequence of twenty nucleotides can occur multiple times in a given genome and some mismatches seem to be accepted by the CRISPR/Cas9 complex, an efficient and reliable in silico selection and evaluation of the targeting site is key prerequisite for the experimental success. Here we present the CRISPR/Cas9 target online predictor (CCTop, http://crispr.cos.uni-heidelberg.de) to overcome limitations of already available tools. CCTop provides an intuitive user interface with reasonable default parameters that can easily be tuned by the user. From a given query sequence, CCTop identifies and ranks all candidate sgRNA target sites according to their off-target quality and displays full documentation. CCTop was experimentally validated for gene inactivation, non-homologous end-joining as well as homology directed repair. Thus, CCTop provides the bench biologist with a tool for the rapid and efficient identification of high quality target sites. PMID:25909470

  19. Experimental examination of frequency locking effect in acousto-optic system

    NASA Astrophysics Data System (ADS)

    Mantsevich, S. N.; Balakshy, V. I.

    2018-04-01

    The optoelectronic system containing collinear acousto-optic cell fabricated on the base of calcium molybdate crystal and positive electronic feedback circuit was examined. The feedback signal is formed due to the optical heterodyning effect that occurs on the cell output and takes place in the special regime of collinear acousto-optic diffraction. It was discovered that three operation modes that may exist in this system. The boundaries between the modes were determined. The positions of the boundaries depend on the main parameters of the system—the incident light intensity and the feedback gain value. The new for acousto-optics phenomenon of acousto-optic system self-oscillations frequency locking by the RF generator signal was discovered and examined experimentally. Such an effect has never been observed before in the acousto-optic systems. It was experimentally shown that frequency locking effect may be used to select one of the multimode semiconductor laser longitudinal modes to improve laser radiation spectral composition.

  20. Orally active-targeted drug delivery systems for proteins and peptides.

    PubMed

    Li, Xiuying; Yu, Miaorong; Fan, Weiwei; Gan, Yong; Hovgaard, Lars; Yang, Mingshi

    2014-09-01

    In the past decade, extensive efforts have been devoted to designing 'active targeted' drug delivery systems (ATDDS) to improve oral absorption of proteins and peptides. Such ATDDS enhance cellular internalization and permeability of proteins and peptides via molecular recognition processes such as ligand-receptor or antigen-antibody interaction, and thus enhance drug absorption. This review focuses on recent advances with orally ATDDS, including ligand-protein conjugates, recombinant ligand-protein fusion proteins and ligand-modified carriers. In addition to traditional intestinal active transport systems of substrates and their corresponding receptors, transporters and carriers, new targets such as intercellular adhesion molecule-1 and β-integrin are also discussed. ATDDS can improve oral absorption of proteins and peptides. However, currently, no clinical studies on ATDDS for proteins and peptides are underway, perhaps due to the complexity and limited knowledge of transport mechanisms. Therefore, more research is warranted to optimize ATDDS efficiency.

  1. All-reflective optical target illumination system with high numerical aperture

    DOEpatents

    Thomas, Carlton E.; Sigler, Robert D.; Hoeger, John G.

    1979-01-01

    An all-reflective optical system for providing illumination of a target focal region at high numerical aperture from a pair of confluent collimated light beams. The collimated beams are each incident upon an associated concave eccentric pupil paraboloidal reflective surface, and thereby each focused through an opening in an associated outer ellipsoidal reflective surface onto a plane reflector. Each beam is reflected by its associated plane reflector onto the opposing concave surface of the outer ellipsoids to be focused through an opening in the plane surface onto an opposing inner concave ellipsoidal reflective surface, and thence onto the target region.

  2. Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus

    PubMed Central

    Guan, Jing; Wang, Wanying

    2017-01-01

    ABSTRACT CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCCmec). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5′ tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCCmec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and

  3. Chromosomal Targeting by the Type III-A CRISPR-Cas System Can Reshape Genomes in Staphylococcus aureus.

    PubMed

    Guan, Jing; Wang, Wanying; Sun, Baolin

    2017-01-01

    CRISPR-Cas (clustered regularly interspaced short palindromic repeat [CRISPR]-CRISPR-associated protein [Cas]) systems can provide protection against invading genetic elements by using CRISPR RNAs (crRNAs) as a guide to locate and degrade the target DNA. CRISPR-Cas systems have been classified into two classes and five types according to the content of cas genes. Previous studies have indicated that CRISPR-Cas systems can avoid viral infection and block plasmid transfer. Here we show that chromosomal targeting by the Staphylococcus aureus type III-A CRISPR-Cas system can drive large-scale genome deletion and alteration within integrated staphylococcal cassette chromosome mec (SCC mec ). The targeting activity of the CRISPR-Cas system is associated with the complementarity between crRNAs and protospacers, and 10- to 13-nucleotide truncations of spacers partially block CRISPR attack and more than 13-nucleotide truncation can fully abolish targeting, suggesting that a minimal length is required to license cleavage. Avoiding base pairings in the upstream region of protospacers is also necessary for CRISPR targeting. Successive trinucleotide complementarity between the 5' tag of crRNAs and protospacers can disrupt targeting. Our findings reveal that type III-A CRISPR-Cas systems can modulate bacterial genome stability and may serve as a high-efficiency tool for deleting resistance or virulence genes in bacteria. IMPORTANCE Staphylococcus aureus is a pathogen that can cause a wide range of infections in humans. Studies have suggested that CRISPR-Cas systems can drive the loss of integrated mobile genetic elements (MGEs) by chromosomal targeting. Here we demonstrate that CRISPR-mediated cleavage contributes to the partial deletion of integrated SCC mec in methicillin-resistant S. aureus (MRSA), which provides a strategy for the treatment of MRSA infections. The spacer within artificial CRISPR arrays should contain more than 25 nucleotides for immunity, and consecutive

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

    PubMed

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

    2018-01-08

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

  5. Experimental evaluation of a neural-oscillator-driven active mass damper system

    NASA Astrophysics Data System (ADS)

    Iba, Daisuke; Hongu, Junichi

    2014-03-01

    This paper proposes a new active dynamic absorber control system for high-rise buildings using a neural oscillator and a map, which estimates the amplitude level of the oscillator, and shows some experimental results by using an apparatus, which realizes the proposed control algorithm. The proposed system decides the travel distance and direction of the auxiliary mass of the dynamic absorber using the output of oscillator, which is the filtering result of structure acceleration responses by the property of the oscillator, and Amplitude-Phase map (AP-map) for estimation of the structural response in specific frequency between synchronization region, and then, transfer the auxiliary mass to the predetermined location by using a position controller. In addition, the developed active dynamic absorber system is mounted on the top of the experimental single degree of freedom structure, which represents high-rise buildings, and consists of the auxiliary mass, a DC motor, a ball screw, a microcomputer, a laser displacement sensor, and an acceleration sensor. The proposed AP-map and the algorithm to determine the travel direction of the mass using the oscillator output are embedded in the microcomputer. This paper starts by illuminating the relation among subsystems of the proposed system with reference to a block diagram, and then, shows experimental responses of the whole system excited by earthquakes to confirm the validity of the proposed system.

  6. New generation of oral mucosal vaccines targeting dendritic cells

    PubMed Central

    Owen, Jennifer L.; Sahay, Bikash; Mohamadzadeh, Mansour

    2013-01-01

    As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including B. anthracis in experimental models of disease. PMID:23835515

  7. Simultaneously targeting inflammatory response and parasite sequestration in brain to treat Experimental Cerebral Malaria

    PubMed Central

    Dende, Chaitanya; Meena, Jairam; Nagarajan, Perumal; Panda, Amulya K.; Rangarajan, Pundi N.; Padmanaban, Govindarajan

    2015-01-01

    Malaria afflicts around 200 million people annually, with a mortality number close to 600,000. The mortality rate in Human Cerebral Malaria (HCM) is unacceptably high (15–20%), despite the availability of artemisinin-based therapy. An effective adjunct therapy is urgently needed. Experimental Cerebral Malaria (ECM) in mice manifests many of the neurological features of HCM. Migration of T cells and parasite-infected RBCs (pRBCs) into the brain are both necessary to precipitate the disease. We have been able to simultaneously target both these parameters of ECM. Curcumin alone was able to reverse all the parameters investigated in this study that govern inflammatory responses, CD8+ T cell and pRBC sequestration into the brain and blood brain barrier (BBB) breakdown. But the animals eventually died of anemia due to parasite build-up in blood. However, arteether-curcumin (AC) combination therapy even after the onset of symptoms provided complete cure. AC treatment is a promising therapeutic option for HCM. PMID:26227888

  8. Experimental Investigation of the Properties of an Acoustic Wave Induced by Laser Ablation of a Solid Target in Water-Confined Plasma Propulsion

    NASA Astrophysics Data System (ADS)

    Zheng, Zhiyuan; Gao, Hua; Gao, Lu; Xing, Jie

    2014-11-01

    Acoustic waves generated in nanosecond pulsed-laser ablation of a solid target in both air and water-confined environments were measured experimentally. It was found that the amplitude of the acoustic wave tended to decrease with an increase in water thickness. The waves were analyzed by means of fast Fourier transform. It was shown that there are several frequency components in the acoustic waves with the dominant frequency shifting from high frequency to low frequency as the thickness of the water layer increases. Furthermore, strong acoustic pressure led to enhancement of the coupling of the laser energy to the target in laser plasma propulsion.

  9. Atmosphere Behavior in Gas-Closed Mouse-Algal Systems: An Experimental and Modelling Study

    NASA Technical Reports Server (NTRS)

    Averner, M. M.; Moore, B., III; Bartholomew, I.; Wharton, R.

    1985-01-01

    A dual approach of mathematical modelling and laboratory experimentation aimed at examining the gas exchange characteristics of artificial animal/plant systems closed to the ambient atmosphere was initiated. The development of control techniques and management strategies for maintaining the atmospheric levels of carbon dioxide and oxygen at physiological levels is examined. A mathematical model simulating the atmospheric behavior in these systems was developed and an experimental gas closed system was constructed. These systems are described and preliminary results are presented.

  10. Experimental and computational investigation of lateral gauge response in polycarbonate

    NASA Astrophysics Data System (ADS)

    Eliot, Jim; Harris, Ernst; Hazell, Paul; Appleby-Thomas, Gareth; Winter, Ronald; Wood, David; Owen, Gareth

    2011-06-01

    Polycarbonate's use in personal armour systems means its high strain-rate response has been extensively studied. Interestingly, embedded lateral manganin stress gauges in polycarbonate have shown gradients behind incident shocks, suggestive of increasing shear strength. However, such gauges need to be embedded in a central (typically) epoxy interlayer - an inherently invasive approach. Recently, research has suggested that in such metal systems interlayer/target impedance may contribute to observed gradients in lateral stress. Here, experimental T-gauge (Vishay Micro-Measurements® type J2M-SS-580SF-025) traces from polycarbonate targets are compared to computational simulations. This work extends previous efforts such that similar impedance exists between the interlayer and matrix (target) interface. Further, experiments and simulations are presented investigating the effects of a ``dry joint'' in polycarbonate, in which no encapsulating medium is employed.

  11. Drivers' detection of roadside targets when driving vehicles with three headlight systems during high beam activation.

    PubMed

    Reagan, Ian J; Brumbelow, Matthew L

    2017-02-01

    A previous open-road experiment indicated that curve-adaptive HID headlights driven with low beams improved drivers' detection of low conspicuity targets compared with fixed halogen and fixed HID low beam systems. The current study used the same test environment and targets to assess whether drivers' detection of targets was affected by the same three headlight systems when using high beams. Twenty drivers search and responded for 60 8×12inch targets of high or low reflectance that were distributed evenly across straight and curved road sections as they drove at 30 mph on an unlit two-lane rural road. The results indicate that target detection performance was generally similar across the three systems. However, one interaction indicated that drivers saw low reflectance targets on straight road sections from further away when driving with the fixed halogen high beam condition compared with curve-adaptive HID high beam headlights and also indicated a possible benefit for the curve-adaptive HID high beams for high reflectance targets placed on the inside of curves. The results of this study conflict with the previous study of low beams, which showed a consistent benefit for the curve-adaptive HID low beams for targets placed on curves compared with fixed HID and fixed halogen low beam conditions. However, a comparison of mean detection distances from the two studies indicated uniformly longer mean target detection distances for participants driving with high beams and implicates the potential visibility benefits for systems that optimize proper high beam use. Copyright © 2016 Elsevier Ltd. All rights reserved.

  12. Experimentation and evaluation of advanced integrated system concepts

    NASA Astrophysics Data System (ADS)

    Ross, M.; Garrigus, K.; Gottschalck, J.; Rinearson, L.; Longee, E.

    1980-09-01

    This final report examines the implementation of a time-phased test bed for experimentation and evaluation of advanced system concepts relative to the future Defense Switched Network (DSN). After identifying issues pertinent to the DSN, a set of experiments which address these issues are developed. Experiments are ordered based on their immediacy and relative importance to DSN development. The set of experiments thus defined allows requirements for a time phased implementation of a test bed to be identified, and several generic test bed architectures which meet these requirements are examined. Specific architecture implementations are costed and cost/schedule profiles are generated as a function of experimental capability. The final recommended system consists of two separate test beds: a circuit switch test bed, configured around an off-the-shelf commercial switch, and directed toward the examination of nearer term and transitional issues raised by the evolving DSN; and a packet/hybrid test bed, featuring a discrete buildup of new hardware and software modules, and directed toward examination of the more advanced integrated voice and data telecommunications issues and concepts.

  13. Systems biology approaches and tools for analysis of interactomes and multi-target drugs.

    PubMed

    Schrattenholz, André; Groebe, Karlfried; Soskic, Vukic

    2010-01-01

    Systems biology is essentially a proteomic and epigenetic exercise because the relatively condensed information of genomes unfolds on the level of proteins. The flexibility of cellular architectures is not only mediated by a dazzling number of proteinaceous species but moreover by the kinetics of their molecular changes: The time scales of posttranslational modifications range from milliseconds to years. The genetic framework of an organism only provides the blue print of protein embodiments which are constantly shaped by external input. Indeed, posttranslational modifications of proteins represent the scope and velocity of these inputs and fulfil the requirements of integration of external spatiotemporal signal transduction inside an organism. The optimization of biochemical networks for this type of information processing and storage results in chemically extremely fine tuned molecular entities. The huge dynamic range of concentrations, the chemical diversity and the necessity of synchronisation of complex protein expression patterns pose the major challenge of systemic analysis of biological models. One further message is that many of the key reactions in living systems are essentially based on interactions of moderate affinities and moderate selectivities. This principle is responsible for the enormous flexibility and redundancy of cellular circuitries. In complex disorders such as cancer or neurodegenerative diseases, which initially appear to be rooted in relatively subtle dysfunctions of multimodal physiologic pathways, drug discovery programs based on the concept of high affinity/high specificity compounds ("one-target, one-disease"), which has been dominating the pharmaceutical industry for a long time, increasingly turn out to be unsuccessful. Despite improvements in rational drug design and high throughput screening methods, the number of novel, single-target drugs fell much behind expectations during the past decade, and the treatment of "complex

  14. Mitochondrial Targets for Pharmacological Intervention in Human Disease

    PubMed Central

    2015-01-01

    Over the past several years, mitochondrial dysfunction has been linked to an increasing number of human illnesses, making mitochondrial proteins (MPs) an ever more appealing target for therapeutic intervention. With 20% of the mitochondrial proteome (312 of an estimated 1500 MPs) having known interactions with small molecules, MPs appear to be highly targetable. Yet, despite these targeted proteins functioning in a range of biological processes (including induction of apoptosis, calcium homeostasis, and metabolism), very few of the compounds targeting MPs find clinical use. Recent work has greatly expanded the number of proteins known to localize to the mitochondria and has generated a considerable increase in MP 3D structures available in public databases, allowing experimental screening and in silico prediction of mitochondrial drug targets on an unprecedented scale. Here, we summarize the current literature on clinically active drugs that target MPs, with a focus on how existing drug targets are distributed across biochemical pathways and organelle substructures. Also, we examine current strategies for mitochondrial drug discovery, focusing on genetic, proteomic, and chemogenomic assays, and relevant model systems. As cell models and screening techniques improve, MPs appear poised to emerge as relevant targets for a wide range of complex human diseases, an eventuality that can be expedited through systematic analysis of MP function. PMID:25367773

  15. Target recognition in passive terahertz image of human body

    NASA Astrophysics Data System (ADS)

    Zhao, Ran; Zhao, Yuan-meng; Deng, Chao; Zhang, Cun-lin; Li, Yue

    2014-11-01

    THz radiation can penetrate through many nonpolar dielectric materials and can be used for nondestructive/noninvasive sensing and imaging of targets under nonpolar, nonmetallic covers or containers. Thus using THz systems to "see through" concealing barriers (i.e. packaging, corrugated cardboard, clothing) has been proposed as a new security screening method. Objects that can be detected by THz include concealed weapons, explosives, and chemical agents under clothing. Passive THz imaging system can detect THz wave from human body without transmit any electromagnetic wave, and the suspicious objects will become visible because the THz wave is blocked by this items. We can find out whether or not someone is carrying dangerous objects through this image. In this paper, the THz image enhancement, segmentation and contour extraction algorithms were studied to achieve effective target image detection. First, the terahertz images are enhanced and their grayscales are stretched. Then we apply global threshold segmentation to extract the target, and finally the targets are marked on the image. Experimental results showed that the algorithm proposed in this paper can extract and mark targets effectively, so that people can identify suspicious objects under clothing quickly. The algorithm can significantly improve the usefulness of the terahertz security apparatus.

  16. Texture orientation-based algorithm for detecting infrared maritime targets.

    PubMed

    Wang, Bin; Dong, Lili; Zhao, Ming; Wu, Houde; Xu, Wenhai

    2015-05-20

    Infrared maritime target detection is a key technology for maritime target searching systems. However, in infrared maritime images (IMIs) taken under complicated sea conditions, background clutters, such as ocean waves, clouds or sea fog, usually have high intensity that can easily overwhelm the brightness of real targets, which is difficult for traditional target detection algorithms to deal with. To mitigate this problem, this paper proposes a novel target detection algorithm based on texture orientation. This algorithm first extracts suspected targets by analyzing the intersubband correlation between horizontal and vertical wavelet subbands of the original IMI on the first scale. Then the self-adaptive wavelet threshold denoising and local singularity analysis of the original IMI is combined to remove false alarms further. Experiments show that compared with traditional algorithms, this algorithm can suppress background clutter much better and realize better single-frame detection for infrared maritime targets. Besides, in order to guarantee accurate target extraction further, the pipeline-filtering algorithm is adopted to eliminate residual false alarms. The high practical value and applicability of this proposed strategy is backed strongly by experimental data acquired under different environmental conditions.

  17. Experimental grid connected PV system power analysis

    NASA Astrophysics Data System (ADS)

    Semaoui, Smail; Abdeladim, Kamel; Arab, Amar Hadj; Boulahchich, Saliha; Amrouche, Said Ould; Yassaa, Noureddine

    2018-05-01

    Almost 80 % of Algerian territory is appropriate for the exploitation of solar energy. The Algerian energetic strategy provides a substantial injection of PV electricity to the national grid. Currently, about 344 MWp of PV arrays which corresponds approximately to 2,34 km2 of module surfaces, are connected on electricity grid over the national territory. The Algerian Northern regions are characterized by strong pollution and high humidity. These phenomena affect the energetic productivity of PV generator. The objective of our study is to analyze experimental grid connected PV system power in coastal locations. Hence, experiments have been conducted on three identical PV systems to determine the electrical performances. Transformer-less inverters are the most attractive for the ground-based photovoltaic (PV) system due to their efficiencies, reduced cost and weight. Besides, the absence of the galvanic isolation generates problems of capacitive leakage current on the AC side and the degradation of the insulation resistance on the DC side of the inverter. In this work, experimental study of the behavior of single-phase inverters without transformers is presented. The main objective of this work is to study the degradation of the insulation resistance at the input of the inverter, and the capacitive leakage current at the output of the inverter. This study was achieved at the CDER on a rainy day of 15/03/2017, on the first PV plant connected to the low voltage network in Algeria. This investigation can help forecasting the PV array energetic production by taking into account natural conditions.

  18. REQUIREMENTS AND GUIDELINES FOR NSLS EXPERIMENTAL BEAM LINE VACUUM SYSTEMS-REVISION B.

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

    FOERSTER,C.

    Typical beam lines are comprised of an assembly of vacuum valves and shutters referred to as a ''front end'', optical elements to monochromatize, focus and split the photon beam, and an experimental area where a target sample is placed into the photon beam and data from the interaction is detected and recorded. Windows are used to separate sections of beam lines that are not compatible with storage ring ultra high vacuum. Some experimental beam lines share a common vacuum with storage rings. Sections of beam lines are only allowed to vent up to atmospheric pressure using pure nitrogen gas aftermore » a vacuum barrier is established to protect ring vacuum. The front end may only be bled up when there is no current in the machine. This is especially true on the VUV storage ring where for most experiments, windows are not used. For the shorter wavelength, more energetic photons of the x-ray ring, beryllium windows are used at various beam line locations so that the monochromator, mirror box or sample chamber may be used in a helium atmosphere or rough vacuum. The window separates ring vacuum from the environment of the downstream beam line components. The stored beam lifetime in the storage rings and the maintenance of desirable reflection properties of optical surfaces depend upon hydrocarbon-free, ultra-high vacuum systems. Storage ring vacuum systems will operate at pressures of {approximately} 1 x 10{sup {minus}10} Torr without beam and {approximately} 1 x 10{sup {minus}9} Torr with beam. Systems are free of hydrocarbons in the sense that no pumps, valves, etc. containing organics are used. Components are all-metal, chemically cleaned and bakeable. To the extent that beam lines share a common vacuum with the storage ring, the same criteria will hold for beam line components. The design philosophy for NSLS beam lines is to use all-metal, hydrocarbon-free front end components and recommend that experimenters use this approach for common vacuum hardware downstream

  19. Non-Linear System Identification for Aeroelastic Systems with Application to Experimental Data

    NASA Technical Reports Server (NTRS)

    Kukreja, Sunil L.

    2008-01-01

    Representation and identification of a non-linear aeroelastic pitch-plunge system as a model of the NARMAX class is considered. A non-linear difference equation describing this aircraft model is derived theoretically and shown to be of the NARMAX form. Identification methods for NARMAX models are applied to aeroelastic dynamics and its properties demonstrated via continuous-time simulations of experimental conditions. Simulation results show that (i) the outputs of the NARMAX model match closely those generated using continuous-time methods and (ii) NARMAX identification methods applied to aeroelastic dynamics provide accurate discrete-time parameter estimates. Application of NARMAX identification to experimental pitch-plunge dynamics data gives a high percent fit for cross-validated data.

  20. [Advances of tumor targeting peptides drug delivery system with pH-sensitive activities].

    PubMed

    Ma, Yin-yun; Li, Li; Huang, Hai-feng; Gou, San-hu; Ni, Jing-man

    2016-05-01

    The pH-sensitive peptides drug delivery systems, which target to acidic extracellular environment of tumor tissue, have many advantages in drug delivery. They exhibit a high specificity to tumor and low cytotoxicity, which significantly increase the efficacy of traditional anti-cancer drugs. In recent years the systems have received a great attention. The pH-sensitive peptides drug delivery systems can be divided into five types according to the difference in pH-responsive mechanism,type of peptides and carrier materials. This paper summarizes the recent progresses in the field with a focus on the five types of pH-sensitive peptides in drug delivery systems. This may provide a guideline to design and application of tumor targeting drugs.

  1. Hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation system for cancer gene therapy

    PubMed Central

    Javan, Bita; Shahbazi, Majid

    2017-01-01

    Transcriptional targeting is the best approach for specific gene therapy. Hypoxia is a common feature of the tumour microenvironment. Therefore, targeting gene expression in hypoxic cells by placing transgene under the control of a hypoxia-responsive promoter can be a good strategy for cancer-specific gene therapy. The hypoxia-inducible gene expression system has been investigated more in suicide gene therapy and it can also be of great help in knocking down cancer gene therapy with siRNAs. However, this system needs to be optimised to have maximum efficacy with minimum side effects in normal tissues. The combination of tissue-/tumour-specific promoters with HRE core sequences has been found to enhance the specificity and efficacy of this system. In this review, hypoxia-inducible gene expression system as well as gene therapy strategies targeting tumour hypoxia will be discussed. This review will also focus on hypoxia-inducible tumour-specific promoters as a dual-targeting transcriptional regulation systems developed for cancer-specific gene therapy. PMID:28798809

  2. [Targeted drug delivery system: potential application to resveratrol].

    PubMed

    Farghali, Hassan; Kameníková, Ludmila

    2017-01-01

    Drug delivery system (DDS) is intended to increasing effectiveness of drugs through targeted distribution and to reducing of unwanted effects. In this mini-review, the basic principles of nanotechnology that were developed for DDS were reported including sections on the present research in key areas that are important for future investigations. Attention is paid on resveratrol as a model phytochemical with interesting pharmacologic profile which was demonstrated in great numbers of studies and for its wide use as supplemental therapy. Due to complicated pharmacokinetic profile of resveratrol that is characterized by very low bioavailability in spite of high oral absorption, the effects of resveratrol is being studied in new nanotechnology preparations of pharmaceutical formulation. Herein we report on results of present in vitro and in vivo investigations with resveratrol in new types of drug formulations using different nanoparticles as liposomes, solid lipid particles, cyclodextrins and micelles.Key words: targeted drug delivery nanotechnology resveratrol.

  3. Effect of the target power density on high-power impulse magnetron sputtering of copper

    NASA Astrophysics Data System (ADS)

    Kozák, Tomáš

    2012-04-01

    We present a model analysis of high-power impulse magnetron sputtering of copper. We use a non-stationary global model based on the particle and energy conservation equations in two zones (the high density plasma ring above the target racetrack and the bulk plasma region), which makes it possible to calculate time evolutions of the averaged process gas and target material neutral and ion densities, as well as the fluxes of these particles to the target and substrate during a pulse period. We study the effect of the increasing target power density under conditions corresponding to a real experimental system. The calculated target current waveforms show a long steady state and are in good agreement with the experimental results. For an increasing target power density, an analysis of the particle densities shows a gradual transition to a metal dominated discharge plasma with an increasing degree of ionization of the depositing flux. The average fraction of target material ions in the total ion flux onto the substrate is more than 90% for average target power densities higher than 500 W cm-2 in a pulse. The average ionized fraction of target material atoms in the flux onto the substrate reaches 80% for a maximum average target power density of 3 kW cm-2 in a pulse.

  4. Programmable removal of bacterial strains by use of genome-targeting CRISPR-Cas systems.

    PubMed

    Gomaa, Ahmed A; Klumpe, Heidi E; Luo, Michelle L; Selle, Kurt; Barrangou, Rodolphe; Beisel, Chase L

    2014-01-28

    CRISPR (clustered regularly interspaced short palindromic repeats)-Cas (CRISPR-associated) systems in bacteria and archaea employ CRISPR RNAs to specifically recognize the complementary DNA of foreign invaders, leading to sequence-specific cleavage or degradation of the target DNA. Recent work has shown that the accidental or intentional targeting of the bacterial genome is cytotoxic and can lead to cell death. Here, we have demonstrated that genome targeting with CRISPR-Cas systems can be employed for the sequence-specific and titratable removal of individual bacterial strains and species. Using the type I-E CRISPR-Cas system in Escherichia coli as a model, we found that this effect could be elicited using native or imported systems and was similarly potent regardless of the genomic location, strand, or transcriptional activity of the target sequence. Furthermore, the specificity of targeting with CRISPR RNAs could readily distinguish between even highly similar strains in pure or mixed cultures. Finally, varying the collection of delivered CRISPR RNAs could quantitatively control the relative number of individual strains within a mixed culture. Critically, the observed selectivity and programmability of bacterial removal would be virtually impossible with traditional antibiotics, bacteriophages, selectable markers, or tailored growth conditions. Once delivery challenges are addressed, we envision that this approach could offer a novel means to quantitatively control the composition of environmental and industrial microbial consortia and may open new avenues for the development of "smart" antibiotics that circumvent multidrug resistance and differentiate between pathogenic and beneficial microorganisms. Controlling the composition of microbial populations is a critical aspect in medicine, biotechnology, and environmental cycles. While different antimicrobial strategies, such as antibiotics, antimicrobial peptides, and lytic bacteriophages, offer partial solutions

  5. Mercury Handling for the Target System for a Muon Collider

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

    Graves, Van B; Mcdonald, K; Kirk, H.

    2012-01-01

    The baseline target concept for a Muon Collider or Neutrino Factory is a free-stream mercury jet being impacted by an 8-GeV proton beam. The target is located within a 20-T magnetic field, which captures the generated pions that are conducted to a downstream decay channel. Both the mercury and the proton beam are introduced at slight downward angles to the magnetic axis. A pool of mercury serves as a receiving reservoir for the mercury and a dump for the unexpended proton beam. The impact energy of the remaining beam and jet are substantial, and it is required that splashes andmore » waves be controlled in order to minimize the potential for interference of pion production at the target. Design issues discussed in this paper include the nozzle, splash mitigation in the mercury pool, the mercury containment vessel, and the mercury recirculation system.« less

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

    NASA Technical Reports Server (NTRS)

    Gomaa, Hassan; Kerschberg, Larry; Sugumaran, Vijayan

    1992-01-01

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

  7. A systems-based food safety evaluation: an experimental approach.

    PubMed

    Higgins, Charles L; Hartfield, Barry S

    2004-11-01

    Food establishments are complex systems with inputs, subsystems, underlying forces that affect the system, outputs, and feedback. Building on past exploration of the hazard analysis critical control point concept and Ludwig von Bertalanffy General Systems Theory, the National Park Service (NPS) is attempting to translate these ideas into a realistic field assessment of food service establishments and to use information gathered by these methods in efforts to improve food safety. Over the course of the last two years, an experimental systems-based methodology has been drafted, developed, and tested by the NPS Public Health Program. This methodology is described in this paper.

  8. Bipartite recognition of target RNAs activates DNA cleavage by the Type III-B CRISPR–Cas system

    PubMed Central

    Elmore, Joshua R.; Sheppard, Nolan F.; Ramia, Nancy; Deighan, Trace; Li, Hong; Terns, Rebecca M.; Terns, Michael P.

    2016-01-01

    CRISPR–Cas systems eliminate nucleic acid invaders in bacteria and archaea. The effector complex of the Type III-B Cmr system cleaves invader RNAs recognized by the CRISPR RNA (crRNA ) of the complex. Here we show that invader RNAs also activate the Cmr complex to cleave DNA. As has been observed for other Type III systems, Cmr eliminates plasmid invaders in Pyrococcus furiosus by a mechanism that depends on transcription of the crRNA target sequence within the plasmid. Notably, we found that the target RNA per se induces DNA cleavage by the Cmr complex in vitro. DNA cleavage activity does not depend on cleavage of the target RNA but notably does require the presence of a short sequence adjacent to the target sequence within the activating target RNA (rPAM [RNA protospacer-adjacent motif]). The activated complex does not require a target sequence (or a PAM) in the DNA substrate. Plasmid elimination by the P. furiosus Cmr system also does not require the Csx1 (CRISPR-associated Rossman fold [CARF] superfamily) protein. Plasmid silencing depends on the HD nuclease and Palm domains of the Cmr2 (Cas10 superfamily) protein. The results establish the Cmr complex as a novel DNA nuclease activated by invader RNAs containing a crRNA target sequence and a rPAM. PMID:26848045

  9. Progress on LMJ targets for ignition

    NASA Astrophysics Data System (ADS)

    Cherfils-Clérouin, C.; Boniface, C.; Bonnefille, M.; Dattolo, E.; Galmiche, D.; Gauthier, P.; Giorla, J.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Masson-Laborde, P. E.; Monteil, M. C.; Poggi, F.; Seytor, P.; Wagon, F.; Willien, J. L.

    2009-12-01

    Targets designed to produce ignition on the Laser Megajoule (LMJ) are being simulated in order to set specifications for target fabrication. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4 MJ and 380 TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-ball shaped cocktail hohlraum; with these improvements, a target based on the 240-beam A1040 capsule can be included in the 160-beam laser energy-power space. Robustness evaluations of these different targets shed light on critical points for ignition, which can trade off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  10. Lithium target performance evaluation for low-energy accelerator-based in vivo measurements using gamma spectroscopy.

    PubMed

    Aslam; Prestwich, W V; McNeill, F E

    2003-03-01

    The operating conditions at McMaster KN Van de Graaf accelerator have been optimized to produce neutrons via the (7)Li(p, n)(7)Be reaction for in vivo neutron activation analysis. In a number of earlier studies (development of an accelerator based system for in vivo neutron activation analysis measurements of manganese in humans, Ph.D. Thesis, McMaster University, Hamilton, ON, Canada; Appl. Radiat. Isot. 53 (2000) 657; in vivo measurement of some trace elements in human Bone, Ph.D. Thesis. McMaster University, Hamilton, ON, Canada), a significant discrepancy between the experimental and the calculated neutron doses has been pointed out. The hypotheses formulated in the above references to explain the deviation of the experimental results from analytical calculations, have been tested experimentally. The performance of the lithium target for neutron production has been evaluated by measuring the (7)Be activity produced as a result of (p, n) interaction with (7)Li. In contradiction to the formulated hypotheses, lithium target performance was found to be mainly affected by inefficient target cooling and the presence of oxides layer on target surface. An appropriate choice of these parameters resulted in neutron yields same as predicated by analytical calculations.

  11. The application and research of the multi-receiving telescopes technology in laser ranging to space targets

    NASA Astrophysics Data System (ADS)

    Wu, Zhibo; Zhang, Haifeng; Zhang, Zhongping; Deng, Huarong; Li, Pu; Meng, Wendong; Cheng, Zhien; Shen, Lurun; Tang, Zhenhong

    2014-11-01

    Laser ranging technology can directly measure the distance between space targets and ground stations with the highest measurement precision and will play an irreplaceable role in orbit check and calibrating microwave measurement system. The precise orbit determination and accurate catalogue of space targets can also be realized by laser ranging with multi-stations. Among space targets, most of ones are inactive targets and space debris, which should be paid the great attentions for the safety of active spacecrafts. Because of laser diffuse reflection from the surface of targets, laser ranging to space debris has the characteristics of wide coverage and weak strength of laser echoes, even though the powerful laser system is applied. In order to increase the receiving ability of laser echoes, the large aperture telescope should be adopted. As well known, some disadvantages for one set of large aperture telescope, technical development difficulty and system running and maintenance complexity, will limit its flexible applications. The multi-receiving telescopes technology in laser ranging to space targets is put forward to realize the equivalent receiving ability produced by one larger aperture telescope by way of using multi-receiving telescopes, with the advantages of flexibility and maintenance. The theoretical analysis of the feasibility and key technologies of multi-receiving telescopes technology in laser ranging to space targets are presented in this paper. The experimental measurement system based on the 60cm SLR system and 1.56m astronomical telescopes with a distance of about 50m is established to provide the platform for researching on the multi-receiving telescopes technology. The laser ranging experiments to satellites equipped with retro-reflectors are successfully performed by using the above experimental system and verify the technical feasibility to increase the ability of echo detection. And the multi-receiving telescopes technology will become a

  12. Peptide and low molecular weight proteins based kidney targeted drug delivery systems.

    PubMed

    Xu, Pengfei; Zhang, Hailiang; Dang, Ruili; Jiang, Pei

    2018-05-30

    Renal disease is a worldwide public health problem, and unfortunately, the therapeutic index of regular drugs is limited. Thus, it is a great need to develop effective treatment strategies. Among the reported strategies, kidney-targeted drug delivery system is a promising method to increase renal efficacy and reduce extra-renal toxicity. In recent years, working as vehicles for targeted drug delivery, low molecular weight proteins (LMWP) and peptide have received immense attention due to their many advantages, such as selective accumulation in kidney, high drug loading capability, control over routes of biodegradation, convenience in modification at the amino terminus, and good biocompatibility. In this review, we describe the current LMWP and peptide carriers for kidney targeted drug delivery systems. In addition, we discuss different linking strategies between carriers and drugs. Furthermore, we briefly outline the current status and attempt to give an outlook on the further study. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  13. The development of a multi-target compiler-writing system for flight software development

    NASA Technical Reports Server (NTRS)

    Feyock, S.; Donegan, M. K.

    1977-01-01

    A wide variety of systems designed to assist the user in the task of writing compilers has been developed. A survey of these systems reveals that none is entirely appropriate to the purposes of the MUST project, which involves the compilation of one or at most a small set of higher-order languages to a wide variety of target machines offering little or no software support. This requirement dictates that any compiler writing system employed must provide maximal support in the areas of semantics specification and code generation, the areas in which existing compiler writing systems as well as theoretical underpinnings are weakest. This paper describes an ongoing research and development effort to create a compiler writing system which will overcome these difficulties, thus providing a software system which makes possible the fast, trouble-free creation of reliable compilers for a wide variety of target computers.

  14. Sequential Axon-derived Signals Couple Target Survival and Layer Specificity in the Drosophila Visual System

    PubMed Central

    Pecot, Matthew Y.; Chen, Yi; Akin, Orkun; Chen, Zhenqing; Tsui, C.Y. Kimberly; Zipursky, S. Lawrence

    2015-01-01

    SUMMARY Neural circuit formation relies on interactions between axons and cells within the target field. While it is well established that target-derived signals act on axons to regulate circuit assembly, the extent to which axon-derived signals control circuit formation is not known. In the Drosophila visual system, anterograde signals numerically match R1–R6 photoreceptors with their targets by controlling target proliferation and neuronal differentiation. Here we demonstrate that additional axon-derived signals selectively couple target survival with layer-specificity. We show that Jelly belly (Jeb) produced by R1–R6 axons interacts with its receptor, anaplastic lymphoma kinase (Alk), on budding dendrites to control survival of L3 neurons, one of three postsynaptic targets. L3 axons then produce Netrin, which regulates the layer-specific targeting of another neuron within the same circuit. We propose that a cascade of axon-derived signals, regulating diverse cellular processes, provides a strategy for coordinating circuit assembly across different regions of the nervous system. PMID:24742459

  15. A new liposome-based gene delivery system targeting lung epithelial cells using endothelin antagonist.

    PubMed

    Allon, Nahum; Saxena, Ashima; Chambers, Carolyn; Doctor, Bhupendra P

    2012-06-10

    We formulated a new gene delivery system based on targeted liposomes. The efficacy of the delivery system was demonstrated in in vitro and in vivo models. The targeting moiety consists of a high-affinity 7-amino-acid peptide, covalently and evenly conjugated to the liposome surface. The targeting peptide acts as an endothelin antagonist, and accelerates liposome binding and internalization. It is devoid of other biological activity. Liposomes with high phosphatidyl serine (PS) were specially formulated to help their fusion with the endosomal membrane at low pH and enable release of the liposome payload into the cytoplasm. A DNA payload, pre-compressed by protamine, was encapsulated into the liposomes, which directed the plasmid into the cell's nucleus. Upon exposure to epithelial cells, binding of the liposomes occurred within 5-10 min, followed by facilitated internalization of the complex. Endosomal escape was complete within 30 min, followed by DNA accumulation in the nucleus 2h post-transfection. A549 lung epithelial cells transfected with plasmid encoding for GFP encapsulated in targeted liposomes expressed significantly more protein than those transfected with plasmid complexed with Lipofectamine. The intra-tracheal instillation of plasmid encoding for GFP encapsulated in targeted liposomes into rat lungs resulted in the expression of GFP in bronchioles and alveoli within 5 days. These results suggest that this delivery system has great potential in targeting genes to lungs. Copyright © 2011 Elsevier B.V. All rights reserved.

  16. Experimental study of discrete diffraction behavior in a coherent atomic system

    NASA Astrophysics Data System (ADS)

    Yuan, Jinpeng; Li, Yihong; Li, Shaohua; Li, Changyong; Wang, Lirong; Xiao, Liantuan; Jia, Suotang

    2017-12-01

    Discrete diffraction behavior was experimentally studied in a coherent rubidium 5S 1/2  -  5P 3/2  -  5D 5/2 cascade system. An optical lattice was established by the interference of two coupling lasers corresponding to 5P 3/2  -  5D 5/2 transition with a small angle. The distinct discrete diffraction patterns were observed in vapor when the probe laser corresponding to the 5S 1/2  -  5P 3/2 transition propagated through the optical lattice. The optimized pertinent experimental parameters such as vapor temperature, two-photon detuning, coupling laser intensity and probe laser intensity are obtained. The experimental results are well analyzed utilizing the density-matrix theory. This system provides a new approach to investigate non-Hermitian physics and discrete solitons.

  17. Ground target geolocation based on digital elevation model for airborne wide-area reconnaissance system

    NASA Astrophysics Data System (ADS)

    Qiao, Chuan; Ding, Yalin; Xu, Yongsen; Xiu, Jihong

    2018-01-01

    To obtain the geographical position of the ground target accurately, a geolocation algorithm based on the digital elevation model (DEM) is developed for an airborne wide-area reconnaissance system. According to the platform position and attitude information measured by the airborne position and orientation system and the gimbal angles information from the encoder, the line-of-sight pointing vector in the Earth-centered Earth-fixed coordinate frame is solved by the homogeneous coordinate transformation. The target longitude and latitude can be solved with the elliptical Earth model and the global DEM. The influences of the systematic error and measurement error on ground target geolocation calculation accuracy are analyzed by the Monte Carlo method. The simulation results show that this algorithm can improve the geolocation accuracy of ground target in rough terrain area obviously. The geolocation accuracy of moving ground target can be improved by moving average filtering (MAF). The validity of the geolocation algorithm is verified by the flight test in which the plane flies at a geodetic height of 15,000 m and the outer gimbal angle is <47°. The geolocation root mean square error of the target trajectory is <45 and <7 m after MAF.

  18. An Experimental Seismic Data and Parameter Exchange System for Tsunami Warning Systems

    NASA Astrophysics Data System (ADS)

    Hoffmann, T. L.; Hanka, W.; Saul, J.; Weber, B.; Becker, J.; Heinloo, A.; Hoffmann, M.

    2009-12-01

    For several years GFZ Potsdam is operating a global earthquake monitoring system. Since the beginning of 2008, this system is also used as an experimental seismic background data center for two different regional Tsunami Warning Systems (TWS), the IOTWS (Indian Ocean) and the interim NEAMTWS (NE Atlantic and Mediterranean). The SeisComP3 (SC3) software, developed within the GITEWS (German Indian Ocean Tsunami Early Warning System) project, capable to acquire, archive and process real-time data feeds, was extended for export and import of individual processing results within the two clusters of connected SC3 systems. Therefore not only real-time waveform data are routed to the attached warning centers through GFZ but also processing results. While the current experimental NEAMTWS cluster consists of SC3 systems in six designated national warning centers in Europe, the IOTWS cluster presently includes seven centers, with another three likely to join in 2009/10. For NEAMTWS purposes, the GFZ virtual real-time seismic network (GEOFON Extended Virtual Network -GEVN) in Europe was substantially extended by adding many stations from Western European countries optimizing the station distribution. In parallel to the data collection over the Internet, a GFZ VSAT hub for secured data collection of the EuroMED GEOFON and NEAMTWS backbone network stations became operational and first data links were established through this backbone. For the Southeast Asia region, a VSAT hub has been established in Jakarta already in 2006, with some other partner networks connecting to this backbone via the Internet. Since its establishment, the experimental system has had the opportunity to prove its performance in a number of relevant earthquakes. Reliable solutions derived from a minimum of 25 stations were very promising in terms of speed. For important events, automatic alerts were released and disseminated by emails and SMS. Manually verified solutions are added as soon as they become

  19. Integrative FourD omics approach profiles the target network of the carbon storage regulatory system

    PubMed Central

    Sowa, Steven W.; Gelderman, Grant; Leistra, Abigail N.; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A.; Romeo, Tony; Baldea, Michael

    2017-01-01

    Abstract Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. PMID:28126921

  20. An analytical approach of thermodynamic behavior in a gas target system on a medical cyclotron.

    PubMed

    Jahangiri, Pouyan; Zacchia, Nicholas A; Buckley, Ken; Bénard, François; Schaffer, Paul; Martinez, D Mark; Hoehr, Cornelia

    2016-01-01

    An analytical model has been developed to study the thermo-mechanical behavior of gas targets used to produce medical isotopes, assuming that the system reaches steady-state. It is based on an integral analysis of the mass and energy balance of the gas-target system, the ideal gas law, and the deformation of the foil. The heat transfer coefficients for different target bodies and gases have been calculated. Excellent agreement is observed between experiments performed at TRIUMF's 13 MeV cyclotron and the model. Copyright © 2015 Elsevier Ltd. All rights reserved.

  1. Interferon-targeted therapy in systemic lupus erythematosus: Is this an alternative to targeting B and T cells?

    PubMed

    Kalunian, K C

    2016-09-01

    Clinical trials of investigational agents in systemic lupus erythematosus (SLE) have focused on targeting dysregulated B and T cells; however, recent translational research findings of the importance of the dysregulation of the innate immune system in SLE have led to clinical trials that target interferon. Three biologics that target type I interferons have been tested for their efficacy and safety in active SLE patients; these phase II trials have tested the hypothesis that down-regulation of interferon-regulated gene expression (the interferon signature) lessen the clinical burden of SLE. Rontalizumab, an anti-interferon-α monoclonal antibody, was studied in patients who had discontinued immunosuppressants. This study failed to show efficacy as assessed by both two outcome assessments; however, in low interferon signature patients, response was higher and corticosteroid usage was less in rontalizumab-treated patients. Sifalimumab, another anti-interferon-α monoclonal antibody, was studied in patients who remained on standard of care therapy. This study showed significantly better efficacy in patients treated with two sifalimumab dosages; significant differences were seen in the high interferon signature group. In a similar design and in a similar population as the sifalimumab study, anifrolumab, a monoclonal antibody that binds to a type I interferon receptor, was studied in patients who remained on standard of care therapy. In this study, one dosage group demonstrated efficacy and statistically significant effects were achieved in both tested dosage groups with secondary end points. Oral corticosteroid reduction to ≤7.5 mg daily was achieved in one of the tested dosage groups and organ-specific outcomes were significantly improved in that same group. For all studies, no significant differences in serious adverse effects were seen; although, herpes zoster infections were increased in sifalimumab- and anifrolumab-treated patients and influenza rates were

  2. Small-scale impacts into rock - An evaluation of the effects of target temperature on experimental results

    NASA Technical Reports Server (NTRS)

    Smrekar, S.; Cintala, M. J.; Horz, F.

    1986-01-01

    A series of cratering and catastrophic fragmentation experiments has been performed, involving the impact of aluminum and stainless-steel spheres into warm (about 298 K) and cold (about 100 K) granodiorite targets. Although some vague hints of a thermal effect might be found in some of the results, in no case was there a substantial difference between the warm and cold series. Since these experiments were well within the strength-dominated regime of impact phenomena, variations due to low target temperatures in more energetic events will probably be negligible. Thus, there appear to be no significant temperature-dependent mechanical effects during impact into solid rock over a wide range of temperatures prevalent in the solar system.

  3. Improvement of experimental testing and network training conditions with genome-wide microarrays for more accurate predictions of drug gene targets

    PubMed Central

    2014-01-01

    Background Genome-wide microarrays have been useful for predicting chemical-genetic interactions at the gene level. However, interpreting genome-wide microarray results can be overwhelming due to the vast output of gene expression data combined with off-target transcriptional responses many times induced by a drug treatment. This study demonstrates how experimental and computational methods can interact with each other, to arrive at more accurate predictions of drug-induced perturbations. We present a two-stage strategy that links microarray experimental testing and network training conditions to predict gene perturbations for a drug with a known mechanism of action in a well-studied organism. Results S. cerevisiae cells were treated with the antifungal, fluconazole, and expression profiling was conducted under different biological conditions using Affymetrix genome-wide microarrays. Transcripts were filtered with a formal network-based method, sparse simultaneous equation models and Lasso regression (SSEM-Lasso), under different network training conditions. Gene expression results were evaluated using both gene set and single gene target analyses, and the drug’s transcriptional effects were narrowed first by pathway and then by individual genes. Variables included: (i) Testing conditions – exposure time and concentration and (ii) Network training conditions – training compendium modifications. Two analyses of SSEM-Lasso output – gene set and single gene – were conducted to gain a better understanding of how SSEM-Lasso predicts perturbation targets. Conclusions This study demonstrates that genome-wide microarrays can be optimized using a two-stage strategy for a more in-depth understanding of how a cell manifests biological reactions to a drug treatment at the transcription level. Additionally, a more detailed understanding of how the statistical model, SSEM-Lasso, propagates perturbations through a network of gene regulatory interactions is achieved

  4. Application of the dynamically allocated virtual clustering management system to emulated tactical network experimentation

    NASA Astrophysics Data System (ADS)

    Marcus, Kelvin

    2014-06-01

    The U.S Army Research Laboratory (ARL) has built a "Network Science Research Lab" to support research that aims to improve their ability to analyze, predict, design, and govern complex systems that interweave the social/cognitive, information, and communication network genres. Researchers at ARL and the Network Science Collaborative Technology Alliance (NS-CTA), a collaborative research alliance funded by ARL, conducted experimentation to determine if automated network monitoring tools and task-aware agents deployed within an emulated tactical wireless network could potentially increase the retrieval of relevant data from heterogeneous distributed information nodes. ARL and NS-CTA required the capability to perform this experimentation over clusters of heterogeneous nodes with emulated wireless tactical networks where each node could contain different operating systems, application sets, and physical hardware attributes. Researchers utilized the Dynamically Allocated Virtual Clustering Management System (DAVC) to address each of the infrastructure support requirements necessary in conducting their experimentation. The DAVC is an experimentation infrastructure that provides the means to dynamically create, deploy, and manage virtual clusters of heterogeneous nodes within a cloud computing environment based upon resource utilization such as CPU load, available RAM and hard disk space. The DAVC uses 802.1Q Virtual LANs (VLANs) to prevent experimentation crosstalk and to allow for complex private networks. Clusters created by the DAVC system can be utilized for software development, experimentation, and integration with existing hardware and software. The goal of this paper is to explore how ARL and the NS-CTA leveraged the DAVC to create, deploy and manage multiple experimentation clusters to support their experimentation goals.

  5. The Unicellular Green Alga Chlamydomonas reinhardtii as an Experimental System to Study Chloroplast RNA Metabolism

    NASA Astrophysics Data System (ADS)

    Nickelsen, J.; Kück, U.

    Chloroplasts are typical organelles of photoautotrophic eukaryotic cells which drive a variety of functions, including photosynthesis. For many years the unicellular green alga Chlamydomonas reinhardtii has served as an experimental organism for studying photosynthetic processes. The recent development of molecular tools for this organism together with efficient methods of genetic analysis and the availability of many photosynthesis mutants has now made this alga a powerful model system for the analysis of chloroplast biogenesis. For example, techniques have been developed to transfer recombinant DNA into both the nuclear and the chloroplast genome. This allows both complementation tests and analyses of gene functions in vivo. Moreover, site-specific DNA recombinations in the chloroplast allow targeted gene disruption experiments which enable a "reverse genetics" to be performed. The potential of the algal system for the study of chloroplast biogenesis is illustrated in this review by the description of regulatory systems of gene expression involved in organelle biogenesis. One example concerns the regulation of trans-splicing of chloroplast mRNAs, a process which is controlled by both multiple nuclear- and chloroplast-encoded factors. The second example involves the stabilization of chloroplast mRNAs. The available data lead us predict distinct RNA elements, which interact with trans-acting factors to protect the RNA against nucleolytic attacks.

  6. Design of Student Information Management Database Application System for Office and Departmental Target Responsibility System

    NASA Astrophysics Data System (ADS)

    Zhou, Hui

    It is the inevitable outcome of higher education reform to carry out office and departmental target responsibility system, in which statistical processing of student's information is an important part of student's performance review. On the basis of the analysis of the student's evaluation, the student information management database application system is designed by using relational database management system software in this paper. In order to implement the function of student information management, the functional requirement, overall structure, data sheets and fields, data sheet Association and software codes are designed in details.

  7. New generation of oral mucosal vaccines targeting dendritic cells.

    PubMed

    Owen, Jennifer L; Sahay, Bikash; Mohamadzadeh, Mansour

    2013-12-01

    As most infectious organisms gain entry at mucosal surfaces, there is a great deal of interest in developing vaccines that elicit effective mucosal immune responses against pathogen challenge. Targeted vaccination is one of the most effective methods available to prevent and control infectious diseases. Mucosal vaccines can offer lower costs, better accessibility, needle free delivery, and a higher capacity for mass immunizations during pandemics. Both local mucosal immunity and robust systemic responses can be achieved through mucosal vaccination. Recent progress in understanding the molecular and cellular components of the mucosal immune system have allowed for the development of a novel mucosal vaccine platform utilizing specific dendritic cell-targeting peptides and orally administered lactobacilli to elicit efficient antigen specific immune responses against infections, including Bacillus anthracis in experimental models of disease. Copyright © 2013 Elsevier Ltd. All rights reserved.

  8. [sgRNA design for the CRISPR/Cas9 system and evaluation of its off-target effects].

    PubMed

    Xie, Sheng-song; Zhang, Yi; Zhang, Li-sheng; Li, Guang-lei; Zhao, Chang-zhi; Ni, Pan; Zhao, Shu-hong

    2015-11-01

    The third generation of CRISPR/Cas9-mediated genome editing technology has been successfully applied to genome modification of various species including animals, plants and microorganisms. How to improve the efficiency of CRISPR/Cas9 genome editing and reduce its off-target effects has been extensively explored in this field. Using sgRNA (Small guide RNA) with high efficiency and specificity is one of the critical factors for successful genome editing. Several software have been developed for sgRNA design and/or off-target evaluation, which have advantages and disadvantages respectively. In this review, we summarize characters of 16 kinds online and standalone software for sgRNA design and/or off-target evaluation and conduct a comparative analysis of these different kinds of software through developing 38 evaluation indexes. We also summarize 11 experimental approaches for testing genome editing efficiency and off-target effects as well as how to screen highly efficient and specific sgRNA.

  9. An analytical and experimental study of the behavior of semi-infinite metal targets under hypervelocity impact

    NASA Technical Reports Server (NTRS)

    Chakrapani, B.; Rand, J. L.

    1971-01-01

    The material strength and strain rate effects associated with the hypervelocity impact problem were considered. A yield criterion involving the second and third invariants of the stress deviator and a strain rate sensitive constitutive equation were developed. The part of total deformation which represents change in shape is attributable to the stress deviator. Constitutive equation is a means for analytically describing the mechanical response of a continuum under study. The accuracy of the yield criterion was verified utilizing the published two and three dimensional experimental data. The constants associated with the constitutive equation were determined from one dimensional quasistatic and dynamic experiments. Hypervelocity impact experiments were conducted on semi-infinite targets of 1100 aluminum, 6061 aluminum alloy, mild steel, and commercially pure lead using spherically shaped and normally incident pyrex projectiles.

  10. Lead discovery and chemical biology approaches targeting the ubiquitin proteasome system.

    PubMed

    Akinjiyan, Favour A; Carbonneau, Seth; Ross, Nathan T

    2017-10-15

    Protein degradation is critical for proteostasis, and the addition of polyubiquitin chains to a substrate is necessary for its recognition by the 26S proteasome. Therapeutic intervention in the ubiquitin proteasome system has implications ranging from cancer to neurodegeneration. Novel screening methods and chemical biology tools for targeting E1-activating, E2-conjugating and deubiquitinating enzymes will be discussed in this review. Approaches for targeting E3 ligase-substrate interactions as well as the proteasome will also be covered, with a focus on recently described approaches. Copyright © 2017. Published by Elsevier Ltd.

  11. Video camera system for locating bullet holes in targets at a ballistics tunnel

    NASA Technical Reports Server (NTRS)

    Burner, A. W.; Rummler, D. R.; Goad, W. K.

    1990-01-01

    A system consisting of a single charge coupled device (CCD) video camera, computer controlled video digitizer, and software to automate the measurement was developed to measure the location of bullet holes in targets at the International Shooters Development Fund (ISDF)/NASA Ballistics Tunnel. The camera/digitizer system is a crucial component of a highly instrumented indoor 50 meter rifle range which is being constructed to support development of wind resistant, ultra match ammunition. The system was designed to take data rapidly (10 sec between shoots) and automatically with little operator intervention. The system description, measurement concept, and procedure are presented along with laboratory tests of repeatability and bias error. The long term (1 hour) repeatability of the system was found to be 4 microns (one standard deviation) at the target and the bias error was found to be less than 50 microns. An analysis of potential errors and a technique for calibration of the system are presented.

  12. Systemic p53 gene therapy of cancer with immunolipoplexes targeted by anti-transferrin receptor scFv.

    PubMed Central

    Xu, L.; Tang, W. H.; Huang, C. C.; Alexander, W.; Xiang, L. M.; Pirollo, K. F.; Rait, A.; Chang, E. H.

    2001-01-01

    BACKGROUND: A long-standing goal in genetic therapy for cancer is a systemic gene delivery system that selectively targets tumor cells, including metastases. Here we describe a novel cationic immunolipoplex system that shows high in vivo gene transfer efficiency and anti- tumor efficacy when used for systemic p53 gene therapy of cancer. MATERIALS AND METHODS: A cationic immunolipoplex incorporating a biosynthetically lipid-tagged, anti-transferrin receptor single-chain antibody (TfRscFv), was designed to target tumor cells both in vitro and in vivo. A human breast cancer metastasis model was employed to evaluate the in vivo efficacy of systemically administered, TfRscFv-immunolipoplex-mediated, p53 gene therapy in combination with docetaxel. RESULTS: The TfRscFv-targeting cationic immunolipoplex had a size of 60-100 nm, showed enhanced tumor cell binding, and improved targeted gene delivery and transfection efficiencies, both in vitro and in vivo. The p53 tumor suppressor gene was not only systemically delivered by the immunolipoplex to human tumor xenografts in nude mice but also functionally expressed. In the nude mouse breast cancer metastasis model, the combination of the p53 gene delivered by the systemic administration of the TfRscFv-immunolipoplex and docetaxel resulted in significantly improved efficacy with prolonged survival. CONCLUSIONS: This is the first report using scFv-targeting immunolipoplexes for systemic gene therapy. The TfRscFv has a number of advantages over the transferrin (Tf) molecule itself: (1) scFv has a much smaller size than Tf producing a smaller immunolipoplex giving better penetration into solid tumors; (2) unlike Tf, the scFv is a recombinant protein, not a blood product; (3) large scale production and strict quality control of the recombinant scFv, as well as scFv-immunolipoplex, are feasible. The sensitization of tumors to chemotherapy by this tumor-targeted and efficient p53 gene delivery method could lower the effective dose of

  13. Experimental study of isolas in nonlinear systems featuring modal interactions

    PubMed Central

    Noël, Jean-Philippe; Virgin, Lawrence N.; Kerschen, Gaëtan

    2018-01-01

    The objective of the present paper is to provide experimental evidence of isolated resonances in the frequency response of nonlinear mechanical systems. More specifically, this work explores the presence of isolas, which are periodic solutions detached from the main frequency response, in the case of a nonlinear set-up consisting of two masses sliding on a horizontal guide. A careful experimental investigation of isolas is carried out using responses to swept-sine and stepped-sine excitations. The experimental findings are validated with advanced numerical simulations combining nonlinear modal analysis and bifurcation monitoring. In particular, the interactions between two nonlinear normal modes are shown to be responsible for the creation of the isolas. PMID:29584758

  14. The Advanced Linked Extended Reconnaissance & Targeting Technology Demonstration project

    NASA Astrophysics Data System (ADS)

    Edwards, Mark

    2008-04-01

    The Advanced Linked Extended Reconnaissance & Targeting (ALERT) Technology Demonstration (TD) project is addressing many operational needs of the future Canadian Army's Surveillance and Reconnaissance forces. Using the surveillance system of the Coyote reconnaissance vehicle as an experimental platform, the ALERT TD project aims to significantly enhance situational awareness by fusing multi-sensor and tactical data, developing automated processes, and integrating beyond line-of-sight sensing. The project is exploiting important advances made in computer processing capability, displays technology, digital communications, and sensor technology since the design of the original surveillance system. As the major research area within the project, concepts are discussed for displaying and fusing multi-sensor and tactical data within an Enhanced Operator Control Station (EOCS). The sensor data can originate from the Coyote's own visible-band and IR cameras, laser rangefinder, and ground-surveillance radar, as well as from beyond line-of-sight systems such as mini-UAVs and unattended ground sensors. Video-rate image processing has been developed to assist the operator to detect poorly visible targets. As a second major area of research, automatic target cueing capabilities have been added to the system. These include scene change detection, automatic target detection and aided target recognition algorithms processing both IR and visible-band images to draw the operator's attention to possible targets. The merits of incorporating scene change detection algorithms are also discussed. In the area of multi-sensor data fusion, up to Joint Defence Labs level 2 has been demonstrated. The human factors engineering aspects of the user interface in this complex environment are presented, drawing upon multiple user group sessions with military surveillance system operators. The paper concludes with Lessons Learned from the project. The ALERT system has been used in a number of C4ISR

  15. Optoelectronic System Measures Distances to Multiple Targets

    NASA Technical Reports Server (NTRS)

    Liebe, Carl Christian; Abramovici, Alexander; Bartman, Randall; Chapsky, Jacob; Schmalz, John; Coste, Keith; Litty, Edward; Lam, Raymond; Jerebets, Sergei

    2007-01-01

    An optoelectronic metrology apparatus now at the laboratory-prototype stage of development is intended to repeatedly determine distances of as much as several hundred meters, at submillimeter accuracy, to multiple targets in rapid succession. The underlying concept of optoelectronic apparatuses that can measure distances to targets is not new; such apparatuses are commonly used in general surveying and machining. However, until now such apparatuses have been, variously, constrained to (1) a single target or (2) multiple targets with a low update rate and a requirement for some a priori knowledge of target geometry. When fully developed, the present apparatus would enable measurement of distances to more than 50 targets at an update rate greater than 10 Hz, without a requirement for a priori knowledge of target geometry. The apparatus (see figure) includes a laser ranging unit (LRU) that includes an electronic camera (photo receiver), the field of view of which contains all relevant targets. Each target, mounted at a fiducial position on an object of interest, consists of a small lens at the output end of an optical fiber that extends from the object of interest back to the LRU. For each target and its optical fiber, there is a dedicated laser that is used to illuminate the target via the optical fiber. The targets are illuminated, one at a time, with laser light that is modulated at a frequency of 10.01 MHz. The modulated laser light is emitted by the target, from where it returns to the camera (photodetector), where it is detected. Both the outgoing and incoming 10.01-MHz laser signals are mixed with a 10-MHz local-oscillator to obtain beat notes at 10 kHz, and the difference between the phases of the beat notes is measured by a phase meter. This phase difference serves as a measure of the total length of the path traveled by light going out through the optical fiber and returning to the camera (photodetector) through free space. Because the portion of the path

  16. Experimental results for a prototype 3-D acoustic imaging system using an ultra-sparse planar array

    NASA Astrophysics Data System (ADS)

    Impagliazzo, John M.; Chiang, Alice M.; Broadstone, Steven R.

    2002-11-01

    A handheld high resolution sonar has been under development to provide Navy Divers with a 3-D acoustic imaging system for mine reconnaissance. An ultra-sparse planar array, consisting of 121 1 mm x1 mm, 2 MHz elements, was fabricated to provide 3-D acoustic images. The array was 10 cm x10 cm. A full array at this frequency with elements at half-wavelength spacing would consist of 16384 elements. The first phase of testing of the planar array was completed in September 2001 with the characterization of the array in the NUWC Acoustic Test Facility (ATF). The center frequency was 2 MHz with a 667 kHz bandwidth. A system-level technology demonstration will be conducted in July 2002 with a real-time beamformer and near real-time 3-D imaging software. The demonstration phase consists of imaging simple targets at a range of 3 m in the ATF. Experimental results obtained will be reported on. [Work supported by the Defense Applied Research Project Agency, Advance Technology Office, Dr. Theo Kooij, Program Manager.

  17. Brain-inspired cheminformatics of drug-target brain interactome, synthesis, and assay of TVP1022 derivatives.

    PubMed

    Romero-Durán, Francisco J; Alonso, Nerea; Yañez, Matilde; Caamaño, Olga; García-Mera, Xerardo; González-Díaz, Humberto

    2016-04-01

    The use of Cheminformatics tools is gaining importance in the field of translational research from Medicinal Chemistry to Neuropharmacology. In particular, we need it for the analysis of chemical information on large datasets of bioactive compounds. These compounds form large multi-target complex networks (drug-target interactome network) resulting in a very challenging data analysis problem. Artificial Neural Network (ANN) algorithms may help us predict the interactions of drugs and targets in CNS interactome. In this work, we trained different ANN models able to predict a large number of drug-target interactions. These models predict a dataset of thousands of interactions of central nervous system (CNS) drugs characterized by > 30 different experimental measures in >400 different experimental protocols for >150 molecular and cellular targets present in 11 different organisms (including human). The model was able to classify cases of non-interacting vs. interacting drug-target pairs with satisfactory performance. A second aim focus on two main directions: the synthesis and assay of new derivatives of TVP1022 (S-analogues of rasagiline) and the comparison with other rasagiline derivatives recently reported. Finally, we used the best of our models to predict drug-target interactions for the best new synthesized compound against a large number of CNS protein targets. Copyright © 2015 Elsevier Ltd. All rights reserved.

  18. Research on the underwater target imaging based on the streak tube laser lidar

    NASA Astrophysics Data System (ADS)

    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.

  19. A system for the real-time display of radar and video images of targets

    NASA Technical Reports Server (NTRS)

    Allen, W. W.; Burnside, W. D.

    1990-01-01

    Described here is a software and hardware system for the real-time display of radar and video images for use in a measurement range. The main purpose is to give the reader a clear idea of the software and hardware design and its functions. This system is designed around a Tektronix XD88-30 graphics workstation, used to display radar images superimposed on video images of the actual target. The system's purpose is to provide a platform for tha analysis and documentation of radar images and their associated targets in a menu-driven, user oriented environment.

  20. Pathogenic Inflammation and Its Therapeutic Targeting in Systemic Lupus Erythematosus

    PubMed Central

    Gottschalk, Timothy A.; Tsantikos, Evelyn; Hibbs, Margaret L.

    2015-01-01

    Systemic lupus erythematosus (SLE, lupus) is a highly complex and heterogeneous autoimmune disease that most often afflicts women in their child-bearing years. It is characterized by circulating self-reactive antibodies that deposit in tissues, including skin, kidneys, and brain, and the ensuing inflammatory response can lead to irreparable tissue damage. Over many years, clinical trials in SLE have focused on agents that control B- and T-lymphocyte activation, and, with the single exception of an agent known as belimumab which targets the B-cell survival factor BAFF, they have been disappointing. At present, standard therapy for SLE with mild disease is the agent hydroxychloroquine. During disease flares, steroids are often used, while the more severe manifestations with major organ involvement warrant potent, broad-spectrum immunosuppression with cyclophosphamide or mycophenolate. Current treatments have severe and dose-limiting toxicities and thus a more specific therapy targeting a causative factor or signaling pathway would be greatly beneficial in SLE treatment. Moreover, the ability to control inflammation alongside B-cell activation may be a superior approach for disease control. There has been a recent focus on the innate immune system and associated inflammation, which has uncovered key players in driving the pathogenesis of SLE. Delineating some of these intricate inflammatory mechanisms has been possible with studies using spontaneous mouse mutants and genetically engineered mice. These strains, to varying degrees, exhibit hallmarks of the human disease and therefore have been utilized to model human SLE and to test new drugs. Developing a better understanding of the initiation and perpetuation of disease in SLE may uncover suitable novel targets for therapeutic intervention. Here, we discuss the involvement of inflammation in SLE disease pathogenesis, with a focus on several key proinflammatory cytokines and myeloid growth factors, and review the known

  1. Dual systemic tumor targeting with ligand-directed phage and Grp78 promoter induces tumor regression.

    PubMed

    Kia, Azadeh; Przystal, Justyna M; Nianiaris, Nastasia; Mazarakis, Nicholas D; Mintz, Paul J; Hajitou, Amin

    2012-12-01

    The tumor-specific Grp78 promoter is overexpressed in aggressive tumors. Cancer patients would benefit greatly from application of this promoter in gene therapy and molecular imaging; however, clinical benefit is limited by lack of strategies to target the systemic delivery of Grp78-driven transgenes to tumors. This study aims to assess the systemic efficacy of Grp78-guided expression of therapeutic and imaging transgenes relative to the standard cytomegalovirus (CMV) promoter. Combination of ligand and Grp78 transcriptional targeting into a single vector would facilitate systemic applications of the Grp78 promoter. We generated a dual tumor-targeted phage containing the arginine-glycine-aspartic acid tumor homing ligand and Grp78 promoter. Next, we combined flow cytometry, Western blot analysis, bioluminescence imaging of luciferase, and HSVtk/ganciclovir gene therapy and compared efficacy to conventional phage carrying the CMV promoter in vitro and in vivo in subcutaneous models of rat and human glioblastoma. We show that double-targeted phage provides persistent transgene expression in vitro and in tumors in vivo after systemic administration compared with conventional phage. Next, we showed significant tumor killing in vivo using the HSVtk/ganciclovir gene therapy and found a systemic antitumor effect of Grp78-driven HSVtk against therapy-resistant tumors. Finally, we uncovered a novel mechanism of Grp78 promoter activation whereby HSVtk/ganciclovir therapy upregulates Grp78 and transgene expression via the conserved unfolded protein response signaling cascade. These data validate the potential of Grp78 promoter in systemic cancer gene therapy and report the efficacy of a dual tumor targeting phage that may prove useful for translation into gene therapy and molecular imaging applications.

  2. Numerical-experimental study of internal fixation system "Dufoo" for vertebral fractures.

    PubMed

    Nieto-Miranda, J Jesús; Faraón-Carbajal Romero, Manuel; Sánchez-Aguilar, Jons

    2012-01-01

    We describe a numerical experimental study of the stress generated by the internal fixation system "Dufoo" used in the treatment of vertebral fractures with the purpose of validating the numerical model of human lumbar vertebrae under the main physiological loads that the human body is exposed to in this area. The objective is to model and numerically simulate the elements of the musculoskeletal system to collect the stresses generated and other parameters that are difficult to measure experimentally in the thoracic lumbar vertebrae. We used an internal fixator "Dufoo" and vertebrae L2-L3-L4 specimens from pig and human. The system uses a total L3 corpectomy. The fixator acts as a mechanical bridge implant from L2 to L4. Numerical analysis was performed using the finite element method (FEM). For the experimental study, reflective photoelasticity and extensometry were used. Torsion and combined loads generate the main displacements and stresses in the study system, determining that the internal fixation carries out part of the function of the damaged organ structure when absorbing the stresses presented by applied loads. Numerical analysis allows great freedom in the management of the variables involved in the developed models using radiological images. Geometric models are obtained and are entered into FEM programs that allow testing using parameters that, under actual conditions, may not be easily carried out, allowing to comprehensively determine the biomechanical behavior of the coupled system of study.

  3. [Study on liver targeted drug delivery system of the effective anticancer component from Bolbstemma paniculatum].

    PubMed

    Sun, Yi-Yi; Ll, Tong-Hui; Tang, Chen-Kang; Zhu, Zi-Ping; Chi, Qun; Hou, Shi-Xiang

    2005-06-01

    To study the liver targeted drug delivery system of TBMS--the effective anticancer component from Bolbstemma paniculatum, and to discuss the system's function of decreasing toxicity. BCA was used as carrier material. The preparation through overall feedback dynamic techniques. The properties of preparation and toxicology were also technology of nanoparticles was optimized studied. Thenanoparticles' targeting in mice vivo was observed with transmission electron microscopy. The function of decreasing toxicity was researched by the XXTX-2000 automatic quantitative analysis management system. D50 was 0.68 microm. Drug-loading rate and entrapment rate were 37.3% and 88.6% respectively. The release in vitro accorded with Weibull equation. The reaching release balance time and the t 1/2 extended 26 times and 19 times respectively comparing with injection. Nanoparticles mainly distributed in liver tissue. Their toxicity to lung and liver was evidently lower than injection. Nanoparticles' LD50 exceeded injection's by 13.5% and their stimulus was much lower than injection. The TBMS can be targeted to liver by liver targeted drug delivery system. At the same time, the problem about the toxicity hindering clinical application could be solved, which lays the foundation for the further studies on TBMS.

  4. Unimpaired Autoreactive T-Cell Traffic Within the Central Nervous System During Tumor Necrosis Factor Receptor-Mediated inhibition of Experimental Autoimmune Encephalomyelitis

    NASA Astrophysics Data System (ADS)

    Korner, Heinrich; Goodsall, Anna L.; Lemckert, Frances A.; Scallon, Bernard J.; Ghrayeb, John; Ford, Andrew L.; Sedgwick, Jonathon D.

    1995-11-01

    The critical role of tumor necrosis factor (TNF) as a mediator in autoimmune inflammatory processes is evident from in vivo studies with TNF-blocking agents. However, the mechanisms by which TNF, and possibly also its homologue lymphotoxin α, contributes to development of pathology in rheumatoid arthritis and Crohn disease and in animal models like experimental autoimmune encephalomyelitis is unclear. Possibilities include regulation of vascular adhesion molecules enabling leukocyte movement into tissues or direct cytokine-mediated effector functions such as mediation of tissue damage. Here we show that administration of a TNF receptor (55 kDa)-IgG fusion protein prevented clinical signs of actively induced experimental autoimmune encephalomyelitis. Significantly, the total number of CD4^+ T lymphocytes isolated from the central nervous system of clinically healthy treated versus diseased control animals was comparable. By using a CD45 congenic model of passively transferred experimental autoimmune encephalomyelitis to enable tracking of myelin basic protein-specific effector T lymphocytes, prevention of clinical signs of disease was again demonstrated in treated animals but without quantitative or qualitative impediment to the movement of autoreactive T lymphocytes to and within the central nervous system. Thus, despite the uninterrupted movement of specific T lymphocytes into the target tissue, subsequent disease development was blocked. This provides compelling evidence for a direct effector role of TNF/lymphotoxin α in autoimmune tissue damage.

  5. Integrative FourD omics approach profiles the target network of the carbon storage regulatory system.

    PubMed

    Sowa, Steven W; Gelderman, Grant; Leistra, Abigail N; Buvanendiran, Aishwarya; Lipp, Sarah; Pitaktong, Areen; Vakulskas, Christopher A; Romeo, Tony; Baldea, Michael; Contreras, Lydia M

    2017-02-28

    Multi-target regulators represent a largely untapped area for metabolic engineering and anti-bacterial development. These regulators are complex to characterize because they often act at multiple levels, affecting proteins, transcripts and metabolites. Therefore, single omics experiments cannot profile their underlying targets and mechanisms. In this work, we used an Integrative FourD omics approach (INFO) that consists of collecting and analyzing systems data throughout multiple time points, using multiple genetic backgrounds, and multiple omics approaches (transcriptomics, proteomics and high throughput sequencing crosslinking immunoprecipitation) to evaluate simultaneous changes in gene expression after imposing an environmental stress that accentuates the regulatory features of a network. Using this approach, we profiled the targets and potential regulatory mechanisms of a global regulatory system, the well-studied carbon storage regulatory (Csr) system of Escherichia coli, which is widespread among bacteria. Using 126 sets of proteomics and transcriptomics data, we identified 136 potential direct CsrA targets, including 50 novel ones, categorized their behaviors into distinct regulatory patterns, and performed in vivo fluorescence-based follow up experiments. The results of this work validate 17 novel mRNAs as authentic direct CsrA targets and demonstrate a generalizable strategy to integrate multiple lines of omics data to identify a core pool of regulator targets. © The Author(s) 2017. Published by Oxford University Press on behalf of Nucleic Acids Research.

  6. Development of a systematic feedback isolation approach for targeted strains from mixed culture systems.

    PubMed

    Poudel, Pramod; Tashiro, Yukihiro; Miyamoto, Hirokuni; Miyamoto, Hisashi; Okugawa, Yuki; Sakai, Kenji

    2017-01-01

    Elucidation of functions of bacteria in a mixed culture system (MCS) such as composting, activated sludge system is difficult, since the system is complicating with many unisolated bacteria. Here, we developed a systematic feedback isolation strategy for the isolation and rapid screening of multiple targeted strains from MCS. Six major strains (Corynebacterium sphenisci, Bacillus thermocloacae, Bacillus thermoamylovorans, Bacillus smithii, Bacillus humi, and Bacillus coagulans), which are detected by denaturing gradient gel electrophoresis (DGGE) analysis in our previous study on MCS for l-lactic acid production, were targeted for isolation. Based on information of suitable cultivation conditions (e.g., media, pH, temperature) from the literature, feedback isolation was performed to form 136 colonies. The following direct colony matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) was optimised as the second screening to narrow down 20 candidate colonies from similar spectra patterns with six closest type strains. This step could distinguish bacteria at the species level with distance similarity scores ≥0.55 corresponding to 16S rRNA gene sequence similarity ≥98.2%, suggesting that this is an effective technique to minimize isolates close to targeted type strains. Analysis of 16S rRNA gene sequences indicated that two targeted strains and one strain related to the target had successfully been isolated, showing high similarities (99.5-100%) with the sequences from the DGGE bands, and that the other candidates were affiliated with three strains that were closely related to the target species. This study proposes a new method for systematic feedback isolation that may be useful for isolating targeted strains from MCS for further investigation. Copyright © 2016 The Society for Biotechnology, Japan. Published by Elsevier B.V. All rights reserved.

  7. Research on target information optics communications transmission characteristic and performance in multi-screens testing system

    NASA Astrophysics Data System (ADS)

    Li, Hanshan

    2016-04-01

    To enhance the stability and reliability of multi-screens testing system, this paper studies multi-screens target optical information transmission link properties and performance in long-distance, sets up the discrete multi-tone modulation transmission model based on geometric model of laser multi-screens testing system and visible light information communication principle; analyzes the electro-optic and photoelectric conversion function of sender and receiver in target optical information communication system; researches target information transmission performance and transfer function of the generalized visible-light communication channel; found optical information communication transmission link light intensity space distribution model and distribution function; derives the SNR model of information transmission communication system. Through the calculation and experiment analysis, the results show that the transmission error rate increases with the increment of transmission rate in a certain channel modulation depth; when selecting the appropriate transmission rate, the bit error rate reach 0.01.

  8. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy

    PubMed Central

    Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J

    2017-01-01

    A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. PMID:28193698

  9. The innate and adaptive infiltrating immune systems as targets for breast cancer immunotherapy.

    PubMed

    Law, Andrew M K; Lim, Elgene; Ormandy, Christopher J; Gallego-Ortega, David

    2017-04-01

    A cancer cell-centric view has long dominated the field of cancer biology. Research efforts have focussed on aberrant cancer cell signalling pathways and on changes to cancer cell DNA. Mounting evidence demonstrates that many cancer-associated cell types within the tumour stroma co-evolve and support tumour growth and development, greatly modifying cancer cell behaviour, facilitating invasion and metastasis and controlling dormancy and sensitivity to drug therapy. Thus, these stromal cells represent potential targets for cancer therapy. Among these cell types, immune cells have emerged as a promising target for therapy. The adaptive and the innate immune system play an important role in normal mammary development and breast cancer. The number of infiltrating adaptive immune system cells with tumour-rejecting capacity, primarily, T lymphocytes, is lower in breast cancer compared with other cancer types, but infiltration occurs in a large proportion of cases. There is strong evidence demonstrating the importance of the immunosuppressive role of the innate immune system during breast cancer progression. A consideration of components of both the innate and the adaptive immune system is essential for the design and development of immunotherapies in breast cancer. In this review, we focus on the importance of immunosuppressive myeloid-derived suppressor cells (MDSCs) as potential targets for breast cancer therapy. © 2017 The authors.

  10. An innovative pre-targeting strategy for tumor cell specific imaging and therapy

    NASA Astrophysics Data System (ADS)

    Qin, Si-Yong; Peng, Meng-Yun; Rong, Lei; Jia, Hui-Zhen; Chen, Si; Cheng, Si-Xue; Feng, Jun; Zhang, Xian-Zheng

    2015-08-01

    A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging and therapeutic agents for tumor treatments.A programmed pre-targeting system for tumor cell imaging and targeting therapy was established based on the ``biotin-avidin'' interaction. In this programmed functional system, transferrin-biotin can be actively captured by tumor cells with the overexpression of transferrin receptors, thus achieving the pre-targeting modality. Depending upon avidin-biotin recognition, the attachment of multivalent FITC-avidin to biotinylated tumor cells not only offered the rapid fluorescence labelling, but also endowed the pre-targeted cells with targeting sites for the specifically designed biotinylated peptide nano-drug. Owing to the successful pre-targeting, tumorous HepG2 and HeLa cells were effectively distinguished from the normal 3T3 cells via fluorescence imaging. In addition, the self-assembled peptide nano-drug resulted in enhanced cell apoptosis in the observed HepG2 cells. The tumor cell specific pre-targeting strategy is applicable for a variety of different imaging

  11. Blueprint for antimicrobial hit discovery targeting metabolic networks.

    PubMed

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

    2010-01-19

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

  12. Experimental Demonstration of In-Place Calibration for Time Domain Microwave Imaging System

    NASA Astrophysics Data System (ADS)

    Kwon, S.; Son, S.; Lee, K.

    2018-04-01

    In this study, the experimental demonstration of in-place calibration was conducted using the developed time domain measurement system. Experiments were conducted using three calibration methods—in-place calibration and two existing calibrations, that is, array rotation and differential calibration. The in-place calibration uses dual receivers located at an equal distance from the transmitter. The received signals at the dual receivers contain similar unwanted signals, that is, the directly received signal and antenna coupling. In contrast to the simulations, the antennas are not perfectly matched and there might be unexpected environmental errors. Thus, we experimented with the developed experimental system to demonstrate the proposed method. The possible problems with low signal-to-noise ratio and clock jitter, which may exist in time domain systems, were rectified by averaging repeatedly measured signals. The tumor was successfully detected using the three calibration methods according to the experimental results. The cross correlation was calculated using the reconstructed image of the ideal differential calibration for a quantitative comparison between the existing rotation calibration and the proposed in-place calibration. The mean value of cross correlation between the in-place calibration and ideal differential calibration was 0.80, and the mean value of cross correlation of the rotation calibration was 0.55. Furthermore, the results of simulation were compared with the experimental results to verify the in-place calibration method. A quantitative analysis was also performed, and the experimental results show a tendency similar to the simulation.

  13. Targeted Cellular Drug Delivery using Tailored Dendritic Nanostructures

    NASA Astrophysics Data System (ADS)

    Kannan, Rangaramanujam; Kolhe, Parag; Kannan, Sujatha; Lieh-Lai, Mary

    2002-03-01

    Dendrimers and hyperbranched polymers possess highly branched architectures, with a large number of controllable, tailorble, ‘peripheral’ functionalities. Since the surface chemistry of these materials can be modified with relative ease, these materials have tremendous potential in targeted drug and gene delivery. The large number of end groups can also be tailored to create special affinity to targeted cells, and can also encapsulate drugs and deliver them in a controlled manner. We are developing tailor-modified dendritic systems for drug delivery. Synthesis, in-vitro drug loading, in-vitro drug delivery, and the targeting efficiency to the cell are being studied systematically using a wide variety of experimental tools. Polyamidoamine and Polyol dendrimers, with different generations and end-groups are studied, with drugs such as Ibuprofen and Methotrexate. Our results indicate that a large number of drug molecules can be encapsulated/attached to the dendrimers, depending on the end groups. The drug-encapsulated dendrimer is able to enter the cells rapidly and deliver the drug. Targeting strategies being explored

  14. An affinity-directed protein missile system for targeted proteolysis.

    PubMed

    Fulcher, Luke J; Macartney, Thomas; Bozatzi, Polyxeni; Hornberger, Annika; Rojas-Fernandez, Alejandro; Sapkota, Gopal P

    2016-10-01

    The von Hippel-Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha (HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and degradation through the proteasome. In this report, we modify VHL to engineer an affinity-directed protein missile (AdPROM) system to direct specific endogenous target proteins for proteolysis in mammalian cells. The proteolytic AdPROM construct harbours a cameloid anti-green fluorescence protein (aGFP) nanobody that is fused to VHL for either constitutive or tetracycline-inducible expression. For target proteins, we exploit CRISPR/Cas9 to rapidly generate human kidney HEK293 and U2OS osteosarcoma homozygous knock-in cells harbouring GFP tags at the VPS34 (vacuolar protein sorting 34) and protein associated with SMAD1 (PAWS1, aka FAM83G) loci, respectively. Using these cells, we demonstrate that the expression of the VHL-aGFP AdPROM system results in near-complete degradation of the endogenous GFP-VPS34 and PAWS1-GFP proteins through the proteasome. Additionally, we show that Tet-inducible destruction of GFP-VPS34 results in the degradation of its associated partner, UVRAG, and reduction in levels of cellular phosphatidylinositol 3-phosphate. © 2016 The Authors.

  15. An affinity-directed protein missile system for targeted proteolysis

    PubMed Central

    Fulcher, Luke J.; Macartney, Thomas; Bozatzi, Polyxeni; Hornberger, Annika; Rojas-Fernandez, Alejandro

    2016-01-01

    The von Hippel–Lindau (VHL) protein serves to recruit the hypoxia-inducible factor alpha (HIF1α) protein under normoxia to the CUL2 E3 ubiquitin ligase for its ubiquitylation and degradation through the proteasome. In this report, we modify VHL to engineer an affinity-directed protein missile (AdPROM) system to direct specific endogenous target proteins for proteolysis in mammalian cells. The proteolytic AdPROM construct harbours a cameloid anti-green fluorescence protein (aGFP) nanobody that is fused to VHL for either constitutive or tetracycline-inducible expression. For target proteins, we exploit CRISPR/Cas9 to rapidly generate human kidney HEK293 and U2OS osteosarcoma homozygous knock-in cells harbouring GFP tags at the VPS34 (vacuolar protein sorting 34) and protein associated with SMAD1 (PAWS1, aka FAM83G) loci, respectively. Using these cells, we demonstrate that the expression of the VHL-aGFP AdPROM system results in near-complete degradation of the endogenous GFP-VPS34 and PAWS1-GFP proteins through the proteasome. Additionally, we show that Tet-inducible destruction of GFP-VPS34 results in the degradation of its associated partner, UVRAG, and reduction in levels of cellular phosphatidylinositol 3-phosphate. PMID:27784791

  16. Model Selection in Systems Biology Depends on Experimental Design

    PubMed Central

    Silk, Daniel; Kirk, Paul D. W.; Barnes, Chris P.; Toni, Tina; Stumpf, Michael P. H.

    2014-01-01

    Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis. PMID:24922483

  17. Model selection in systems biology depends on experimental design.

    PubMed

    Silk, Daniel; Kirk, Paul D W; Barnes, Chris P; Toni, Tina; Stumpf, Michael P H

    2014-06-01

    Experimental design attempts to maximise the information available for modelling tasks. An optimal experiment allows the inferred models or parameters to be chosen with the highest expected degree of confidence. If the true system is faithfully reproduced by one of the models, the merit of this approach is clear - we simply wish to identify it and the true parameters with the most certainty. However, in the more realistic situation where all models are incorrect or incomplete, the interpretation of model selection outcomes and the role of experimental design needs to be examined more carefully. Using a novel experimental design and model selection framework for stochastic state-space models, we perform high-throughput in-silico analyses on families of gene regulatory cascade models, to show that the selected model can depend on the experiment performed. We observe that experimental design thus makes confidence a criterion for model choice, but that this does not necessarily correlate with a model's predictive power or correctness. Finally, in the special case of linear ordinary differential equation (ODE) models, we explore how wrong a model has to be before it influences the conclusions of a model selection analysis.

  18. Target depth dependence of damage rate in metals by 150 MeV proton irradiation

    NASA Astrophysics Data System (ADS)

    Yoshiie, T.; Ishi, Y.; Kuriyama, Y.; Mori, Y.; Sato, K.; Uesugi, T.; Xu, Q.

    2015-01-01

    A series of irradiation experiments with 150 MeV protons was performed. The relationship between target depth (or shield thickness) and displacement damage during proton irradiation was obtained by in situ electrical resistance measurements at 20 K. Positron annihilation lifetime measurements were also performed at room temperature after irradiation, as a function of the target thickness. The displacement damage was found to be high close to the beam incident surface area, and decreased with increasing target depth. The experimental results were compared with damage production calculated with an advanced Monte Carlo particle transport code system (PHITS).

  19. Experimental determination of particle range and dose distribution in thick targets through fragmentation reactions of stable heavy ions.

    PubMed

    Inaniwa, Taku; Kohno, Toshiyuki; Tomitani, Takehiro; Urakabe, Eriko; Sato, Shinji; Kanazawa, Mitsutaka; Kanai, Tatsuaki

    2006-09-07

    In radiation therapy with highly energetic heavy ions, the conformal irradiation of a tumour can be achieved by using their advantageous features such as the good dose localization and the high relative biological effectiveness around their mean range. For effective utilization of such properties, it is necessary to evaluate the range of incident ions and the deposited dose distribution in a patient's body. Several methods have been proposed to derive such physical quantities; one of them uses positron emitters generated through projectile fragmentation reactions of incident ions with target nuclei. We have proposed the application of the maximum likelihood estimation (MLE) method to a detected annihilation gamma-ray distribution for determination of the range of incident ions in a target and we have demonstrated the effectiveness of the method with computer simulations. In this paper, a water, a polyethylene and a polymethyl methacrylate target were each irradiated with stable (12)C, (14)N, (16)O and (20)Ne beams. Except for a few combinations of incident beams and targets, the MLE method could determine the range of incident ions R(MLE) with a difference between R(MLE) and the experimental range of less than 2.0 mm under the circumstance that the measurement of annihilation gamma rays was started just after the irradiation of 61.4 s and lasted for 500 s. In the process of evaluating the range of incident ions with the MLE method, we must calculate many physical quantities such as the fluence and the energy of both primary ions and fragments as a function of depth in a target. Consequently, by using them we can obtain the dose distribution. Thus, when the mean range of incident ions is determined with the MLE method, the annihilation gamma-ray distribution and the deposited dose distribution can be derived simultaneously. The derived dose distributions in water for the mono-energetic heavy-ion beams of four species were compared with those measured with an

  20. Particle production of a graphite target system for the intensity frontier

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

    Ding, X.; Kirk, H.; McDonald, K. T.

    2015-05-03

    A solid graphite target system is considered for an intense muon and/or neutrino source in support of physics at the intensity frontier. We previously optimized the geometric parameters of the beam and target to maximize particle production at low energies by incoming protons with kinetic energy of 6.75 GeV and an rms geometric emittance of 5 mm-mrad using the MARS15(2014) code. In this study, we ran MARS15 with ROOT-based geometry and also considered a mercury-jet target as an upgrade option. The optimization was extended to focused proton beams with transverse emittances from 5 to 50 mm-mrad, showing that the particlemore » production decreases slowly with increasing emittance. We also studied beam-dump configurations to suppress the rate of undesirable high-energy secondary particles in the beam.« less

  1. Advances in oral nano-delivery systems for colon targeted drug delivery in inflammatory bowel disease: selective targeting to diseased versus healthy tissue.

    PubMed

    Hua, Susan; Marks, Ellen; Schneider, Jennifer J; Keely, Simon

    2015-07-01

    Colon targeted drug delivery is an active area of research for local diseases affecting the colon, as it improves the efficacy of therapeutics and enables localized treatment, which reduces systemic toxicity. Targeted delivery of therapeutics to the colon is particularly advantageous for the treatment of inflammatory bowel disease (IBD), which includes ulcerative colitis and Crohn's disease. Advances in oral drug delivery design have significantly improved the bioavailability of drugs to the colon; however in order for a drug to have therapeutic efficacy during disease, considerations must be made for the altered physiology of the gastrointestinal (GI) tract that is associated with GI inflammation. Nanotechnology has been used in oral dosage formulation design as strategies to further enhance uptake into diseased tissue within the colon. This review will describe some of the physiological challenges faced by orally administered delivery systems in IBD, the important developments in orally administered nano-delivery systems for colon targeting, and the future advances of this research. Inflammatory Bowel Disease (IBD) poses a significant problem for a large number of patients worldwide. Current medical therapy mostly aims at suppressing the active inflammatory episodes. In this review article, the authors described and discussed the various approaches current nano-delivery systems can offer in overcoming the limitations of conventional drug formulations. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  2. Preliminary experimental results from a MARS Micro-CT system.

    PubMed

    He, Peng; Yu, Hengyong; Thayer, Patrick; Jin, Xin; Xu, Qiong; Bennett, James; Tappenden, Rachael; Wei, Biao; Goldstein, Aaron; Renaud, Peter; Butler, Anthony; Butler, Phillip; Wang, Ge

    2012-01-01

    The Medipix All Resolution System (MARS) system is a commercial spectral/multi-energy micro-CT scanner designed and assembled by the MARS Bioimaging, Ltd. in New Zealand. This system utilizes the state-of-the-art Medipix photon-counting, energy-discriminating detector technology developed by a collaboration at European Organization for Nuclear Research (CERN). In this paper, we report our preliminary experimental results using this system, including geometrical alignment, photon energy characterization, protocol optimization, and spectral image reconstruction. We produced our scan datasets with a multi-material phantom, and then applied ordered subset-simultaneous algebraic reconstruction technique (OS-SART) to reconstruct images in different energy ranges and principal component analysis (PCA) to evaluate spectral deviation among the energy ranges.

  3. Real-Time Implementation of an Asynchronous Vision-Based Target Tracking System for an Unmanned Aerial Vehicle

    DTIC Science & Technology

    2007-06-01

    Chin Khoon Quek. “Vision Based Control and Target Range Estimation for Small Unmanned Aerial Vehicle.” Master’s Thesis, Naval Postgraduate School...December 2005. [6] Kwee Chye Yap. “Incorporating Target Mensuration System for Target Motion Estimation Along a Road Using Asynchronous Filter

  4. In vivo potency revisited - Keep the target in sight.

    PubMed

    Gabrielsson, Johan; Peletier, Lambertus A; Hjorth, Stephan

    2018-04-01

    Potency is a central parameter in pharmacological and biochemical sciences, as well as in drug discovery and development endeavors. It is however typically defined in terms only of ligand to target binding affinity also in in vivo experimentation, thus in a manner analogous to in in vitro studies. As in vivo potency is in fact a conglomerate of events involving ligand, target, and target-ligand complex processes, overlooking some of the fundamental differences between in vivo and in vitro may result in serious mispredictions of in vivo efficacious dose and exposure. The analysis presented in this paper compares potency measures derived from three model situations. Model A represents the closed in vitro system, defining target binding of a ligand when total target and ligand concentrations remain static and constant. Model B describes an open in vivo system with ligand input and clearance (Cl (L) ), adding in parallel to the turnover (k syn , k deg ) of the target. Model C further adds to the open in vivo system in Model B also the elimination of the target-ligand complex (k e(RL) ) via a first-order process. We formulate corresponding equations of the equilibrium (steady-state) relationships between target and ligand, and complex and ligand for each of the three model systems and graphically illustrate the resulting simulations. These equilibrium relationships demonstrate the relative impact of target and target-ligand complex turnover, and are easier to interpret than the more commonly used ligand-, target- and complex concentration-time courses. A new potency expression, labeled L 50 , is then derived. L 50 is the ligand concentration at half-maximal target and complex concentrations and is an amalgamation of target turnover, target-ligand binding and complex elimination parameters estimated from concentration-time data. L 50 is then compared to the dissociation constant K d (target-ligand binding affinity), the conventional Black & Leff potency estimate EC 50

  5. Prediction of miRNA targets.

    PubMed

    Oulas, Anastasis; Karathanasis, Nestoras; Louloupi, Annita; Pavlopoulos, Georgios A; Poirazi, Panayiota; Kalantidis, Kriton; Iliopoulos, Ioannis

    2015-01-01

    Computational methods for miRNA target prediction are currently undergoing extensive review and evaluation. There is still a great need for improvement of these tools and bioinformatics approaches are looking towards high-throughput experiments in order to validate predictions. The combination of large-scale techniques with computational tools will not only provide greater credence to computational predictions but also lead to the better understanding of specific biological questions. Current miRNA target prediction tools utilize probabilistic learning algorithms, machine learning methods and even empirical biologically defined rules in order to build models based on experimentally verified miRNA targets. Large-scale protein downregulation assays and next-generation sequencing (NGS) are now being used to validate methodologies and compare the performance of existing tools. Tools that exhibit greater correlation between computational predictions and protein downregulation or RNA downregulation are considered the state of the art. Moreover, efficiency in prediction of miRNA targets that are concurrently verified experimentally provides additional validity to computational predictions and further highlights the competitive advantage of specific tools and their efficacy in extracting biologically significant results. In this review paper, we discuss the computational methods for miRNA target prediction and provide a detailed comparison of methodologies and features utilized by each specific tool. Moreover, we provide an overview of current state-of-the-art high-throughput methods used in miRNA target prediction.

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

    PubMed

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

    2016-12-01

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

  7. Experimental study of 38Ar+α reaction cross sections relevant to the 41Ca abundance in the solar system

    NASA Astrophysics Data System (ADS)

    Talwar, R.; Bojazi, M. J.; Mohr, P.; Auranen, K.; Avila, M. L.; Ayangeakaa, A. D.; Harker, J.; Hoffman, C. R.; Jiang, C. L.; Kuvin, S. A.; Meyer, B. S.; Rehm, K. E.; Santiago-Gonzalez, D.; Sethi, J.; Ugalde, C.; Winkelbauer, J. R.

    2018-05-01

    In massive stars, the 41Ca(n ,α )38Ar and 41K(p ,α )38Ar reactions have been identified as the key reactions governing the abundance of 41Ca, which is considered as a potential chronometer for solar system formation. So far, due to experimental limitations, the 41Ca(n ,α )38Ar reaction rate is solely based on statistical model calculations. In the present study, we have measured the time-inverse 38Ar(α ,n )41Ca and 38Ar(α ,p )41K reactions using an active target detector. The reactions were studied in inverse kinematics using a 133-MeV 38Ar beam and 4He as the active-gas target. Both excitation functions were measured simultaneously in the energy range of 6.8 ≤Ec .m .≤9.3 MeV. Using detailed balance the 41Ca(n ,α )38Ar and 41K(p ,α )38Ar reaction rates were determined, which suggested a 20% increase in the 41Ca yield from massive stars.

  8. Highly efficient targeted mutagenesis in one-cell mouse embryos mediated by the TALEN and CRISPR/Cas systems.

    PubMed

    Yasue, Akihiro; Mitsui, Silvia Naomi; Watanabe, Takahito; Sakuma, Tetsushi; Oyadomari, Seiichi; Yamamoto, Takashi; Noji, Sumihare; Mito, Taro; Tanaka, Eiji

    2014-07-16

    Since the establishment of embryonic stem (ES) cell lines, the combined use of gene targeting with homologous recombination has aided in elucidating the functions of various genes. However, the ES cell technique is inefficient and time-consuming. Recently, two new gene-targeting technologies have been developed: the transcription activator-like effector nuclease (TALEN) system, and the clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated protein (Cas) system. In addition to aiding researchers in solving conventional problems, these technologies can be used to induce site-specific mutations in various species for which ES cells have not been established. Here, by targeting the Fgf10 gene through RNA microinjection in one-cell mouse embryos with the TALEN and CRISPR/Cas systems, we produced the known limb-defect phenotypes of Fgf10-deficient embryos at the F0 generation. Compared to the TALEN system, the CRISPR/Cas system induced the limb-defect phenotypes with a strikingly higher efficiency. Our results demonstrate that although both gene-targeting technologies are useful, the CRISPR/Cas system more effectively elicits single-step biallelic mutations in mice.

  9. Infrared small target detection based on multiscale center-surround contrast measure

    NASA Astrophysics Data System (ADS)

    Fu, Hao; Long, Yunli; Zhu, Ran; An, Wei

    2018-04-01

    Infrared(IR) small target detection plays a critical role in the Infrared Search And Track (IRST) system. Although it has been studied for years, there are some difficulties remained to the clutter environment. According to the principle of human discrimination of small targets from a natural scene that there is a signature of discontinuity between the object and its neighboring regions, we develop an efficient method for infrared small target detection called multiscale centersurround contrast measure (MCSCM). First, to determine the maximum neighboring window size, an entropy-based window selection technique is used. Then, we construct a novel multiscale center-surround contrast measure to calculate the saliency map. Compared with the original image, the MCSCM map has less background clutters and noise residual. Subsequently, a simple threshold is used to segment the target. Experimental results show our method achieves better performance.

  10. The targeting of plant cellular systems by injected type III effector proteins.

    PubMed

    Lewis, Jennifer D; Guttman, David S; Desveaux, Darrell

    2009-12-01

    The battle between phytopathogenic bacteria and their plant hosts has revealed a diverse suite of strategies and mechanisms employed by the pathogen or the host to gain the higher ground. Pathogens continually evolve tactics to acquire host resources and dampen host defences. Hosts must evolve surveillance and defence systems that are sensitive enough to rapidly respond to a diverse range of pathogens, while reducing costly and damaging inappropriate misexpression. The primary virulence mechanism employed by many bacteria is the type III secretion system, which secretes and translocates effector proteins directly into the cells of their plant hosts. Effectors have diverse enzymatic functions and can target specific components of plant systems. While these effectors should favour bacterial fitness, the host may be able to thwart infection by recognizing the activity or presence of these foreign molecules and initiating retaliatory immune measures. We review the diverse host cellular systems exploited by bacterial effectors, with particular focus on plant proteins directly targeted by effectors. Effector-host interactions reveal different stages of the battle between pathogen and host, as well as the diverse molecular strategies employed by bacterial pathogens to hijack eukaryotic cellular systems.

  11. Experimental Impacts into Chondritic Targets. Part 1; Disruption of an L6 Chondrite by Multiple Impacts

    NASA Technical Reports Server (NTRS)

    Cintala, Mark J.; Horz, Friedrich

    2007-01-01

    A fragment of an L6 chondrite (ALH 85017,13) with an initial mass (M(sub 0)) of 464.1 g was the target in a series of experimental impacts in which the largest remaining fragment (M(sub R)) after each shot was impacted by a 3.18-mm ceramic sphere at a nominal speed of 2 km/s. This continued until the mass of the largest remaining piece was less than half the mass of the target presented to that shot (M(sub S)). Two chunks of Bushveldt gabbro with similar initial masses were also impacted under the same conditions until M(sub R) was less than half M(sub 0). The two gabbro targets required a total of 1.51x10(exp 7) and 1.75x10(exp 7) erg/g to attain 0.27 and 0.33 M(sub R)/M(sub 0), respectively; the chondrite, however, was considerably tougher, reaching 0.40 and 0.21 M(sub R)/M(sub 0) only after receiving 2.37x10(exp 7) and 3.10x10(exp 7) erg g-1, respectively. The combined ejecta and spallation products from the gabbro impacts were coarser than those from the chondrite and in sufficient quantities that the new surface areas exceeded those from the meteorite until the fifth shot in the chondrite series, which was the number of impacts required to disrupt each gabbro target (i.e., MR/M0 = 0.5). Unlike the behavior shown in previous regolith-evolution series, neither gabbro target produced an enhancement in the size fraction reflecting the mean size of the crystals composing the rock (about 3 mm), an effect possibly related to the width of the shock pulse. The original chondrite was so fine-grained and fractured, and the variance in its grain-size distribution so large, that effects related to grain-size were relegated to the <63- m fraction. Impacts into ALH 85017 produced abundant, fine-grained debris, but otherwise the slopes of its size distributions were comparable to those from other experiments involving natural and fabricated terrestrial targets. The characteristic slopes of the chondrite's size distributions, however, were notably more constant over the entire

  12. Experimental feedback linearisation of a vibrating system with a non-smooth nonlinearity

    NASA Astrophysics Data System (ADS)

    Lisitano, D.; Jiffri, S.; Bonisoli, E.; Mottershead, J. E.

    2018-03-01

    Input-output partial feedback linearisation is demonstrated experimentally for the first time on a system with non-smooth nonlinearity, a laboratory three degrees of freedom lumped mass system with a piecewise-linear spring. The output degree of freedom is located away from the nonlinearity so that the partial feedback linearisation possesses nonlinear internal dynamics. The dynamic behaviour of the linearised part is specified by eigenvalue assignment and an investigation of the zero dynamics is carried out to confirm stability of the overall system. A tuned numerical model is developed for use in the controller and to produce numerical outputs for comparison with experimental closed-loop results. A new limitation of the feedback linearisation method is discovered in the case of lumped mass systems - that the input and output must share the same degrees of freedom.

  13. An integrated CRISPR Bombyx mori genome editing system with improved efficiency and expanded target sites.

    PubMed

    Ma, Sanyuan; Liu, Yue; Liu, Yuanyuan; Chang, Jiasong; Zhang, Tong; Wang, Xiaogang; Shi, Run; Lu, Wei; Xia, Xiaojuan; Zhao, Ping; Xia, Qingyou

    2017-04-01

    Genome editing enabled unprecedented new opportunities for targeted genomic engineering of a wide variety of organisms ranging from microbes, plants, animals and even human embryos. The serial establishing and rapid applications of genome editing tools significantly accelerated Bombyx mori (B. mori) research during the past years. However, the only CRISPR system in B. mori was the commonly used SpCas9, which only recognize target sites containing NGG PAM sequence. In the present study, we first improve the efficiency of our previous established SpCas9 system by 3.5 folds. The improved high efficiency was also observed at several loci in both BmNs cells and B. mori embryos. Then to expand the target sites, we showed that two newly discovered CRISPR system, SaCas9 and AsCpf1, could also induce highly efficient site-specific genome editing in BmNs cells, and constructed an integrated CRISPR system. Genome-wide analysis of targetable sites was further conducted and showed that the integrated system cover 69,144,399 sites in B. mori genome, and one site could be found in every 6.5 bp. The efficiency and resolution of this CRISPR platform will probably accelerate both fundamental researches and applicable studies in B. mori, and perhaps other insects. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Hidden targets of ubiquitin proteasome system: To prevent diabetic nephropathy.

    PubMed

    Goru, Santosh Kumar; Kadakol, Almesh; Gaikwad, Anil Bhanudas

    2017-06-01

    Diabetic nephropathy (DN) is the major cause of end stage renal failure. Although, several therapeutic targets have emerged to prevent the progression of DN, the number of people with DN still continues to rise worldwide, suggesting an urgent need of novel targets to prevent DN completely. Currently, the role of ubiquitin proteasome system (UPS) has been highlighted in the pathogenesis and progression of various diseases like obesity, insulin resistance, atherosclerosis, cancers, neurodegerative disorders and including secondary complications of diabetes. UPS mainly involves in protein homeostatis through ubiquitination (post translational modification) and proteasomal degradation of various proteins. Ubiquitination, not only involves in proteasomal degradation, but also directs the substrate proteins to participate in multitude of cell signalling pathways. However, very little is known about ubiquitination and UPS in the progression of DN. This review mainly focuses on UPS and its components including E2 conjugating enzymes, E3 ligases and deubiquitinases (DUBs) in the development of DN and thus may help us to find novel therapeutic targets with in UPS to prevent DN completely in future. Copyright © 2017 Elsevier Ltd. All rights reserved.

  15. Experimental Air Pressure Tank Systems for Process Control Education

    ERIC Educational Resources Information Center

    Long, Christopher E.; Holland, Charles E.; Gatzke, Edward P.

    2006-01-01

    In process control education, particularly in the field of chemical engineering, there is an inherent need for industrially relevant hands-on apparatuses that enable one to bridge the gap between the theoretical content of coursework and real-world applications. At the University of South Carolina, two experimental air-pressure tank systems have…

  16. Risk assessment and experimental design in the development of a prolonged release drug delivery system with paliperidone.

    PubMed

    Iurian, Sonia; Turdean, Luana; Tomuta, Ioan

    2017-01-01

    This study focuses on the development of a drug product based on a risk assessment-based approach, within the quality by design paradigm. A prolonged release system was proposed for paliperidone (Pal) delivery, containing Kollidon ® SR as an insoluble matrix agent and hydroxypropyl cellulose, hydroxypropyl methylcellulose (HPMC), or sodium carboxymethyl cellulose as a hydrophilic polymer. The experimental part was preceded by the identification of potential sources of variability through Ishikawa diagrams, and failure mode and effects analysis was used to deliver the critical process parameters that were further optimized by design of experiments. A D-optimal design was used to investigate the effects of Kollidon SR ratio ( X 1 ), the type of hydrophilic polymer ( X 2 ), and the percentage of hydrophilic polymer ( X 3 ) on the percentages of dissolved Pal over 24 h ( Y 1 - Y 9 ). Effects expressed as regression coefficients and response surfaces were generated, along with a design space for the preparation of a target formulation in an experimental area with low error risk. The optimal formulation contained 27.62% Kollidon SR and 8.73% HPMC and achieved the prolonged release of Pal, with low burst effect, at ratios that were very close to the ones predicted by the model. Thus, the parameters with the highest impact on the final product quality were studied, and safe ranges were established for their variations. Finally, a risk mitigation and control strategy was proposed to assure the quality of the system, by constant process monitoring.

  17. Experimental System of Solar Adsorption Refrigeration with Concentrated Collector.

    PubMed

    Yuan, Z X; Li, Y X; Du, C X

    2017-10-18

    To improve the performance of solar adsorption refrigeration, an experimental system with a solar concentration collector was set up and investigated. The main components of the system were the adsorbent bed, the condenser, the evaporator, the cooling sub-system, and the solar collector. In the first step of the experiment, the vapor-saturated bed was heated by the solar radiation under closed conditions, which caused the bed temperature and pressure to increase. When the bed pressure became high enough, the bed was switched to connect to the condenser, thus water vapor flowed continually from the bed to the condenser to be liquefied. Next, the bed needed to cool down after the desorption. In the solar-shielded condition, achieved by aluminum foil, the circulating water loop was opened to the bed. With the water continually circulating in the bed, the stored heat in the bed was took out and the bed pressure decreased accordingly. When the bed pressure dropped below the saturation pressure at the evaporation temperature, the valve to the evaporator was opened. A mass of water vapor rushed into the bed and was adsorbed by the zeolite material. With the massive vaporization of the water in the evaporator, the refrigeration effect was generated finally. The experimental result has revealed that both the COP (coefficient of the performance of the system) and the SCP (specific cooling power of the system) of the SAPO-34 zeolite was greater than that of the ZSM-5 zeolite, no matter whether the adsorption time was longer or shorter. The system of the SAPO-34 zeolite generated a maximum COP of 0.169.

  18. GEANT4 simulation of cyclotron radioisotope production in a solid target.

    PubMed

    Poignant, F; Penfold, S; Asp, J; Takhar, P; Jackson, P

    2016-05-01

    The use of radioisotopes in nuclear medicine is essential for diagnosing and treating cancer. The optimization of their production is a key factor in maximizing the production yield and minimizing the associated costs. An efficient approach to this problem is the use of Monte Carlo simulations prior to experimentation. By predicting isotopes yields, one can study the isotope of interest expected activity for different energy ranges. One can also study the target contamination with other radioisotopes, especially undesired radioisotopes of the wanted chemical element which are difficult to separate from the irradiated target and might result in increasing the dose when delivering the radiopharmaceutical product to the patient. The aim of this work is to build and validate a Monte Carlo simulation platform using the GEANT4 toolkit to model the solid target system of the South Australian Health and Medical Research Institute (SAHMRI) GE Healthcare PETtrace cyclotron. It includes a GEANT4 Graphical User Interface (GUI) where the user can modify simulation parameters such as the energy, shape and current of the proton beam, the target geometry and material, the foil geometry and material and the time of irradiation. The paper describes the simulation and presents a comparison of simulated and experimental/theoretical yields for various nuclear reactions on an enriched nickel 64 target using the GEANT4 physics model QGSP_BIC_AllHP, a model recently developed to evaluate with high precision the interaction of protons with energies below 200MeV available in Geant4 version 10.1. The simulation yield of the (64)Ni(p,n)(64)Cu reaction was found to be 7.67±0.074 mCi·μA(-1) for a target energy range of 9-12MeV. Szelecsenyi et al. (1993) gives a theoretical yield of 6.71mCi·μA(-1) and an experimental yield of 6.38mCi·μA(-1). The (64)Ni(p,n)(64)Cu cross section obtained with the simulation was also verified against the yield predicted from the nuclear database TENDL and

  19. Progress on LMJ targets for ignition

    NASA Astrophysics Data System (ADS)

    Cherfils-Clérouin, C.; Boniface, C.; Bonnefille, M.; Fremerye, P.; Galmiche, D.; Gauthier, P.; Giorla, J.; Lambert, F.; Laffite, S.; Liberatore, S.; Loiseau, P.; Malinie, G.; Masse, L.; Masson-Laborde, P. E.; Monteil, M. C.; Poggi, F.; Seytor, P.; Wagon, F.; Willien, J. L.

    2010-08-01

    Targets designed to produce ignition on the Laser MegaJoule are presented. The LMJ experimental plans include the attempt of ignition and burn of an ICF capsule with 160 laser beams, delivering up to 1.4MJ and 380TW. New targets needing reduced laser energy with only a small decrease in robustness have then been designed for this purpose. Working specifically on the coupling efficiency parameter, i.e. the ratio of the energy absorbed by the capsule to the laser energy, has led to the design of a rugby-shaped cocktail hohlraum. 1D and 2D robustness evaluations of these different targets shed light on critical points for ignition, that can be traded off by tightening some specifications or by preliminary experimental and numerical tuning experiments.

  20. System integration of RF based negative ion experimental facility at IPR

    NASA Astrophysics Data System (ADS)

    Bansal, G.; Bandyopadhyay, M.; Singh, M. J.; Gahlaut, A.; Soni, J.; Pandya, K.; Parmar, K. G.; Sonara, J.; Chakraborty, A.

    2010-02-01

    The setting up of RF based negative ion experimental facility shall witness the beginning of experiments on the negative ion source fusion applications in India. A 1 MHz RF generator shall launch 100 kW RF power into a single driver on the plasma source to produce a plasma of density ~5 × 1012 cm-3. The source can deliver a negative ion beam of ~10 A with a current density of ~30 mA/cm2 and accelerated to 35 kV through an electrostatic ion accelerator. The experimental system is similar to a RF based negative ion source, BATMAN, presently operating at IPP. The subsystems for source operation are designed and procured principally from indigenous resources, keeping the IPP configuration as a base line. The operation of negative ion source is supported by many subsystems e.g. vacuum pumping system with gate valves, cooling water system, gas feed system, cesium delivery system, RF generator, high voltage power supplies, data acquisition and control system, and different diagnostics. The first experiments of negative ion source are expected to start at IPR from the middle of 2009.

  1. A multi-scale experimental and simulation approach for fractured subsurface systems

    NASA Astrophysics Data System (ADS)

    Viswanathan, H. S.; Carey, J. W.; Frash, L.; Karra, S.; Hyman, J.; Kang, Q.; Rougier, E.; Srinivasan, G.

    2017-12-01

    Fractured systems play an important role in numerous subsurface applications including hydraulic fracturing, carbon sequestration, geothermal energy and underground nuclear test detection. Fractures that range in scale from microns to meters and their structure control the behavior of these systems which provide over 85% of our energy and 50% of US drinking water. Determining the key mechanisms in subsurface fractured systems has been impeded due to the lack of sophisticated experimental methods to measure fracture aperture and connectivity, multiphase permeability, and chemical exchange capacities at the high temperature, pressure, and stresses present in the subsurface. In this study, we developed and use microfluidic and triaxial core flood experiments required to reveal the fundamental dynamics of fracture-fluid interactions. In addition we have developed high fidelity fracture propagation and discrete fracture network flow models to simulate these fractured systems. We also have developed reduced order models of these fracture simulators in order to conduct uncertainty quantification for these systems. We demonstrate an integrated experimental/modeling approach that allows for a comprehensive characterization of fractured systems and develop models that can be used to optimize the reservoir operating conditions over a range of subsurface conditions.

  2. Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models.

    PubMed

    Jacobo-Estrada, Tania; Santoyo-Sánchez, Mitzi; Thévenod, Frank; Barbier, Olivier

    2017-07-22

    Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney).

  3. Cadmium Handling, Toxicity and Molecular Targets Involved during Pregnancy: Lessons from Experimental Models

    PubMed Central

    Santoyo-Sánchez, Mitzi; Thévenod, Frank; Barbier, Olivier

    2017-01-01

    Even decades after the discovery of Cadmium (Cd) toxicity, research on this heavy metal is still a hot topic in scientific literature: as we wrote this review, more than 1440 scientific articles had been published and listed by the PubMed.gov website during 2017. Cadmium is one of the most common and harmful heavy metals present in our environment. Since pregnancy is a very particular physiological condition that could impact and modify essential pathways involved in the handling of Cd, the prenatal life is a critical stage for exposure to this non-essential element. To give the reader an overview of the possible mechanisms involved in the multiple organ toxic effects in fetuses after the exposure to Cd during pregnancy, we decided to compile some of the most relevant experimental studies performed in experimental models and to summarize the advances in this field such as the Cd distribution and the factors that could alter it (diet, binding-proteins and membrane transporters), the Cd-induced toxicity in dams (preeclampsia, fertility, kidney injury, alteration in essential element homeostasis and bone mineralization), in placenta and in fetus (teratogenicity, central nervous system, liver and kidney). PMID:28737682

  4. An experimental model to investigate the targeting accuracy of MR-guided focused ultrasound ablation in liver.

    PubMed

    Petrusca, Lorena; Viallon, Magalie; Breguet, Romain; Terraz, Sylvain; Manasseh, Gibran; Auboiroux, Vincent; Goget, Thomas; Baboi, Loredana; Gross, Patrick; Sekins, K Michael; Becker, Christoph D; Salomir, Rares

    2014-01-16

    Magnetic Resonance-guided High Intensity Focused Ultrasound (MRgHIFU) is a hybrid technology that aims to offer non-invasive thermal ablation of targeted tumors or other pathological tissues. Acoustic aberrations and non-linear wave propagating effects may shift the focal point significantly away from the prescribed (or, theoretical) position. It is therefore mandatory to evaluate the spatial accuracy of ablation for a given HIFU protocol and/or device. We describe here a method for producing a user-defined ballistic target as an absolute reference marker for MRgHIFU ablations. The investigated method is based on trapping a mixture of MR contrast agent and histology stain using radiofrequency (RF) ablation causing cell death and coagulation. A dedicated RF-electrode was used for the marker fixation as follows: a RF coagulation (4 W, 15 seconds) and injection of the mixture followed by a second RF coagulation. As a result, the contrast agent/stain is encapsulated in the intercellular space. Ultrasonography imaging was performed during the procedure, while high resolution T1w 3D VIBE MR acquisition was used right after to identify the position of the ballistic marker and hence the target tissue. For some cases, after the marker fixation procedure, HIFU volumetric ablations were produced by a phased-array HIFU platform. First ex vivo experiments were followed by in vivo investigation on four rabbits in thigh muscle and six pigs in liver, with follow-up at Day 7. At the end of the procedure, no ultrasound indication of the marker's presence could be observed, while it was clearly visible under MR and could be conveniently used to prescribe the HIFU ablation, centered on the so-created target. The marker was identified at Day 7 after treatment, immediately after animal sacrifice, after 3 weeks of post-mortem formalin fixation and during histology analysis. Its size ranged between 2.5 and 4 mm. Experimental validation of this new ballistic marker method was performed for

  5. STEP--a System for Teaching Experimental Psychology using E-Prime.

    PubMed

    MacWhinney, B; St James, J; Schunn, C; Li, P; Schneider, W

    2001-05-01

    Students in psychology need to learn to design and analyze their own experiments. However, software that allows students to build experiments on their own has been limited in a variety of ways. The shipping of the first full release of the E-Prime system later this year will open up a new opportunity for addressing this problem. Because E-Prime promises to become the standard for building experiments in psychology, it is now possible to construct a Web-based resource that uses E-Prime as the delivery engine for a wide variety of instructional materials. This new system, funded by the National Science Foundation, is called STEP (System for the Teaching of Experimental Psychology). The goal of the STEP Project is to provide instructional materials that will facilitate the use of E-Prime in various learning contexts. We are now compiling a large set of classic experiments implemented in E-Prime and available over the Internet from http://step.psy.cmu.edu. The Web site also distributes instructional materials for building courses in experimental psychology based on E-Prime.

  6. Pulsar-aided SETI experimental observations

    NASA Technical Reports Server (NTRS)

    Heidmann, J.; Biraud, F.; Tarter, J.

    1989-01-01

    The rotational frequencies of pulsars are used to select preferred radio frequencies for SETI. Pulsar rotational frequencies are converted into SETI frequencies in the 1-10 GHz Galactic radio window. Experimental observations using the frequencies are conducted for target stars closer than 25 parsecs, unknown targets in a globular cluster, and unknown targets in the Galaxy closer than 2.5 kpc. The status of these observations is discussed.

  7. Laser long-range remote-sensing program experimental results

    NASA Astrophysics Data System (ADS)

    Highland, Ronald G.; Shilko, Michael L.; Fox, Marsha J.; Gonglewski, John D.; Czyzak, Stanley R.; Dowling, James A.; Kelly, Brian; Pierrottet, Diego F.; Ruffatto, Donald; Loando, Sharon; Matsuura, Chris; Senft, Daniel C.; Finkner, Lyle; Rae, Joe; Gallegos, Joe

    1995-12-01

    A laser long range remote sensing (LRS) program is being conducted by the United States Air Force Phillips Laboratory (AF/PL). As part of this program, AF/PL is testing the feasibility of developing a long path CO(subscript 2) laser-based DIAL system for remote sensing. In support of this program, the AF/PL has recently completed an experimental series using a 21 km slant- range path (3.05 km ASL transceiver height to 0.067 km ASL target height) at its Phillips Laboratory Air Force Maui Optical Station (AMOS) facility located on Maui, Hawaii. The dial system uses a 3-joule, (superscript 13)C isotope laser coupled into a 0.6 m diameter telescope. The atmospheric optical characterization incorporates information from an infrared scintillometer co-aligned to the laser path, atmospheric profiles from weather balloons launched from the target site, and meteorological data from ground stations at AMOS and the target site. In this paper, we report a description of the experiment configuration, a summary of the results, a summary of the atmospheric conditions and their implications to the LRS program. The capability of such a system for long-range, low-angle, slant-path remote sensing is discussed. System performance issues relating to both coherent and incoherent detection methods, atmospheric limitations, as well as, the development of advanced models to predict performance of long range scenarios are presented.

  8. Can healthy, young adults uncover personal details of unknown target individuals in their dreams?

    PubMed

    Smith, Carlyle

    2013-01-01

    We investigated the possibility that undergraduate college students could incubate dreams containing information about unknown target individuals with significant life problems. In Experiment 1, students provided two baseline dreams. They were then exposed to a photo of an individual and invited to dream about a health problem (unknown to them and the experimenter) of that individual and asked to provide two more dreams. From a class of 65 students, 12 dreamers volunteered dreams about the unknown target. In Experiment 2, 66 students were asked to dream about the life problems of a second individual, simply by looking at the photo (experimental group). Another 56 students were exposed to this same paradigm, but the photo that they examined was computer generated and the target individual was fictitious (control group). The dream elements were objectively scored with categories devised using the Hall-Van de Castle system as a model. Data were ordinal, and the nonparametric Wilcoxon signed rank test was used to examine preincubation (baseline) versus postincubation (photo examination and incubation) dream content in Experiment 1. In Experiment 2, a Z score for proportions was used to compare differences in frequency of devised categories between experimental and control groups. In Experiment 1, the comparison of postincubation dreams (all categories combined) was significant compared with the preincubation dreams (Z = 2.09, P = .036). The postincubation dreams reflected the health problem of the target. In Experiment 2, the proportion of scored categories in experimental and control groups were compared at the preincubation and postincubation conditions. The proportions of "Combined" (all categories) was very significantly larger at the postincubation condition (Z = 6.27, P < .00001). The groups did not differ at the preincubation condition (Z = -1.12, not significant). Individual postincubation condition comparisons of the experimental versus control groups revealed

  9. TargetLink, a new method for identifying the endogenous target set of a specific microRNA in intact living cells.

    PubMed

    Xu, Yan; Chen, Yan; Li, Daliang; Liu, Qing; Xuan, Zhenyu; Li, Wen-Hong

    2017-02-01

    MicroRNAs are small non-coding RNAs acting as posttranscriptional repressors of gene expression. Identifying mRNA targets of a given miRNA remains an outstanding challenge in the field. We have developed a new experimental approach, TargetLink, that applied locked nucleic acid (LNA) as the affinity probe to enrich target genes of a specific microRNA in intact cells. TargetLink also consists a rigorous and systematic data analysis pipeline to identify target genes by comparing LNA-enriched sequences between experimental and control samples. Using miR-21 as a test microRNA, we identified 12 target genes of miR-21 in a human colorectal cancer cell by this approach. The majority of the identified targets interacted with miR-21 via imperfect seed pairing. Target validation confirmed that miR-21 repressed the expression of the identified targets. The cellular abundance of the identified miR-21 target transcripts varied over a wide range, with some targets expressed at a rather low level, confirming that both abundant and rare transcripts are susceptible to regulation by microRNAs, and that TargetLink is an efficient approach for identifying the target set of a specific microRNA in intact cells. C20orf111, one of the novel targets identified by TargetLink, was found to reside in the nuclear speckle and to be reliably repressed by miR-21 through the interaction at its coding sequence.

  10. Modeling and validation of photometric characteristics of space targets oriented to space-based observation.

    PubMed

    Wang, Hongyuan; Zhang, Wei; Dong, Aotuo

    2012-11-10

    A modeling and validation method of photometric characteristics of the space target was presented in order to track and identify different satellites effectively. The background radiation characteristics models of the target were built based on blackbody radiation theory. The geometry characteristics of the target were illustrated by the surface equations based on its body coordinate system. The material characteristics of the target surface were described by a bidirectional reflectance distribution function model, which considers the character of surface Gauss statistics and microscale self-shadow and is obtained by measurement and modeling in advance. The contributing surfaces of the target to observation system were determined by coordinate transformation according to the relative position of the space-based target, the background radiation sources, and the observation platform. Then a mathematical model on photometric characteristics of the space target was built by summing reflection components of all the surfaces. Photometric characteristics simulation of the space-based target was achieved according to its given geometrical dimensions, physical parameters, and orbital parameters. Experimental validation was made based on the scale model of the satellite. The calculated results fit well with the measured results, which indicates the modeling method of photometric characteristics of the space target is correct.

  11. Targeting endogenous proteins for degradation through the affinity-directed protein missile system.

    PubMed

    Fulcher, Luke J; Hutchinson, Luke D; Macartney, Thomas J; Turnbull, Craig; Sapkota, Gopal P

    2017-05-01

    Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel-Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins. © 2017 The Authors.

  12. Targeting endogenous proteins for degradation through the affinity-directed protein missile system

    PubMed Central

    Fulcher, Luke J.; Hutchinson, Luke D.; Macartney, Thomas J.; Turnbull, Craig

    2017-01-01

    Targeted proteolysis of endogenous proteins is desirable as a research toolkit and in therapeutics. CRISPR/Cas9-mediated gene knockouts are irreversible and often not feasible for many genes. Similarly, RNA interference approaches necessitate prolonged treatments, can lead to incomplete knockdowns and are often associated with off-target effects. Targeted proteolysis can overcome these limitations. In this report, we describe an affinity-directed protein missile (AdPROM) system that harbours the von Hippel–Lindau (VHL) protein, the substrate receptor of the Cullin2 (CUL2) E3 ligase complex, tethered to polypeptide binders that selectively bind and recruit endogenous target proteins to the CUL2-E3 ligase complex for ubiquitination and proteasomal degradation. By using synthetic monobodies that selectively bind the protein tyrosine phosphatase SHP2 and a camelid-derived VHH nanobody that selectively binds the human ASC protein, we demonstrate highly efficient AdPROM-mediated degradation of endogenous SHP2 and ASC in human cell lines. We show that AdPROM-mediated loss of SHP2 in cells impacts SHP2 biology. This study demonstrates for the first time that small polypeptide binders that selectively recognize endogenous target proteins can be exploited for AdPROM-mediated destruction of the target proteins. PMID:28490657

  13. Atmosphere stabilization and element recycle in an experimental mouse-algal system

    NASA Technical Reports Server (NTRS)

    Smernoff, David T.

    1986-01-01

    Life support systems based on bioregeneration rely on the control and manipulation of organisms. Experiments conducted with a gas-closed mouse-algal system designed to investigate principles of photosynthetic gas exchange focus primarily on observing gas exchange phenomena under varying algal environmental conditions and secondarily on studying element cycling through compartments of the experimental system. Inherent instabilities exit between the uptake and release of carbon dioxide CO2 and oxygen O2 by the mouse and algae. Variations in light intensity and cell density alter the photosynthetic rate of the algae and enable maintenance of physiologic concentrations of CO2 and O2. Different nitrogen sources (urea and nitrate) result in different algal assimilatory quotients (AQ). Combinations of photosynthetic rate and AQ ratio manipulations have been examined for their potential in stabilizing atmospheric gas concentrations in the gas-closed algal-mouse system. Elemental mass balances through the experimental systems compartments are being studied with the concurrent development of a mathematical simulation model. Element cycling experiments include quantification of elemental flows through system compartments and wet oxidation of system waste materials for use as an algal nutrient source. Oxidized waste products demonstrate inhibitory properties although dilution has been shown to allow normal growth.

  14. Parametric model of servo-hydraulic actuator coupled with a nonlinear system: Experimental validation

    NASA Astrophysics Data System (ADS)

    Maghareh, Amin; Silva, Christian E.; Dyke, Shirley J.

    2018-05-01

    Hydraulic actuators play a key role in experimental structural dynamics. In a previous study, a physics-based model for a servo-hydraulic actuator coupled with a nonlinear physical system was developed. Later, this dynamical model was transformed into controllable canonical form for position tracking control purposes. For this study, a nonlinear device is designed and fabricated to exhibit various nonlinear force-displacement profiles depending on the initial condition and the type of materials used as replaceable coupons. Using this nonlinear system, the controllable canonical dynamical model is experimentally validated for a servo-hydraulic actuator coupled with a nonlinear physical system.

  15. Inclusion of quasi-experimental studies in systematic reviews of health systems research.

    PubMed

    Rockers, Peter C; Røttingen, John-Arne; Shemilt, Ian; Tugwell, Peter; Bärnighausen, Till

    2015-04-01

    Systematic reviews of health systems research commonly limit studies for evidence synthesis to randomized controlled trials. However, well-conducted quasi-experimental studies can provide strong evidence for causal inference. With this article, we aim to stimulate and inform discussions on including quasi-experiments in systematic reviews of health systems research. We define quasi-experimental studies as those that estimate causal effect sizes using exogenous variation in the exposure of interest that is not directly controlled by the researcher. We incorporate this definition into a non-hierarchical three-class taxonomy of study designs - experiments, quasi-experiments, and non-experiments. Based on a review of practice in three disciplines related to health systems research (epidemiology, economics, and political science), we discuss five commonly used study designs that fit our definition of quasi-experiments: natural experiments, instrumental variable analyses, regression discontinuity analyses, interrupted times series studies, and difference studies including controlled before-and-after designs, difference-in-difference designs and fixed effects analyses of panel data. We further review current practices regarding quasi-experimental studies in three non-health fields that utilize systematic reviews (education, development, and environment studies) to inform the design of approaches for synthesizing quasi-experimental evidence in health systems research. Ultimately, the aim of any review is practical: to provide useful information for policymakers, practitioners, and researchers. Future work should focus on building a consensus among users and producers of systematic reviews regarding the inclusion of quasi-experiments. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  16. A Production System Model of Capturing Reactive Moving Targets. M.S. Thesis

    NASA Technical Reports Server (NTRS)

    Jagacinski, R. J.; Plamondon, B. D.; Miller, R. A.

    1984-01-01

    Subjects manipulated a control stick to position a cursor over a moving target that reacted with a computer-generated escape strategy. The cursor movements were described at two levels of abstraction. At the upper level, a production system described transitions among four modes of activity; rapid acquisition, close following, a predictive mode, and herding. Within each mode, differential equations described trajectory-generating mechanisms. A simulation of this two-level model captures the targets in a manner resembling the episodic time histories of human subjects.

  17. The p38α mitogen-activated protein kinase as a central nervous system drug discovery target

    PubMed Central

    Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

    2008-01-01

    Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38α mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38α MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38α MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38α MAPK in neurodegenerative disorders. PMID:19090985

  18. The p38alpha mitogen-activated protein kinase as a central nervous system drug discovery target.

    PubMed

    Borders, Aaron S; de Almeida, Lucia; Van Eldik, Linda J; Watterson, D Martin

    2008-12-03

    Protein kinases are critical modulators of a variety of cellular signal transduction pathways, and abnormal phosphorylation events can be a cause or contributor to disease progression in a variety of disorders. This has led to the emergence of protein kinases as an important new class of drug targets for small molecule therapeutics. A serine/threonine protein kinase, p38alpha mitogen-activated protein kinase (MAPK), is an established therapeutic target for peripheral inflammatory disorders because of its critical role in regulation of proinflammatory cytokine production. There is increasing evidence that p38alpha MAPK is also an important regulator of proinflammatory cytokine levels in the central nervous system, raising the possibility that the kinase may be a drug discovery target for central nervous system disorders where cytokine overproduction contributes to disease progression. Development of bioavailable, central nervous system-penetrant p38alpha MAPK inhibitors provides the required foundation for drug discovery campaigns targeting p38alpha MAPK in neurodegenerative disorders.

  19. Theranostic nanoparticles carrying doxorubicin attenuate targeting ligand specific antibody responses following systemic delivery.

    PubMed

    Yang, Emmy; Qian, Weiping; Cao, Zehong; Wang, Liya; Bozeman, Erica N; Ward, Christina; Yang, Bin; Selvaraj, Periasamy; Lipowska, Malgorzata; Wang, Y Andrew; Mao, Hui; Yang, Lily

    2015-01-01

    Understanding the effects of immune responses on targeted delivery of nanoparticles is important for clinical translations of new cancer imaging and therapeutic nanoparticles. In this study, we found that repeated administrations of magnetic iron oxide nanoparticles (IONPs) conjugated with mouse or human derived targeting ligands induced high levels of ligand specific antibody responses in normal and tumor bearing mice while injections of unconjugated mouse ligands were weakly immunogenic and induced a very low level of antibody response in mice. Mice that received intravenous injections of targeted and polyethylene glycol (PEG)-coated IONPs further increased the ligand specific antibody production due to differential uptake of PEG-coated nanoparticles by macrophages and dendritic cells. However, the production of ligand specific antibodies was markedly inhibited following systemic delivery of theranostic nanoparticles carrying a chemotherapy drug, doxorubicin. Targeted imaging and histological analysis revealed that lack of the ligand specific antibodies led to an increase in intratumoral delivery of targeted nanoparticles. Results of this study support the potential of further development of targeted theranostic nanoparticles for the treatment of human cancers.

  20. Target-in-the-loop high-power adaptive phase-locked fiber laser array using single-frequency dithering technique

    NASA Astrophysics Data System (ADS)

    Tao, R.; Ma, Y.; Si, L.; Dong, X.; Zhou, P.; Liu, Z.

    2011-11-01

    We present a theoretical and experimental study of a target-in-the-loop (TIL) high-power adaptive phase-locked fiber laser array. The system configuration of the TIL adaptive phase-locked fiber laser array is introduced, and the fundamental theory for TIL based on the single-dithering technique is deduced for the first time. Two 10-W-level high-power fiber amplifiers are set up and adaptive phase locking of the two fiber amplifiers is accomplished successfully by implementing a single-dithering algorithm on a signal processor. The experimental results demonstrate that the optical phase noise for each beam channel can be effectively compensated by the TIL adaptive optics system under high-power applications and the fringe contrast on a remotely located extended target is advanced from 12% to 74% for the two 10-W-level fiber amplifiers.

  1. Production and characterization of pure cryogenic inertial fusion targets

    NASA Astrophysics Data System (ADS)

    Boyd, B. A.; Kamerman, G. W.

    An experimental cryogenic inertial fusion target generator and two optical techniques for automated target inspection are described. The generator produces 100 microns diameter solid hydrogen spheres at a rate compatible with fueling requirements of conceptual inertial fusion power plants. A jet of liquified hydrogen is disrupted into droplets by an ultrasonically excited nozzle. The droplets solidify into microspheres while falling through a chamber maintained below the hydrogen triple point pressure. Stable operation of the generator has been demonstrated for up to three hours. The optical inspection techniques are computer aided photomicrography and coarse diffraction pattern analysis (CDPA). The photomicrography system uses a conventional microscope coupled to a computer by a solid state camera and digital image memory. The computer enhances the stored image and performs feature extraction to determine pellet parameters. The CDPA technique uses Fourier transform optics and a special detector array to perform optical processing of a target image.

  2. Why Targeted Therapies are Necessary for Systemic Lupus Erythematosus

    PubMed Central

    Durcan, Laura; Petri, Michelle

    2016-01-01

    Systemic lupus erythematosus (SLE) continues to have important morbidity and accelerated mortality despite therapeutic advances. Targeted therapies offer the possibility of improved efficacy with fewer side-effects. Current management strategies rely heavily on non-specific immunosuppressive agents. Prednisone, in particular, is responsible for a considerable burden of later organ damage. There are a multitude of diverse mechanisms of disease activity, immunogenic abnormalities and clinical manifestations to take into consideration in SLE. Many targeted agents with robust mechanistic pre-clinical data and promising early phase studies have ultimately been disappointing in phase III randomized controlled studies. Recent efforts have focused on B cell therapies, in particular given the success of belimumab in clinical trials, with limited success. We remain optimistic regarding other specific therapies being evaluated including interferon alpha blockade. It is likely that in SLE, given the heterogeneity of the population involved, precision medicine is needed, rather than expecting that any single biologic will be universally effective. PMID:27497251

  3. Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia.

    PubMed

    Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

    2016-02-03

    Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%-87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy--introducing Cas9 and sgRNA expression cassettes sequentially into petunia--can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation.

  4. Clustered carbohydrates as a target for natural killer cells: a model system.

    PubMed

    Kovalenko, Elena I; Abakushina, Elena; Telford, William; Kapoor, Veena; Korchagina, Elena; Khaidukov, Sergei; Molotkovskaya, Irina; Sapozhnikov, Alexander; Vlaskin, Pavel; Bovin, Nicolai

    2007-03-01

    Membrane-associated oligosaccharides are known to take part in interactions between natural killer (NK) cells and their targets and modulate NK cell activity. A model system was therefore developed using synthetic glycoconjugates as tools to modify the carbohydrate pattern on NK target cell surfaces. NK cells were then assessed for function in response to synthetic glycoconjugates, using both cytolysis-associated caspase 6 activation measured by flow cytometry and IFN-gamma production. Lipophilic neoglycoconjugates were synthesized to provide their easy incorporation into the target cell membranes and to make carbohydrate residues available for cell-cell interactions. While incorporation was successful based on fluorescence monitoring, glycoconjugate incorporation did not evoke artifactual changes in surface antigen expression, and had no negative effect on cell viability. Glycoconjugates contained Le(x), sulfated Le(x), and Le(y) sharing the common structure motif trisaccharide Le(x) were revealed to enhance cytotoxicity mediated specifically by CD16 +CD56+NK cells. The glycoconjugate effects were dependent on saccharide presentation in a polymeric form. Only polymeric, or clustered, but not monomeric glycoconjugates resulted in alteration of cytotoxicity in our system, suggesting that appropriate presentation is critical for carbohydrate recognition and subsequent biological effects.

  5. Exploiting the CRISPR/Cas9 System for Targeted Genome Mutagenesis in Petunia

    PubMed Central

    Zhang, Bin; Yang, Xia; Yang, Chunping; Li, Mingyang; Guo, Yulong

    2016-01-01

    Recently, CRISPR/Cas9 technology has emerged as a powerful approach for targeted genome modification in eukaryotic organisms from yeast to human cell lines. Its successful application in several plant species promises enormous potential for basic and applied plant research. However, extensive studies are still needed to assess this system in other important plant species, to broaden its fields of application and to improve methods. Here we showed that the CRISPR/Cas9 system is efficient in petunia (Petunia hybrid), an important ornamental plant and a model for comparative research. When PDS was used as target gene, transgenic shoot lines with albino phenotype accounted for 55.6%–87.5% of the total regenerated T0 Basta-resistant lines. A homozygous deletion close to 1 kb in length can be readily generated and identified in the first generation. A sequential transformation strategy—introducing Cas9 and sgRNA expression cassettes sequentially into petunia—can be used to make targeted mutations with short indels or chromosomal fragment deletions. Our results present a new plant species amenable to CRIPR/Cas9 technology and provide an alternative procedure for its exploitation. PMID:26837606

  6. Molecular Mechanisms of RNA-Targeting by Cas13-containing Type VI CRISPR-Cas Systems.

    PubMed

    O'Connell, Mitchell

    2018-06-22

    Prokaryotic adaptive immune systems use CRISPRs (Clustered Regularly Interspaced Short Palindromic Repeats) and CRISPR associated (Cas) proteins for RNA-guided cleavage of foreign genetic elements. The focus of this review, Type VI CRISPR-Cas systems, include a single protein known as Cas13 (formerly C2c2), that when assembled with a crRNA forms a crRNA-guided RNA-targeting effector complex. Type VI CRISPR-Cas systems can be divided into four subtypes (A-D) based on Cas13 phylogeny. All Cas13 proteins studied to date possess two enzymatically distinct ribonuclease activities that are required for optimal interference. One RNase is responsible for pre-crRNA processing to form mature Type VI interference complexes, while the other RNase activity provided by the two HEPN (Higher Eukaryotes and Prokaryotes Nucleotide-binding) domains, is required for degradation of target RNA during viral interference. In this review, I will compare and contrast what is known about the molecular architecture and behavior of Type VI (A-D) CRISPR-Cas13 interference complexes, how this allows them to carry out their RNA-targeting function, how Type VI accessory proteins are able to modulate Cas13 activity, and how together all of these features have led to the rapid development of a range of RNA-targeting applications. Throughout I will also discuss some of the outstanding questions regarding Cas13's molecular behavior, and its role in bacterial adaptive immunity and RNA-targeting applications. Copyright © 2018. Published by Elsevier Ltd.

  7. Measurement of the target current by inductive probe during laser interaction on terawatt laser system PALS.

    PubMed

    Cikhardt, J; Krása, J; De Marco, M; Pfeifer, M; Velyhan, A; Krouský, E; Cikhardtová, B; Klír, D; Rezáč, K; Ullschmied, J; Skála, J; Kubeš, P; Kravárik, J

    2014-10-01

    Measurements of the return-current flowing through a solid target irradiated with the sub-nanosecond kJ-class Prague Asterix Laser System is reported. A new inductive target probe was developed which allows us measuring the target current derivative in a kA/ns range. The dependences of the target current on the laser pulse energy for cooper, graphite, and polyethylene targets are reported. The experiment shows that the target current is proportional to the deposited laser energy and is strongly affected by the shot-to-shot fluctuations. The corresponding maximum target charge exceeded a value of 10 μC. A return-current dependence of the electromagnetic pulse produced by the laser-target interaction is presented.

  8. Experimental millimeter-wave personal satellite communications system

    NASA Technical Reports Server (NTRS)

    Suzuki, Yoshiaki; Kimura, Shigeru; Shimada, Masaaki; Tanaka, Masato; Takahashi, Yasuhiro

    1991-01-01

    Communications Research Laboratory (CRL) has investigated an advanced millimeter (mm)-wave satellite communications system for personal use. Experiments in mm-wave personal satellite communication are to be conducted for 3 years using Japan's Engineering Test Satellite VI (ETS-VI). This paper describes an experimental mm-wave (43/38 GHz) personal satellite communication system, including an onboard transponder and an earth terminal. The on-board transponder is almost completed, and the ground experiment system is still in the design stage. The transponder employs advanced mm-wave solid state technology. It uses 38 GHz high power solid state amplifiers to accelerate the development of mm-wave solid state devices which are indispensable to personal earth terminals. The transponder consists of a 43 GHz receiver with a built-in low noise amplifier, an IF filter section with very narrow bandwidth to improve the carrier-to-noise power ratio of the weak personal communication signal, and two high power amplifiers using newly developed high power Gallium Arsenide (GaAs) metal-semiconductor field effect transistors (MESFETs).

  9. A system for the measurement of gene targeting efficiency in human cell lines using an antibiotic resistance-GFP fusion gene.

    PubMed

    Konishi, Yuko; Karnan, Sivasundaram; Takahashi, Miyuki; Ota, Akinobu; Damdindorj, Lkhagvasuren; Hosokawa, Yoshitaka; Konishi, Hiroyuki

    2012-09-01

    Gene targeting in a broad range of human somatic cell lines has been hampered by inefficient homologous recombination. To improve this technology and facilitate its widespread application, it is critical to first have a robust and efficient research system for measuring gene targeting efficiency. Here, using a fusion gene consisting of hygromycin B phosphotransferase and 3'-truncated enhanced GFP (HygR-5' EGFP) as a reporter gene, we created a molecular system monitoring the ratio of homologous to random integration (H/R ratio) of targeting vectors into the genome. Cell clones transduced with a reporter vector containing HygR-5' EGFP were efficiently established from two human somatic cell lines. Established HygR-5' EGFP reporter clones retained their capacity to monitor gene targeting efficiency for a longer duration than a conventional reporter system using an unfused 5' EGFP gene. With the HygR-5' EGFP reporter system, we reproduced previous findings of gene targeting frequency being up-regulated by the use of an adeno-associated viral (AAV) backbone, a promoter-trap system, or a longer homology arm in a targeting vector, suggesting that this system accurately monitors H/R ratio. Thus, our HygR-5' EGFP reporter system will assist in the development of an efficient AAV-based gene targeting technology.

  10. Feasibility Test of a Pulse Modulated Pressurization System for a High Altitude Supersonic Target Vehicle Propulsion System.

    DTIC Science & Technology

    1976-11-01

    pressure switch . The system was tested for stability of operation and accuracy of pressure control, using a High Altitude Supersonic Target (HAST...stable and accurate to approximately the deadband of the pressure switch used, 2 psi. (Author)

  11. Design and engineering of a target for x-ray Thomson scattering measurements on matter at extreme densities and gigabar pressures

    DOE PAGES

    Boehm, K. -J.; Hash, N.; Barker, D.; ...

    2016-06-24

    Reconciling the experimental and system requirements during the development of a new target system is one of the most challenging tasks in the design and engineering of targets used in the National Ignition Facility. Targets for the GigaBar 3 campaign were meant to allow the detection of extremely weak Thomson scattering from matter at extreme densities in the face of very bright backlighter and laser entry hole plasma emissions. The problem was to shield the detector sufficiently while maintaining beamline and view clearances, and observing target mass restrictions. A new construction process, based on a rapid prototype frame structure, wasmore » used to develop this target. As a result, details of the design process for these targets are described, and lessons from this development for production and target assembly teams are discussed.« less

  12. Blueprint for antimicrobial hit discovery targeting metabolic networks

    PubMed Central

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

    2010-01-01

    Advances in genome analysis, network biology, and computational chemistry have the potential to revolutionize drug discovery by combining system-level identification of drug targets with the atomistic modeling of small molecules capable of modulating their activity. To demonstrate the effectiveness of such a discovery pipeline, we deduced common antibiotic targets in Escherichia coli and Staphylococcus aureus by identifying shared tissue-specific or uniformly essential metabolic reactions in their metabolic networks. We then predicted through virtual screening dozens of potential inhibitors for several enzymes of these reactions and showed experimentally that a subset of these inhibited both enzyme activities in vitro and bacterial cell viability. This blueprint is applicable for any sequenced organism with high-quality metabolic reconstruction and suggests a general strategy for strain-specific antiinfective therapy. PMID:20080587

  13. CSI Flight Computer System and experimental test results

    NASA Technical Reports Server (NTRS)

    Sparks, Dean W., Jr.; Peri, F., Jr.; Schuler, P.

    1993-01-01

    This paper describes the CSI Computer System (CCS) and the experimental tests performed to validate its functionality. This system is comprised of two major components: the space flight qualified Excitation and Damping Subsystem (EDS) which performs controls calculations; and the Remote Interface Unit (RIU) which is used for data acquisition, transmission, and filtering. The flight-like RIU is the interface between the EDS and the sensors and actuators positioned on the particular structure under control. The EDS and RIU communicate over the MIL-STD-1553B, a space flight qualified bus. To test the CCS under realistic conditions, it was connected to the Phase-0 CSI Evolutionary Model (CEM) at NASA Langley Research Center. The following schematic shows how the CCS is connected to the CEM. Various tests were performed which validated the ability of the system to perform control/structures experiments.

  14. Validated MicroRNA Target Databases: An Evaluation.

    PubMed

    Lee, Yun Ji Diana; Kim, Veronica; Muth, Dillon C; Witwer, Kenneth W

    2015-11-01

    Preclinical Research Positive findings from preclinical and clinical studies involving depletion or supplementation of microRNA (miRNA) engender optimism about miRNA-based therapeutics. However, off-target effects must be considered. Predicting these effects is complicated. Each miRNA may target many gene transcripts, and the rules governing imperfectly complementary miRNA: target interactions are incompletely understood. Several databases provide lists of the relatively small number of experimentally confirmed miRNA: target pairs. Although incomplete, this information might allow assessment of at least some of the off-target effects. We evaluated the performance of four databases of experimentally validated miRNA: target interactions (miRWalk 2.0, miRTarBase, miRecords, and TarBase 7.0) using a list of 50 alphabetically consecutive genes. We examined the provided citations to determine the degree to which each interaction was experimentally supported. To assess stability, we tested at the beginning and end of a five-month period. Results varied widely by database. Two of the databases changed significantly over the course of 5 months. Most reported evidence for miRNA: target interactions were indirect or otherwise weak, and relatively few interactions were supported by more than one publication. Some returned results appear to arise from simplistic text searches that offer no insight into the relationship of the search terms, may not even include the reported gene or miRNA, and may thus, be invalid. We conclude that validation databases provide important information, but not all information in all extant databases is up-to-date or accurate. Nevertheless, the more comprehensive validation databases may provide useful starting points for investigation of off-target effects of proposed small RNA therapies. © 2015 Wiley Periodicals, Inc.

  15. Implementation of an experimental fault-tolerant memory system

    NASA Technical Reports Server (NTRS)

    Carter, W. C.; Mccarthy, C. E.

    1976-01-01

    The experimental fault-tolerant memory system described in this paper has been designed to enable the modular addition of spares, to validate the theoretical fault-secure and self-testing properties of the translator/corrector, to provide a basis for experiments using the new testing and correction processes for recovery, and to determine the practicality of such systems. The hardware design and implementation are described, together with methods of fault insertion. The hardware/software interface, including a restricted single error correction/double error detection (SEC/DED) code, is specified. Procedures are carefully described which, (1) test for specified physical faults, (2) ensure that single error corrections are not miscorrections due to triple faults, and (3) enable recovery from double errors.

  16. Pros and cons of the liposome platform in cancer drug targeting.

    PubMed

    Gabizon, Alberto A; Shmeeda, Hilary; Zalipsky, Samuel

    2006-01-01

    Coating of liposomes with polyethylene-glycol (PEG) by incorporation in the liposome bilayer of PEG-derivatized lipids results in inhibition of liposome uptake by the reticulo-endothelial system and significant prolongation of liposome residence time in the blood stream. Parallel developments in drug loading technology have improved the efficiency and stability of drug entrapment in liposomes, particularly with regard to cationic amphiphiles such as anthracyclines. An example of this new generation of liposomes is a formulation of pegylated liposomal doxorubicin known as Doxil or Caelyx, whose clinical pharmacokinetic profile is characterized by slow plasma clearance and small volume of distribution. A hallmark of these long-circulating liposomal drug carriers is their enhanced accumulation in tumors. The mechanism underlying this passive targeting effect is the phenomenon known as enhanced permeability and retention (EPR) which has been described in a broad variety of experimental tumor types. Further to the passive targeting effect, the liposome drug delivery platform offers the possibility of grafting tumor-specific ligands on the liposome membrane for active targeting to tumor cells, and potentially intracellular drug delivery. The pros and cons of the liposome platform in cancer targeting are discussed vis-à-vis nontargeted drugs, using as an example a liposome drug delivery system targeted to the folate receptor.

  17. Experimental system, and its evaluation for the control of surgically inducted infections

    NASA Technical Reports Server (NTRS)

    Tevebaugh, M. D.; Nelson, J. P.

    1972-01-01

    The effect is reported to design, fabricate, test and evaluate a prototype experimental system for the control of surgically induced infections. The purpose is to provide the cleanest possible environment within a hospital surgery room and eliminate contamination sources that could cause infections during surgery. The system design is described. The system provides for a portable laminar flow clean room, a full bubble helmet system with associated communications and ventilation subsystems for operating room personnel, and surgical gowns that minimize the migration of bacteria. The development test results consisting of portability, laminar flowrate, air flow pattern, electrostatic buildup, noise level, ventilation, human factors, electrical and material compatibility tests are summarized. The conclusions are that the experimental system is effective in reducing the airborne and wound contamination although the helmets and gowns may not be a significant part of this reduction. Definitive conclusions with regard to the infection rate cannot be made at this time.

  18. Enhancing Targeted Genomic DNA Editing in Chicken Cells Using the CRISPR/Cas9 System

    PubMed Central

    Wang, Ling; Yang, Likai; Guo, Yijie; Du, Weili; Yin, Yajun; Zhang, Tao; Lu, Hongzhao

    2017-01-01

    The CRISPR/Cas9 system has enabled highly efficient genome targeted editing for various organisms. However, few studies have focused on CRISPR/Cas9 nuclease-mediated chicken genome editing compared with mammalian genomes. The current study combined CRISPR with yeast Rad52 (yRad52) to enhance targeted genomic DNA editing in chicken DF-1 cells. The efficiency of CRISPR/Cas9 nuclease-induced targeted mutations in the chicken genome was increased to 41.9% via the enrichment of the dual-reporter surrogate system. In addition, the combined effect of CRISPR nuclease and yRad52 dramatically increased the efficiency of the targeted substitution in the myostatin gene using 50-mer oligodeoxynucleotides (ssODN) as the donor DNA, resulting in a 36.7% editing efficiency after puromycin selection. Furthermore, based on the effect of yRad52, the frequency of exogenous gene integration in the chicken genome was more than 3-fold higher than that without yRad52. Collectively, these results suggest that ssODN is an ideal donor DNA for targeted substitution and that CRISPR/Cas9 combined with yRad52 significantly enhances chicken genome editing. These findings could be extensively applied in other organisms. PMID:28068387

  19. Fabrication and characterization of carbon-backed thin 208Pb targets.

    PubMed

    Thakur, Meenu; Dubey, R; Abhilash, S R; Behera, B R; Mohanty, B P; Kabiraj, D; Ojha, Sunil; Duggal, Heena

    2016-01-01

    Thin carbon-backed isotopically enriched 208 Pb targets were required for our experiment aimed to study the reaction dynamics for 48 Ti +  208 Pb system, populating the near super-heavy nucleus 256 Rf, through mass-energy correlation of the fission fragments. Purity and thickness of the targets are of utmost importance in such studies as these factors have strong influence on the measurement accuracy of mass and energy distribution of fission fragments. 208 Pb targets with thickness ranging from 60 μg/cm 2 to 250 μg/cm 2 have been fabricated in high vacuum environment using physical vapor deposition method. Important points in the method are as follows: • 208 Pb was deposited using resistive heating method, whereas carbon (backing foil) deposition was performed by using the electron beam bombardment technique.•Different characterization techniques such as Particle Induced X-ray Emission (PIXE), Energy Dispersive X-Ray Fluorescence (EDXRF) and Rutherford Backscattering Spectrometry (RBS) were used to assert the purity and thickness of the targets.•These targets have successfully been used to accomplish our experimental objectives.

  20. High-Energy Space Propulsion Based on Magnetized Target Fusion

    NASA Technical Reports Server (NTRS)

    Thio, Y. C. F.; Landrum, D. B.; Freeze, B.; Kirkpatrick, R. C.; Gerrish, H.; Schmidt, G. R.

    1999-01-01

    Magnetized target fusion is an approach in which a magnetized target plasma is compressed inertially by an imploding material wall. A high energy plasma liner may be used to produce the required implosion. The plasma liner is formed by the merging of a number of high momentum plasma jets converging towards the center of a sphere where two compact toroids have been introduced. Preliminary 3-D hydrodynamics modeling results using the SPHINX code of Los Alamos National Laboratory have been very encouraging and confirm earlier theoretical expectations. The concept appears ready for experimental exploration and plans for doing so are being pursued. In this talk, we explore conceptually how this innovative fusion approach could be packaged for space propulsion for interplanetary travel. We discuss the generally generic components of a baseline propulsion concept including the fusion engine, high velocity plasma accelerators, generators of compact toroids using conical theta pinches, magnetic nozzle, neutron absorption blanket, tritium reprocessing system, shock absorber, magnetohydrodynamic generator, capacitor pulsed power system, thermal management system, and micrometeorite shields.

  1. National Ignition Facility: Experimental plan

    NASA Astrophysics Data System (ADS)

    1994-05-01

    As part of the Conceptual Design Report (CDR) for the National Ignition Facility (NIF), scientists from Lawrence Livermore National Laboratory (LLNL), Los Alamos National Laboratory (LANL), Sandia National Laboratory (SNL), the University of Rochester's Laboratory for Laser Energetics (UR/LLE), and EG&G formed an NIF Target Diagnostics Working Group. The purpose of the Target Diagnostics Working Group is to prepare conceptual designs of target diagnostics for inclusion in the facility CDR and to determine how these specifications impact the CDR. To accomplish this, a subgroup has directed its efforts at constructing an approximate experimental plan for the ignition campaign of the NIF CDR. The results of this effort are contained in this document, the Experimental Plan for achieving fusion ignition in the NIF. This group initially concentrated on the flow-down requirements of the experimental campaign leading to ignition, which will dominate the initial efforts of the NIF. It is envisaged, however, that before ignition, there will be parallel campaigns supporting weapons physics, weapons effects, and other research. This plan was developed by analyzing the sequence of activities required to finally fire the laser at the level of power and precision necessary to achieve the conditions of an ignition hohlraum target, and to then use our experience in activating and running Nova experiments to estimate the rate of completing these activities.

  2. TargetVue: Visual Analysis of Anomalous User Behaviors in Online Communication Systems.

    PubMed

    Cao, Nan; Shi, Conglei; Lin, Sabrina; Lu, Jie; Lin, Yu-Ru; Lin, Ching-Yung

    2016-01-01

    Users with anomalous behaviors in online communication systems (e.g. email and social medial platforms) are potential threats to society. Automated anomaly detection based on advanced machine learning techniques has been developed to combat this issue; challenges remain, though, due to the difficulty of obtaining proper ground truth for model training and evaluation. Therefore, substantial human judgment on the automated analysis results is often required to better adjust the performance of anomaly detection. Unfortunately, techniques that allow users to understand the analysis results more efficiently, to make a confident judgment about anomalies, and to explore data in their context, are still lacking. In this paper, we propose a novel visual analysis system, TargetVue, which detects anomalous users via an unsupervised learning model and visualizes the behaviors of suspicious users in behavior-rich context through novel visualization designs and multiple coordinated contextual views. Particularly, TargetVue incorporates three new ego-centric glyphs to visually summarize a user's behaviors which effectively present the user's communication activities, features, and social interactions. An efficient layout method is proposed to place these glyphs on a triangle grid, which captures similarities among users and facilitates comparisons of behaviors of different users. We demonstrate the power of TargetVue through its application in a social bot detection challenge using Twitter data, a case study based on email records, and an interview with expert users. Our evaluation shows that TargetVue is beneficial to the detection of users with anomalous communication behaviors.

  3. Texture-based measurement of spatial frequency response using the dead leaves target: extensions, and application to real camera systems

    NASA Astrophysics Data System (ADS)

    McElvain, Jon; Campbell, Scott P.; Miller, Jonathan; Jin, Elaine W.

    2010-01-01

    The dead leaves model was recently introduced as a method for measuring the spatial frequency response (SFR) of camera systems. The target consists of a series of overlapping opaque circles with a uniform gray level distribution and radii distributed as r-3. Unlike the traditional knife-edge target, the SFR derived from the dead leaves target will be penalized for systems that employ aggressive noise reduction. Initial studies have shown that the dead leaves SFR correlates well with sharpness/texture blur preference, and thus the target can potentially be used as a surrogate for more expensive subjective image quality evaluations. In this paper, the dead leaves target is analyzed for measurement of camera system spatial frequency response. It was determined that the power spectral density (PSD) of the ideal dead leaves target does not exhibit simple power law dependence, and scale invariance is only loosely obeyed. An extension to the ideal dead leaves PSD model is proposed, including a correction term to account for system noise. With this extended model, the SFR of several camera systems with a variety of formats was measured, ranging from 3 to 10 megapixels; the effects of handshake motion blur are also analyzed via the dead leaves target.

  4. Experimental Evaluation of the Training Structure of the Picture Exchange Communication System (PECS)

    ERIC Educational Resources Information Center

    Cummings, Anne R.; Carr, James E.; LeBlanc, Linda A.

    2012-01-01

    The Picture Exchange Communication System (PECS) is a picture-based alternative communication method that is widely accepted and utilized with individuals with disabilities. Although prior studies have examined the clinical efficacy of PECS, none have experimentally evaluated its manualized training structure. We experimentally evaluated the…

  5. Through-the-Wall Localization of a Moving Target by Two Independent Ultra Wideband (UWB) Radar Systems

    PubMed Central

    Kocur, Dušan; Švecová, Mária; Rovňáková, Jana

    2013-01-01

    In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered. PMID:24021968

  6. Through-the-wall localization of a moving target by two independent ultra wideband (UWB) radar systems.

    PubMed

    Kocur, Dušan; Svecová, Mária; Rovňáková, Jana

    2013-09-09

    In the case of through-the-wall localization of moving targets by ultra wideband (UWB) radars, there are applications in which handheld sensors equipped only with one transmitting and two receiving antennas are applied. Sometimes, the radar using such a small antenna array is not able to localize the target with the required accuracy. With a view to improve through-the-wall target localization, cooperative positioning based on a fusion of data retrieved from two independent radar systems can be used. In this paper, the novel method of the cooperative localization referred to as joining intersections of the ellipses is introduced. This method is based on a geometrical interpretation of target localization where the target position is estimated using a properly created cluster of the ellipse intersections representing potential positions of the target. The performance of the proposed method is compared with the direct calculation method and two alternative methods of cooperative localization using data obtained by measurements with the M-sequence UWB radars. The direct calculation method is applied for the target localization by particular radar systems. As alternative methods of cooperative localization, the arithmetic average of the target coordinates estimated by two single independent UWB radars and the Taylor series method is considered.

  7. Cognitive Mechanisms of Change in Delusions: An Experimental Investigation Targeting Reasoning to Effect Change in Paranoia

    PubMed Central

    Garety, Philippa; Waller, Helen; Emsley, Richard; Jolley, Suzanne; Kuipers, Elizabeth; Bebbington, Paul; Dunn, Graham; Fowler, David; Hardy, Amy; Freeman, Daniel

    2015-01-01

    Background: Given the evidence that reasoning biases contribute to delusional persistence and change, several research groups have made systematic efforts to modify them. The current experiment tested the hypothesis that targeting reasoning biases would result in change in delusions. Methods: One hundred and one participants with current delusions and schizophrenia spectrum psychosis were randomly allocated to a brief computerized reasoning training intervention or to a control condition involving computer-based activities of similar duration. The primary hypotheses tested were that the reasoning training intervention, would improve (1) data gathering and belief flexibility and (2) delusional thinking, specifically paranoia. We then tested whether the changes in paranoia were mediated by changes in data gathering and flexibility, and whether working memory and negative symptoms moderated any intervention effects. Results: On an intention-to-treat analysis, there were significant improvements in state paranoia and reasoning in the experimental compared with the control condition. There was evidence that changes in reasoning mediated changes in paranoia, although this effect fell just outside the conventional level of significance after adjustment for baseline confounders. Working memory and negative symptoms significantly moderated the effects of the intervention on reasoning. Conclusion: The study demonstrated the effectiveness of a brief reasoning intervention in improving both reasoning processes and paranoia. It thereby provides proof-of-concept evidence that reasoning is a promising intermediary target in interventions to ameliorate delusions, and thus supports the value of developing this approach as a longer therapeutic intervention. PMID:25053650

  8. AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis

    PubMed Central

    Castañeda, Ximena; García-de-la-Mària, Cristina; Gasch, Oriol; Pericas, Juan M.; Armero, Yolanda; Soy, Dolors; García-González, Javier; Falces, Carlos; Ninot, Salvador; Almela, Manel; Ambrosioni, Juan; Quintana, Eduardo; Vidal, Barbara; Fuster, David; Llopis, Jaume; Soto, Sara; Moreno, Asuncion; Marco, Francesc

    2017-01-01

    ABSTRACT The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) (P = 0.343), while the medians (interquartile ranges [IQRs]) for log10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) (P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis. PMID:28373187

  9. AUC/MIC Pharmacodynamic Target Is Not a Good Predictor of Vancomycin Efficacy in Methicillin-Resistant Staphylococcus aureus Experimental Endocarditis.

    PubMed

    Castañeda, Ximena; García-de-la-Mària, Cristina; Gasch, Oriol; Pericas, Juan M; Armero, Yolanda; Soy, Dolors; García-González, Javier; Falces, Carlos; Ninot, Salvador; Almela, Manel; Ambrosioni, Juan; Quintana, Eduardo; Vidal, Barbara; Fuster, David; Llopis, Jaume; Soto, Sara; Moreno, Asuncion; Marco, Francesc; Miró, Jose M

    2017-06-01

    The aim of this in vivo study was to compare the efficacy of vancomycin at standard doses (VAN-SD) to that of VAN at adjusted doses (VAN-AD) in achieving a VAN area under the curve/MIC ratio (AUC/MIC) of ≥400 against three methicillin-resistant Staphylococcus aureus (MRSA) strains with different microdilution VAN MICs in an experimental endocarditis model. The valve vegetation bacterial counts after 48 h of VAN therapy were compared, and no differences were observed between the two treatment groups for any of the three strains tested. Overall, for VAN-SD and VAN-AD, the rates of sterile vegetations were 15/45 (33.3%) and 21/49 (42.8%) ( P = 0.343), while the medians (interquartile ranges [IQRs]) for log 10 CFU/g of vegetation were 2 (0 to 6.9) and 2 (0 to 4.5) ( P = 0.384), respectively. In conclusion, this VAN AUC/MIC pharmacodynamic target was not a good predictor of vancomycin efficacy in MRSA experimental endocarditis. Copyright © 2017 American Society for Microbiology.

  10. An Integrated Computational and Experimental Approach Toward the Design of Materials for Fuel Cell Systems

    DTIC Science & Technology

    2012-10-01

    13 Based on the limited work done, the best reported ORR chalcogenide electrocatalysts for PEMFC applications can be ranked as follows: MoRuSe... PEMFC catalysts is the durability of the catalyst particles. Particle size distribution tends to shift towards larger particles during the...the design of new materials for applications in PEMFCs . Reference: A more detailed treatment of the topics of this section, Experimental Target 11

  11. Optical Investigations of Powerful Laser Actions on Massive and Flyer Targets

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

    Pisarczyk, T.; Borodziuk, S.; Kasperczuk, A.

    2006-01-15

    In this paper we present experimental, theoretical, and computer simulation studies of craters formation produced by high power lasers in single and double layer targets. The experimental investigation was carried out using the PALS (Prague Asterix Laser System) facility working with two different laser beam wavelengths: {lambda}1 = 1.315 {mu}m and {lambda}3 0.438 {mu}m. Two types of targets made of Al were used: single massive targets, and double targets consisting of a foil or disk (6 {mu}m thick for both cases) placed in front of the massive target part at a distance of 200-500 {mu}m. Experiments with single massive targetsmore » were performed at laser intensities in the range of 1013-1015 W/cm2 by varying the laser beam diameters on the target surface from 70 {mu}m up to 1200 {mu}m (i.e. moving the target away from the focus). The double targets were illuminated by laser energies EL = 100-500 J focused always on a diameter of 250 {mu}m. In all experiments performed the laser pulse duration was equal to 400 ps. 3-frame interferometry was employed to investigate the plasma dynamics through measurements of the electron density distribution time development as well as of the disks and foil fragments velocities. The dimensions and shapes of craters were obtained by crater replica technology and microscopy measurement. The experiments were complemented by a 2-D analytical theory and computer simulations, which helped at interpretation of the results. This way the values of laser energy absorption coefficient, ablation loading efficiency and efficiency of energy transfer, as well as two-dimensional shock wave generation at the laser-driven macroparticle impact were obtained from the measured crater parameters for both the wavelengths of laser radiation.« less

  12. Morphological Effect of Non-targeted Biomolecule-Modified MNPs on Reticuloendothelial System

    NASA Astrophysics Data System (ADS)

    Li, Xiao; Hu, Yan; Xiao, Jie; Cheng, Dengfeng; Xiu, Yan; Shi, Hongcheng

    2015-09-01

    Magnetic nanoparticles (MNPs) with special morphology were commonly used as biomaterials, while morphological effects of non-targeted biomolecule-modified MNPs on biological behaviors were still unclear. In this research, spherical and rod-like Fe3O4 in a comparable size were synthesized and then surface-modified by bovine serum albumin (BSA) as a model of non-targeted biomolecule-modified MNPs. Morphological effects were featured by TEM and quantification of in vitro phagocytic uptake, as well as the in vivo quantification of particles in reticuloendothelial system (RES)-related organs of normal Kunming mice. For these non-targeted BSA-modified MNPs, intracellular distributions were the same, but the rod-like MNPs were more likely to be uptake by macrophages; furthermore, the BSA-modified MNPs gathered in RES-related organs soon after intravenous injection, but the rod-like ones were expelled from the lung more quickly and expelled from the spleen more slowly. These preliminary results may be referable if MNPs or other similar biomolecule-modified nanoparticles were used.

  13. Assessment, Target Selection, and Intervention: Dynamic Interactions within a Systemic Perspective

    ERIC Educational Resources Information Center

    Williams, A. Lynn

    2005-01-01

    There are a number of clinical options available for speech-language pathologists to choose from to analyze a child's phonological system, select treatment targets, and design intervention. Frequently, each of these areas of clinical options is viewed independently of one another or approached within an eclectic framework. In this article, an…

  14. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs.

    PubMed

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J; Fogel, Wieslawa A; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of "one-molecule-one-target," have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders.

  15. Monoaminergic Mechanisms in Epilepsy May Offer Innovative Therapeutic Opportunity for Monoaminergic Multi-Target Drugs

    PubMed Central

    Svob Strac, Dubravka; Pivac, Nela; Smolders, Ilse J.; Fogel, Wieslawa A.; De Deurwaerdere, Philippe; Di Giovanni, Giuseppe

    2016-01-01

    A large body of experimental and clinical evidence has strongly suggested that monoamines play an important role in regulating epileptogenesis, seizure susceptibility, convulsions, and comorbid psychiatric disorders commonly seen in people with epilepsy (PWE). However, neither the relative significance of individual monoamines nor their interaction has yet been fully clarified due to the complexity of these neurotransmitter systems. In addition, epilepsy is diverse, with many different seizure types and epilepsy syndromes, and the role played by monoamines may vary from one condition to another. In this review, we will focus on the role of serotonin, dopamine, noradrenaline, histamine, and melatonin in epilepsy. Recent experimental, clinical, and genetic evidence will be reviewed in consideration of the mutual relationship of monoamines with the other putative neurotransmitters. The complexity of epileptic pathogenesis may explain why the currently available drugs, developed according to the classic drug discovery paradigm of “one-molecule-one-target,” have turned out to be effective only in a percentage of PWE. Although, no antiepileptic drugs currently target specifically monoaminergic systems, multi-target directed ligands acting on different monoaminergic proteins, present on both neurons and glia cells, may represent a new approach in the management of seizures, and their generation as well as comorbid neuropsychiatric disorders. PMID:27891070

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

    PubMed

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

    2018-01-01

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

  17. Delivery of drugs to intracellular organelles using drug delivery systems: Analysis of research trends and targeting efficiencies.

    PubMed

    Maity, Amit Ranjan; Stepensky, David

    2015-12-30

    Targeting of drug delivery systems (DDSs) to specific intracellular organelles (i.e., subcellular targeting) has been investigated in numerous publications, but targeting efficiency of these systems is seldom reported. We searched scientific publications in the subcellular DDS targeting field and analyzed targeting efficiency and major formulation parameters that affect it. We identified 77 scientific publications that matched the search criteria. In the majority of these studies nanoparticle-based DDSs were applied, while liposomes, quantum dots and conjugates were used less frequently. The nucleus was the most common intracellular target, followed by mitochondrion, endoplasmic reticulum and Golgi apparatus. In 65% of the publications, DDSs surface was decorated with specific targeting residues, but the efficiency of this surface decoration was not analyzed in predominant majority of the studies. Moreover, only 23% of the analyzed publications contained quantitative data on DDSs subcellular targeting efficiency, while the majority of publications reported qualitative results only. From the analysis of publications in the subcellular targeting field, it appears that insufficient efforts are devoted to quantitative analysis of the major formulation parameters and of the DDSs' intracellular fate. Based on these findings, we provide recommendations for future studies in the field of organelle-specific drug delivery and targeting. Copyright © 2015 Elsevier B.V. All rights reserved.

  18. A graphene oxide based smart drug delivery system for tumor mitochondria-targeting photodynamic therapy

    NASA Astrophysics Data System (ADS)

    Wei, Yanchun; Zhou, Feifan; Zhang, Da; Chen, Qun; Xing, Da

    2016-02-01

    Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in organic and aqueous environments, respectively. The PPa-NGO-mAb assembly is able to effectively target the αvβ3-positive tumor cells with surface ligand and receptor recognition; once endocytosized by the cells, they are observed escaping from lysosomes and subsequently transferring to the mitochondria. In the mitochondria, the `on' state PPa-NGO-mAb performs its effective phototoxicity to kill cells. The biological and physical dual selections and on/off control of PPa-NGO-mAb significantly enhance mitochondria-mediated apoptosis of PDT. This smart system offers a potential alternative to drug delivery systems for cancer therapy.Subcellular organelles play critical roles in cell survival. In this work, a novel photodynamic therapy (PDT) drug delivery and phototoxicity on/off nano-system based on graphene oxide (NGO) as the carrier is developed to implement subcellular targeting and attacking. To construct the nanodrug (PPa-NGO-mAb), NGO is modified with the integrin αvβ3 monoclonal antibody (mAb) for tumor targeting. Pyropheophorbide-a (PPa) conjugated with polyethylene-glycol is used to cover the surface of the NGO to induce phototoxicity. Polyethylene-glycol phospholipid is loaded to enhance water solubility. The results show that the phototoxicity of PPa on NGO can be switched on and off in

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

    NASA Astrophysics Data System (ADS)

    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

  20. Challenging the state of the art in protein structure prediction: Highlights of experimental target structures for the 10th Critical Assessment of Techniques for Protein Structure Prediction Experiment CASP10.

    PubMed

    Kryshtafovych, Andriy; Moult, John; Bales, Patrick; Bazan, J Fernando; Biasini, Marco; Burgin, Alex; Chen, Chen; Cochran, Frank V; Craig, Timothy K; Das, Rhiju; Fass, Deborah; Garcia-Doval, Carmela; Herzberg, Osnat; Lorimer, Donald; Luecke, Hartmut; Ma, Xiaolei; Nelson, Daniel C; van Raaij, Mark J; Rohwer, Forest; Segall, Anca; Seguritan, Victor; Zeth, Kornelius; Schwede, Torsten

    2014-02-01

    For the last two decades, CASP has assessed the state of the art in techniques for protein structure prediction and identified areas which required further development. CASP would not have been possible without the prediction targets provided by the experimental structural biology community. In the latest experiment, CASP10, more than 100 structures were suggested as prediction targets, some of which appeared to be extraordinarily difficult for modeling. In this article, authors of some of the most challenging targets discuss which specific scientific question motivated the experimental structure determination of the target protein, which structural features were especially interesting from a structural or functional perspective, and to what extent these features were correctly reproduced in the predictions submitted to CASP10. Specifically, the following targets will be presented: the acid-gated urea channel, a difficult to predict transmembrane protein from the important human pathogen Helicobacter pylori; the structure of human interleukin (IL)-34, a recently discovered helical cytokine; the structure of a functionally uncharacterized enzyme OrfY from Thermoproteus tenax formed by a gene duplication and a novel fold; an ORFan domain of mimivirus sulfhydryl oxidase R596; the fiber protein gene product 17 from bacteriophage T7; the bacteriophage CBA-120 tailspike protein; a virus coat protein from metagenomic samples of the marine environment; and finally, an unprecedented class of structure prediction targets based on engineered disulfide-rich small proteins. Copyright © 2013 The Authors. Wiley Periodicals, Inc.